PATHOLOGY

I EXERCISE
HISTOPATHOLOGICAL FEATURES OF BASIC INJURY OF CELLS AND
EXTRACELLULAR MATRIX

1. ATROPHIA ET SCLEROSIS TESTIS (Testicular atrophy with sclerosis)

Histologic changes are characterized by considerable atrophy of germ cells associated
with marked hyalinization and thickening of the basement membrane of the spermatic tubules.
Eventually the tubules are visible as shadow structures or dense cords of hyaline connective
tissue. Sertoli cells may be intact along the tubular basement membrane. There may be
concomitant increase in interstitial stroma and usually some hyperplasia of Leydig cells.

2. ATROPHIA FUSCA HEPATIS (Brown atrophy of the liver)

The cytoplasm of atrophied hepatocytes is crowded with fine, yellow-brown granules
of pigment lipofuscin. Pigment granules are located near the nucleus of atrophied cells. Mainly
centrolobular hepatocytes are altered in this way.

3. AMYLOIDOSIS RENIS (Renal amyloidosis)

The selective sites of amyloid involvement are primarily the glomeruli, but the
interstitial peritubular tissue, arteries, and arterioles are also affected.
The glomerular deposits first appear as subtle thickenings of the mesangial matrix,
accompanied usually by widening of the basement membrane of the glomerular capillaries. In
time, these deposits cause capillary narrowing and distortion of the glomerular vascular tuft.
With progression of the glomerular amyloidosis, the endothelial cells are enveloped, the
capillary lumina are obliterated, and the obsolescent glomerulus is flooded by confluent masses
or interlacing broad ribbons of amyloid.
The peritubular deposits also begin in apposition to the tubular basement membranes
and extend progressively into the intertubular connective tissue as well as encroach on the
tubular lumina. The overlying tubular epithelium may be unaffected or may undergo regressive
changes. Often, proteinaceous casts fill these tubular lumina.
The vascular involvement takes the form of pink, hyaline thickening of arterial and
arteriolar walls, often with narrowing of the lumina. With such ischaemia, widespread tubular
atrophy and interstitial fibrosis superimpose themselves upon the basic deformity produced by
the amyloidosis.

4. AMYLOIDOSIS LIENIS (Amyloidosis of the spleen)

It is believed that the amyloid deposits begin in the perifollicular regions, and later the
deposits are far more widespread. For completely mysterious reasons, one of two patterns
emerges.
In one the deposit is largely limited to the splenic follicles, producing tapioca-like
granules on gross inspection, designated "sago spleen". Histologically, the entire follicle may
be replaced in advanced cases. The coalescent masses of amyloid surround the spleen cells.
In the other pattern, the amyloid appears to spare the follicles and instead involves the
walls of the splenic sinuses and connective tissues framework in the red pulp. Fusion of the
early deposits gives rise to large, maplike areas of amyloidosis, creating what has been
designated the "lardaceous" spleen.
 5. HYALINOSIS VASORUM LIENIS (Hyalinosis of the blood vessels)

The selective sites of hyaline involvement are central arteries and penicilliary arterioles.
They have homogenous, amorphous, pink, hyaline thickening of their walls with loss of
underlying structural detail (compressible atrophy of smooth muscle cells in the media) and
with narrowing of the lumen. In time, lymphoid cells in splenic follicles are rarefied.

6. INFILTRATIO ADIPOSA MYOCARDII

(Fatty ingrowth of the myocardium)

Fatty ingrowth or stromal fatty infiltration implies appearance of adult adipose cells
within the connective tissue stroma. In the heart, the right ventricle is generally more severely
affected than the left. Usually, there is an increase of subepicardial fat that extends in continuity
as finger-like projections between the muscle bundles. The adult fat cells usually only separate
the adjacent myocardial cells. In advanced cases, muscle cells may be even compressibly
atrophied.

7. METAMORPHOSIS ADIPOSA HEPATIS DIFFUSA

(Fatty change of the liver)

Fatty change begins with the development of minute, membrane-bound inclusions

(liposomes) closely applied to the endoplasmic reticulum. It is first manifested light
microscopically by the appearance of small fat vacuoles in the cytoplasm of hepatocytes around
the nucleus. As the process progresses, the vacuoles coalesce to create cleared spaces that
displace the nucleus to the periphery of the cell. Occasionally, contiguous cells rupture, and the
enclosed fat globules coalesce to produce so-called fatty cysts.

II EXERCISE
HISTOPATHOLOGICAL FEATURES CIRCULATORY DISORDERS

8. HYPERAEMIA PASSIVA PULMONIS CHRONICA (HAEMOSIDEROSIS

PULMONUM)
Chronic passive congestion of the lung (Pulmonary hemosiderosis)

In chronic venous congestion of the lung the pulmonary capillaries are distended and
red blood cells have escaped from the vessels into the lumen of the alveoli. Pulmonary
macrophages are activated for fagocytosis of these red blood cells. The net result of the
digestion is haemosiderin pigment (brown-black) wihtin alveolar macrophages. Haemosiderin
can heavily laden these cells that we call haemosiderophages or “heart failure cells”.
 9. NECROSIS HEPATIS CENTRALIS HAEMORRHAGICA
(Central hemorrhagic necrosis of the liver)

Sometimes, rupture of the capillary sinusoids may cause hemorrhage into the hepatic
cords with subsequent acute necrosis of the centrolobullary located hepatocytes. Centrolobular
necrosis is a characteristic of ischemic injury. Left-sided cardiac failure or shock may lead to
hepatic hypoperfusion and ischemic injury. In this instance hepatocytes in the central region of
the lobule undergo ischaemic necrosis. The combination of hypoperfusion and retrograde
congestion act synergistically to generate centrolobular hemorrhagic necrosis. Centrolobular
necrosis is visible microscopically as a sharp demarcation of viable and necrotic hepatocytes.
Necrotic area is intensively red in color because of the red cytoplasm of necrotic hepatocytes
which lack the muclei.

10. HYPERAEMIA PASSIVA LIENIS CHRONICA

(Chronic passive congestion of the spleen)

Chronic passive congestion of the spleen is associated with chronic passive congestion
of the liver. The most common causes of congestive splenomegaly are the various forms of
cirrhosis of the liver.
Microscopically, marked sinusoidal dilatation is seen and it is accompanied by foci of
recent hemorrhage and sometimes hemosiderin deposits. Fibrous thickening of the edematous
congested sinusoidal walls, diffuse fibrosis and hemosiderin deposition produce the
characteristic anatomic pattern of congestive splenomegaly.
The pulp is suffused with red cells during the early phases but it becomes increasingly
more fibrous and cellular with time. The walls of the venous sinuses are thickened and cellular,
and the space between them is filled with proliferated fibroblasts or reticuloendothelial cells.

11. THROMBUS VENAE IN ORGANISATIONE

(Oganization of the venous thrombus)

The formation of a blood coagulum within a vessel or the heart is known as thrombosis,
and the clot is referred to a thrombus.
Venous lumen is almost totally occluded. The thrombus is attached to the venous wall. The
thrombus contains fibrin, manifested as red fibers and cells – granulocytes and erytrocytes.
Fibroblasts and capillary buds invade thrombus from the underlying venous wall. The
endothelial cells at the attached margin of the thrombus grow out over the surface of the
thrombus and cover exposed areas with a continuous endothelium.

12. INFARCTUS ANAEMICUS RENIS

(White – anemic - infarct of the kidney)

Infarct of the kidney is of the anemic type, because the arterial supply to the kidney is
essentially of the “end-organ” type. Renal infarction is presented as wedge shaped, with the
shadowy outlines of necrotic renal tissue (coagulative necrosis of glomeruli, tubuli, blood
vessels and interstitium). Blood vessels near the infarcted zone are distended with the blood,
and tissue at the border of infarcted zone is infiltrated with numerous granulocytes.
 13. INFARCTUS HAEMORRHAGICUS PULMONIS
(Hemorrhagic infarct of the lung)

Pulmonary emboli cause infarction when the circulation is previously inadequate. The
pulmonary infarct is classically hemorrhagic.The diagnostic feature of pulmonary infarction is
the ischaemic necrosis of the lung tissue with the superimposed hemorrhage. Such necrosis
affects not only the alveolar walls, but the interstitial tissue, bronchioles and vessels. The red
blood cells are intermingled with the necrotic tissue and present in the alveolar space. The
inflammatory reaction (granulocytes) at the margins represents demarcation of an area of
necrotic tissue.

III EXERCISE –
HISTOPATHOLOGICAL FEATURES OF INFLAMMATION
,

14. PLEURITIS FIBRINOSO-PURULENTA

(Fibrinous-purulent pleuritis)

During the inflammatory process in the lung-named pneumonia, inflammatory exudate

can spread to the pleural surface. The acute phase of inflammation is characterized with fibrin
deposition (it is a plasma protein). Fibrinous exudate presents in the form of pink, eosinophilic
stained extracellular material. Neutrophils are present in high number within the fibrinous
exudate, hence the term: “fibrinosopurulenta” (fibrinous-purulent).

15. ABSCESSUS HEPATIS

(Liver abscess)

An abscessus is an ovoid shaped collection of pus that replaces the tissue defect due to
necrosis of tissue cells caused by pyogenic microorganisms. The pus is composed of necrotic
tissue cells, dead and viable polymorphonuclear leukocytes and pyogenic microorganisms. The
liver tissue adjacent to the abscess is compressed. If the process is of longer duration, it is the
chronic abscessus: the liver tissue adjacent to the abscessus is replaced with granulation tissue
that mature to fibrous tissue.

16. PHLEGMONE CUTIS

(Phlegmone of the skin)

This is a type of acute purulent inflammation in which the inflammatory infiltrate is

composed predominantly of polymorphonuclear leukocytes infiltrating in a diffuse pattern all
layers of the skin. There are many polymorphonuclear leukocytes in the dermis. Blood vessels
are dilated enormously and an almost continuos layer of polymorphonuclear leukocytes is
adhaerent to the endothelial surface (leucostasis). Large areas of tissue necrosis may be present.
17. APPENDICITIS PHLEGMONOSA
(Phlegmonose appendicitis)

In this inflammatory process in appendix, all layers of appendix wall are affected with
inflammation and only few remnants of mucosa can be recognised. The full thickness of the
appendiceal wall is diffusely infiltrated with polymorphonuclear leukocytes. The lumen of
appendix can be filled with inflammatory exudate with necrotic cells and polymorphonuclear
leukocytes.

18. LYMPHADENITIS TUBERCULOSA

(Tuberculous lymphadenitis)

The normal architecture of the lymph node is disrupted with several granulomas called
tubercles that can be sometimes fussed without clear borders. Granulomas are rounded
structures containing macrophages. The centre of tubercle contains caseous necrosis, granular
and eosinophilic in appearance. Epitheloid cells are present around caseous necrosis. These
cells are transformed macrophages. Epithelioid cells are small, elongated, thin cells, containing
red cytoplasms and small dark nuclei. These cells resemble somewhat epithelial cells, hence
the name. The multinucleated giant cells of Langhans type can be present. Numerous nuclei are
dispersed in a horse shoe pattern. At the periphery of the tubercles, lymphocytes are present (in
the lymph node, not easily distinguished from the normal lymphocytes).

19. CYSTICERCOSIS CEREBRI

(Cerebral cysticercosis)

Cerebral cysticercosis is produced by the larvae of the pork tapeworm, Taenia solium,
named cysticercus cellulosae. The cyst wall has three histologically distinct layers: a corrugated
cuticular layer with hairlike protrusions in contact with host tissue, a thin middle cellular layer,
and a thick inner layer containing a loosely packed network of small canaliculi. Little tissue
reaction is seen around the cyst unless the larva dies, in which case the cyst wall becomes
permeable producing a severe acute inflammatory reaction, sometimes associated with foreign
body giant cells.

20. GRANULOMA CORPORIS ALIENI

(Foreign body type granuloma)

This is a characteristic form of granulomatous chronic inflammation caused by presence

of foreign materials of exogenous (glass particles, surgical threads, etc.) or endogenous origin
(like keratin from ruptured epidermoid cyst). Granuloma consists of macrophages,
multinucleated giant cells – foreign body type (with haphazardly arrangement of nuclei) with a
collar of lymphocytes and occasionally plasma cells. The foreign body material is sometimes
not present within the foreing body granuloma.
IV EXERCISE -
HISTOPATHOLOGICAL FEATURES OF BENIGN AND MALIGNANT TUMORS

21. PAPILLOMA MUCOSAE ORIS

(Papilloma of the oral mucosa )

Benign verrucous tumor lined by hyperplastic squamous epithelium. Histologically, this

tumor consists of proliferation of stratified squamous epithelium supported by a fibrous stroma.
Acanthosis (epidermal hyperplasia), parakeratosis (mode of keratinization characterized by the
retention of nuclei in the stratum corneum), hyperkeratosis (hyperplasia of stratum corneum)
and a peculiar vacuolization of epithelial cells (called koilocytosis) are often present.

22. POLYPUS CERVICIS UTERI

(Cervical polyp)

Endocervical polyps are common inflammatory (pseudo) tumors, frequently associated

with chronic cervicitis. All are soft, almost mucoid, and microscopically composed of a loose
fibromyxomatous stroma and cystically dilated, mucus-secreting endocervical glands.

23. ADENOMA TUBULARE (POLYPUS ADENOMATOSUS) INTESTINI COLI

(Adenomatous polyp = Tubular adenoma of the colon)

A polyp is a structure that protrudes into the lumen of a hollow organ above the
surrounding mucosa. It may be pedunculated or sessile.
Tubular adenoma is composed of neoplastic crypts, resembling normal tubules, i.e. crypts
(glands) of the colonic mucosa, hence the term “tubular”. These glands are proliferated,
crowded and disorganized contributing to a polypoid mass. Neoplastic tubules are lined by
pseudostratified epithelium. It exhibits the following features: the cell cytoplasm is
eosinophilic, and the nuclei are elongated, dark and pointed. The nuclei are placed in several
levels along the epithelium of the neoplastic crypt. There is the depletionf of the goblet cells.
Accumulation of additional mutations over time and with continued growth of adenoma may
give rise to malignant transformation into colonic adenocarcinoma.

24. MALIGNANT CELLS IN CYTOLOGICAL SMEARS

Lack of differentiation or anaplasia is marked by a number of morphologic and

functional changes. Both, the cells and their nuclei display pleomorphism - variation in the size
and shape. The nuclei contain an abundance of DNA and are extremely dark (hyperchromatic).
The nuclear-cytoplasmic ratio may approach 1:1 instead of the normal 1:4 or 1:6. Large nucleoli
are usually present in these nuclei. Another important feature of anaplasia is the formation of
tumor giant cells, some possessing only a single huge polymorphic nucleus, while others have
two or more nuclei.
25. HSIL CERVICIS UTERI
(Cervical High grade Squamous Intraepithelial Lesion = HSIL)

There is severe cervical squamous dysplasia on this slide.

Note how the dysplastic cell nuclei are larger and darker, and the dysplastic cells have a
disorderly arrangement within the epithelium. The dysplasia involves the full thickness of the
epithelium, but the basal lamina is intact. Designations of both severe dysplasia and carcinoma
in situ (CIS) fall under the Cervical Intraepithelial Neoplasia (CIN). Dysplasia affecting the full
thickness of the epithelimu is High-grade Squamous Intraepithelial Lesion (HSIL) and have the
greatest risk for progression to invasive carcinoma, which means invasion through the basal
lamina.

26. INVASIVE SQUAMOUS CELL CARCINOMA OF UTERINE CERVIX

Irregulary shaped nests of squamous cell carcinoma are invading downward, beneath
the basal lamina, and undermining the mucosa, through a chronically inflammed stroma.
Most cervical squamous cell carcinomas are composed of large pink keratinizing or non-
keratinizing squamous cells. These cells are large, polygonal and pleomorphic with large
hyperchromatic nuclei. Squamous cell carcinoma is well differentiated if there is formation of
keratin pearls within the nests of tumor cells.

27. ADENOCARCINOMA PULMONIS

(Pulmonary adenocarcinoma)

Cancer is the common term for all malignant tumors. Malignant tumors of epithelial cell
origin derived from any of the three germ layers are called carcinomas. Carcinomas with a
microscopically glandular growth pattern, or originating from glandular tissue - are termed
adenocarcinomas. (Cancers originating from mesenchymal tissue are called sarcomas)
The glandular structures in adenocarcinoma are malignant glands. Malignant gland are
irregular in shape and size. They are lined by malignant epithelium which exhibits pleomorphic
nuclei. The nuclei in malignant gland lost their normal basal position, and could be seen in all
levels of glandular epithelium. Prominent nucleoli are often present. Droplets of mucin may be
found within the tumor cell cytoplasm.
The malignant glands in this neoplasm are consistent with a moderately differentiated
adenocarcinoma. Bronchial wall cartilage is present in this slide.

28. CARCINOMA METASTATICUM IN MEDULLA OSSIS

(Metastatic carcinoma to the bone marrow)

Within the bone marrow, malignant glands seen as glandular/tubular lumina lined by
malignant atypical cuboidal epithelial cells and cords/nests of similar cells refer as metastazing
adenocarcinoma. It is a space-occupying lesions in the bone marrow. Metastatic
adenocarcinoma destroys normal hematopoietic cells and the bone marrow architecture.
29. CARCINOMA METASTATICUM IN NODO LYMPHATICO
(Metastatic carcinoma to the lymph node)

The glandular structures seen as glandular/tubular lumina lined by malignant atypical

cuboidal epithelial cells and cords/nests of similar cells are present within the lymph node. This
adenocarcinomatous tissue within the lymph node refers as metastazing adenocarcinoma to the
lymph node.

HISTOPATHOLOGICAL FEATURES OF CARDIOVASCULAR DISEASES

30. MYOFIBROSIS CORDIS (Fibrosis of the myocardium)

The number of cardiac muscle fibers is reduced. The surviving muscle fibers appear
hypertrophied. The amount of fibrous tissue between cardiomyocytes is larger than normal.
Usually, this condition is caused by chronic ischemia.

31. MYOCARDITIS VIROSA (Viral Myocarditis)

Myocarditis is characterized by morphological changes indicative of an inflammatory

reaction, usually due to a microbiologic agent. It is an important form of heart disease because
it may occur at any age, even in infancy. Occasionally with unexpected suddenness myocarditis
may induce cardiac failure or cause sudden death by arrhythmia. The causes of myocarditis
include virtually every known microbiologic agent, various forms of immunologically mediated
damage, hypersensitivity reactions and reactions to physical agents. Viral agents include:
Coxsackie A and B, ECHO virus, influenza, poliomyelitis, viral hepatitis, Epstein-Barr
(infectious mononucleosis), cytomegalovirus. During the active phase of myocarditis the heart
is usually enlarged with dilatation of all chambers, but only the left or right ventricle.
Histologically, a mononuclear inflammatory infiltrate, consisting of lymphocytes and
hystiocytes, is diffusely positioned within the interstitium. Isolated myofiber lysis
(myocytolysis) or patchy foci of cardiomyocyte necrosis may be present. There is no large
areas of myocardial necrosis, seen in acute myocardial infarction.
32. NEPHROCIRRHOSIS ARTERIO ET ARTERIOLOSCLEROTICA
Synonym: Benign nephrosclerosis

Benign nephrosclerosis is the term used for the lesion of the kidney in benign
hypertension. It is always associated with hyaline arteriolosclerosis.
Histologically, thickening and hyalinization of the walls of arterioles and small arteries cause
the narrowing of the lumina. It is thought that the hyaline material is composed in large part of
plasma proteins and lipids that have leaked from the vessel lumen into the vessel wall and
precipitated within the vessel wall, probably because of endothelial injury. Consequent to the
hyaline vascular narrowing, there is patchy ischemic injury, which consists of: foci of tubular
atrophy and interstitial fibrosis and a variety of glomerular alterations. The latter include
collapse of glomerular basement membranes, deposition of collagen within Bowman’s space,
periglomerular fibrosis and total sclerosis of glomeruli. In general, the severity of the ischemia
parallels that of the vascular changes.

33. ATHEROSCLEROSIS AORTAE (Atherosclerosis of the aorta)

Atherosclerosis is a disease of large and medium-sized muscular arteries (e.g. coronary,

carotid, arteries of lower extremities) and large elastic arteries, such as the aorta and iliac
vessels. The basic lesion is atheroma, or a core of lipid (mainly cholesterol usually complexed
with proteins and cholesterol esters), or atherosclerotic plaque, consisting of lipid material and
a covering fibrous cap. Plaques are white to yellow in appearance, protrude into the lumen of
the artery.
Histologically, atherosclerotic plaques are localized in intima and are composed of a
superficial part (the fibrous cap) made up of collagen in which there are variable numbers of
smooth muscle cells, and a deeper or central part in which there is a disorganized mass of lipid
material, cholesterol clefts and cellular debri and variable amounts of fibrin and other plasma
proteins. Interspersed within the lipid material are lymphocytes and lipid-laden cells with the
appearance of “foamy cells”. These cells are histiocytes or smooth muscle cells (coming from
media) that have phagocyted the lipid material.

34. INFARCTUS MYOCARDII (Myocardial infarct)

An infarct is a localized area of ischemic necrosis in an organ or tissue resulting from

sudden obstruction of either its arterial supply or venous drainage. Acute myocardial infarcts
may take one of two forms 1. transmural infarction or 2. subendocardial infarction-with
occasional overlaps. Virtually all transmural infarcts involve the left ventricle (including the
interventricular septum). The irreversibly injured cells undergo typical ischemic coagulative
necrosis.
Histologically, the necrotic area is intensly eosinophilic (red) due to eosinophilia of the
sarcoplasm of necrotic cardiomyocytes; only shadows of the necrotic cardiomyocytes are
visible. The nuclei are not identified in necrotic cells. Neutrophilic exudation appears at the
margin of the infarct along the course of phagocytosis of the necrotic tissue. During the second
day the neutrophilic exudation becomes more marked, neutrophils infiltrate the necrotic tissue
(to perform phagocytosis), and the dead cardiomyocytes are more coagulated.
 HISTOPATHOLOGICAL FEATURES OF LUNG DISEASES

36. PNEUMONIA FIBRINOSA s. CRUPOSA - stadium HEPATISATIONIS

GRISEAE (Lobar pneumonia – gray hepatization)
Lobar pneumonia is a distinct entity meaning the inflamation of the entire pulmonary
lobe or of a large portion of a lobe. The inflammatory exudate is in the same stage throughout
the affected tissue.
Lobar pneumonia has been shown, in the classic literature, to progress through four stages: I
congestion; II red hepatization stage; III gray hepatization stage; IV resolution.
In the gray hepatization stage we can see diffuse alveolar consolidation. It means that there is
exudate within alveolar spaces. The exudate consists of neutrophils and macrophages in a fibrin
network. This exudate is widespread, with no alveoli to be spared.

37. BRONCHOPNEUMONIA FIBRINOSO-PURULENTA

(Fibrinous-purulent bronchopneumonia)
Synonym: Lobular pneumonia
Bronchopneumonia is lobular pneumonia which means that there is inflammatory infiltrate
within the given pulmonary lobulus which is drained by affected-inflammed bronchus and
bronchioles. Grossly, the involved region offers a mottled view of the affected part of the lung
with the alternation of the inflammed and uninflammed lobuli. Inflammed portion are gray-
yellow in colour and airless, usually 3 – 4 cm in diameter.
Histologically, some alveolar spaces are full of exudate. The exudate is composed of
granulocytes, macrophages and eosinophilic fibrin. Alveolar walls are relatively normal
Suppurative exduate is also present within bronchi and bronchioles which are sometimes seen
in the tissue section. On the same histological section, there are portions with normal alveoli,
without exudate.

38. BRONCHOPNEUMONIA CASEOSA TUBERCULOSA

(Tuberculous caseous bronchopneumonia)

Pulmonary tuberculosis is typically caused by Mycobacterium tuberculosis. Pulmonary

tuberculosis may manifest as caseous bronchopneumonia .
Massive caseous necrosis, destroying pulmonary tissue, with rare Langhans multinuclear giant
cells can be seen. The fields of caseous necrosis have basophilic, amorphous or fine-granular
appearance. In the peripheral zone with preserved tissue, many alveolar spaces contain fibrin
and lymphocytes, leukocytes and macrophages as a sign of non-specific pneumonia.
39. TBC MILIARIS PULMONIS (Miliary tuberculosis of the lung)

Miliary tuberculosis is named after the millet-seed-sized (1-2mm) tubercles. Miliary

tuberculosis predominantly affects pulmonary tissue, but it may be seen in many organs.
Miliary tuberculosis occurs after hematogenous dissemination from either primary pulmonary
tuberculosis or from isolated organ tuberculosis in the adults, such as genital or skeletal
tuberculosis.
Grossly, the miliary nodules are yellow when still active, and microscopically fill two to five
alveoli. Tubercles are composed of well-circumscribed epitheloid histiocytes with or without
Langhans giant cells, surrounded by lymphocytes. Central caseous necrosis may or may not be
present.

40. MEMBRANAE HYALINEAE PULMONUM (ARDS)

Synonyms: - Acute Respiratory Distress Syndrome (ARDS)
- Diffuse alveolar damage
Diffuse alveolar damage is the final common pathway for a variety of severe lung
injuries. In early stages, there are hyaline membranes as seen here, lining the alveoli. These
membranes are composed of fibrin and desquamated alveolar cells, and appear as pink,
eosinophilic strands lining alveolar spaces. Later in the first week after lung injury the hyaline
membranes resolve, and macrophage proliferation occurs. If the patient survives more than a
week, interstitial inflammation and fibrosis become increasingly prominent.

41. EMPHYSEMA PULMONUM (Pulmonary emphysema)

Emphysema is abnormal enlargement of air spaces. Macroscopically we can see bullae

if these air spaces are larger than 1 cm in diameter. Bullae are subpleural air-filled cystic air
spaces. They are found most frequently along the sharp margins of the lungs anteriorly and near
the apices.
Microscopically, the walls of bullae show fibrosis. Interalveolar septa are disrupted, and
alveolar spaces are coallesced. The remaining thin septa floate or protrude blindly into the large
emphysematous spaces.

42. SMALL CELL CARCINOMA (Oat cell)

Small cell carcinoma account for 15-20% of lung carcinomas. On gross examination
they appear as fleshy tumors forming nodules or infiltrating and destroying the wall of a major
bronchus.
The oat cell type consists of round or elongated poorly cohesive cells slightly larger than
lymphocytes. The tumor cells have dark dumped chromatin and little recognizable cytoplasm.
Nucleoli are absent or inconspicuous. Necrosis is usually present in larger tumors. The pattern
of tumor growth is diffuse but with some division into lobules by vessels and stroma, which
help to distinguish oat cell carcinoma from lymphoma.
HISTOPATHOLOGICAL FEATURES OF GASTROINTESTINAL DISEASES

43. ADENOMA PLEOMORPHE (TUMOR MIXTUS)

(Pleomorhic adenoma of the salivary gland = Mixed tumor of the salivary gland))

This is the most common tumor of the major salivary glands. Grossly, these tumors are
encapsulated, somewhat lobulated masses, ranging from 1 to 6 cm in diameter. The cut surface
is yellow-white and soft, but often there are blue-gray areas of increased consistency caused by
chondroid foci and other regions where the neoplasm is mucoid or gelatinous. However, within
an individual tumor there is considerable variability from one microscopic field to another.
Histologically, there is heterogeneity of epithelial and myoepithelial elements. The epithelial
cells form small strands and sheets or may form ducts, acini, irregular tubules, or microcysts.
These cells are cuboidal or columnar and are always uniform in size and shape. The
myoepitelial cells are smaller and darker and tend to be polygonal with an eccentric nucleus
and eosinophylic cytoplasm. Sometimes the myoepithelial cells are spindle-shaped. The stroma
is myxoid or hyalinized, sometimes with chondroid appearance.

44. GASTRITIS CHRONICA (Chronic gastritis)

Chronic gastritis is a chronic mucosal inflammatory process and encompasses a range

of lesions extending from nonatrophic (superficial) gastritis to atrophic gastritis. They make up
a morphologic continuum of increasingly intense inflammatory infiltration of the mucosa
accompanied by progressively more marked atrophy of the mucosal glands. Histologically, in
chronic nonatrophic (superficial) gastritis an inflammatory infiltrate of lymphocytes and plasma
cells is present within lamina propria with preservation of gastric glands. The inflammatory
inflitrate is most intensive in the upper third of the gastric mucosa, in the interfoveolar region.
The inflammatory infiltrate also extends into the lamina propria between the gastric glands.
Foveolitis and foveolar abscesses formation may be present. Foveolitis means the presence of
polymorphonuclear leukocytes within the fo veolar epithelium. Foveolar apscessus means the
presence of polymorphonuclear leukocytes within the foveolar lumen. Foci of intestinal
metaplasia is frequently seen, presenting as focal aglomeration of intestinal (small bowel and
colonic type) crypts.

45. ADENOCARCINOMA VENTRICULI (Gastric adenocarcinoma)

Carcinomas with glandular growth pattern microscopically are termed

adenocarcinomas. In the stomach, a favored location is the lesser curvature of the pyloro-
antrum.
Gastric cancers have been histologically divided into categories based on the
predominant cell type, and the presence of gland-like structures. Intestinal-type gastric
carcinoma, also thermed adenocarcinoma, consists of malignant glands. Malignant glands are
irregular in shape and size. They infiltrate the submucosa and muscle coat. Well-differentiated
adenocarcinomas form well-defined neoplastic gland-like structures lined by malignant
epithelial cells with oval hyperhromatic nuclei and visible nucleoli. These have cells with large
apical vacuoles (goblets) of mucus. The invasion of malignant cells of perivascular and
perineural spaces as well as blood and lymphatic vessels is sometimes evident. The conective
tissue stroma is desmoplastic (the malignant cells stimulate the formation of an abundant
collagenous stroma).
46. ULCUS VENTRICULI CHRONICUM (Gastric peptic ulcer)

Peptic ulcers are chronic, most often solitary lesions, predominantly found in the antrum
(the lesser curvature). They are usually small, less than 2 cm in diameter, round – to - oval,
sharply delineated. Peptic ulcers display relatively straight walls which are perpendicular to the
base of the ulcer. The base of all peptic ulcers is smooth and clean, owing to peptic digestion.
Histologically, four zones are encountered in the peptic ulcer:
1. a superficial thin layer of necrotic tissue with neutrophils,
2. the zone of coagulative (red in color) necrosis,
3. granulation tissue infiltrated with neutrophils, lymphocytes and plasma cells, and
4. the zone of fibrous tissue, underneath the granulation tissue.
In the mucosal margins there is a epithelial regeneration and chronic gastritis. Often the adjacent
mucosa contains intestinal crypts, a change described as `intestinal metaplasia`.

47. COLITIS ULCEROSA CHRONICA (Chronic ulcerative colitis)

This form of colitis is a recurrent acute and chronic ulceroinflammatory disorder of

mucosa of unknown etiology: The disease affects principally the rectum and left colon, but
sometimes the entire large bowel. Ulcerative colitis invariably begins in the rectum and spreads
proximaly in continuity.
Histologically, in the acute phase of disease there is the development of cryptitis and crypt-
abscessus. Cryptitis means the presence of neutrophils within the crypt epithelium. Crypt-
abscessus means the presence of neutrophils within the crypt lumen (where they reach from
crypt epithelium). Crypt-abscesses ultimately coalesce to form superficial ulcerations of the
mucosa. There is inflammatory infiltrate in the mucosal propria, consisting of neutrophils,
lymphocytes and plasma cells. At the margins of ulcers the remnants of the mucosa form
pseupolypoid structures, also exibiting cryptitis and crypt-abscessus.

48. ADENOCARCINOMA INTESTINI COLI (Adenocarcinoma of the colon)

About 70% of colorectal carcinoma are located in the rectum, rectosigmoid or sigmoid
colon. Carcinomas of the left side tend to grow in an annular encircling fashion with early
clinical symptoms of obstruction. On the right side, the lesions tend to grow as polypoid
fungating masses.
Histologically, the tumor consists of large irregular gland-like structures lined by
neoplastic columnar epithelial cells with oval hyperchromatic nuclei, visible nucleoli and
mitotic figures. These gland-like structures form back-to-back formation. Glandular lumens are
crowded by neoplastic cells. Malignant glands infiltrate the subumoca and muscle coat.
Transition zone between neoplastic glands of the adenocarcinoma and normal colonic
epithelium is quite visible. The connective tissue stroma is desmoplastic (the tumor cells
stimulate the formation of an abundant collagenous stroma).
49. CARCINOMA PANCREATIS (Carcinoma of the pancreas)

The term `carcinoma of the pancreas` is meant to imply the carcinoma arising from the
exocrine pancreas. Although duct cells make up only 4% of all pancreatic cells, the great
majority of all these cancers arise from the ductal epithelium – so called ductal
adenocarcinomas. Grossly, the gray-white, scirrous, homogenous tumor infiltrates and replaces
the usual yellow lobular architecture, with few foci of hemorrhage. Carcinoma of the head of
pancreas surrounds and compresses and less commonly directly invade the common bile duct,
or ampule of Vater, causing biliary obstruction and jaudnice (icterus). Histologically, most
carcinomas of the pancreas grow in more or less well-diferentiated gland-like patterns and are
thus adenocarcinomas. The gland-like formations are atypical, irregular, small and bizzare or
large. They are lined by malignant cuboidal-to-columnar epithelial cells. The tumors are
mucinous or non-mucin secreting. The connective tissue stroma is almost always desmoplastic.

HISTOPATHOLOGICAL FEATURES OF LIVER DISEASES

50. CHOLESTASIS

In liver, particularly with diseases caused by bile outflow obstruction (e.g. cancers of
the common bile duct and head of pancreas) bilirubin, in the form of yellow-green granules is
seen within hepatocytes, bile canaliculi (bile thrombi), Kupffer cells, bile ducts (bile cylinders)
and, if bile ducts rupture, bile lakes may be formed. Larger necrotic zone suffused with bile
pigment is called bile infarct.

51 . ADENOCARCINOMA VENTRICULI METASTATICUM IN HEPATE

(Metastatic gastric adenocarcinoma to the liver)

Gastric adenocarcinoma tends to give metastases to the liver.

Metastatic deposits are visible in liver tissue as irregular, gland-like structures lined by
neoplastic columnar epithelial cells with oval hyperchromatic nuclei and visible nucleoli. These
gland-like structures form back-to-back formations. Metastasis is oval in shape and well
demarcated from the surrounding liver tissue.

52. HEPATITIS VIROSA ACUTA (Acute viral hepatitis)

Viral hepatitis is an infection of the liver caused by any one of a small group of
hepatotropic viruses. All the hepatotropic viruses cause essentially the same clinical and
morphologic pattern of acute hepatitis, although that caused by HAV tends to be the mildest.
Fulminant hepatitis (presents with sub-massive to massive necrosis of hepatocytes), can lead to
hepatic failure, and is fortunately uncommon. During the early phase there is progressive loss
of liver substance (500 to 700 gm) and the liver becomes transformed into a red, limp organ
covered by a wrinkled, too large capsule. Histologically, the confluent, lytic necrosis may wipe
out entire lobules, or be less extreme. Most often, there is complete destruction of innumerable
contiguous lobules with lytic necrosis of hepatocytes, leaving only collapsed reticulin
framework and preserved portal tracts. There may be a scanty inflammatory infiltrate
(lymphocytes, macrophages and occasional neutrophils) within the portal tracts.
53. CIRRHOSIS HEPATIS (Hepatic cirrhosis)

Cirrhosis is a generic term for a hepatic disease of varied etiology (e.g. alcohol abuse,
chronic active hepatitis, drugs, iron overload…) having the following characteristics: 1. The
architecture of the total liver is disorganized by interconnecting fibrous scars formed in
response to hepatocyte injury and loss. 2. The fibrosis may take form of delicate bands, or may
constitute broad scars replacing multiple adjacent lobules. 3. Parenchymal nodules are created
by the regenerative activity. The nodules vary in size, from micronodules (less than 3mm in
diameter) to macronodules (3mm to 3cm in diameter), or combined. 4. The parenchymal
architecture is generally disorganized within micronodules.
A number of secondary changes follow. Abnormal vascular connections develop in the fibrous
scars between the portal, arterial and venous systems that by-pass the hepatic parenchima. A
mononuclear inflammatory infiltrate is usually located within the portal tracts and scars but is
of variable intensity.

54. CARCINOMA HEPATIS HEPATOCELLULARE

(Hepatocellular carcinoma of the liver)

About 80-90% of liver cell carcinomas arise in cirrhotic livers. There are several gross
patterns of growth and PH forms of liver cell carcinomas.
Histologically, well and moderately well-differentiated carcinomas are composed of
tumor cells that look like hepatocytes. There is the usual variation in cell and nuclear size,
prominent nucleoli and abnormal mitotic figures. The cytoplasm in some instances contains
inclusions of bile pigment. The differentiated cells are disposed either in a trabecular
(sinusoidal) or in acinar pattern. In sinusoidal pattern there are several layers of tumor cells,
separated by vascular channels, bearing some resemblance to sinusoids, embedded within a
connective tissue sheats. In the acinar pattern, the differentiated tumor cells are often disposed
about lumens. Sometimes these lumens contain plugs of bile.

HISTOPATHOLOGICAL FEATURES OF ENDOCRINE GLANDS AND BREAST

DISEASES

55. STRUMA COLLOIDES GLANDULAE THYREOIDEAE (Goiter)

In nodular goiter the gland is usually asymmetric, with nodules that very considerably
in size. Grossly the nodules may be colloidal or they may show degenerative features such as
hemorrhage, calcifications, fibrous scarring and cystic degeneration.
Histologically, the follicles may vary from small to large and the epithelium from flat
to tall. Nodules are predominantly composed of large dilated follicles full of inactive colloid.
Hemorrhage and an inflammatory infiltrate can be seen.
56. HASHIMOTO THYREOIDITIS
Grossly, the thyroid is three or four time larger than normal. The enlargement is usually
symmetrical, but in some instances it may have a nodular quality.
Histologically, the dominant feature is a massive infiltration of lymphocytes and
plasmocytes within the thyroid interstitium. Lymphoid follicles with pronounced germinal
centers are usually present. The follicular epithelium shows a widespread oncocytic change. At
higher power the oncocytic cells show nuclei of various size with a vesicular appearance.

57. PAPILLARY CARCINOMA (Papillary carcinoma of the thyroid gland)

Grossly, most cases are solid, firm, and clearly invasive; a complete capsule surrounds
fewer then 10%.
Microscopically, the diagnosis of papillary carcinoma depends on the presence of
papillary structures and/or characteristic nuclear appearance. The papillae are usually complex,
branching, with a central fibro-vascular core; they are lined with single or stratified cuboidal
cells. The nuclear features of papillary carcinoma are characteristic: ground-glass (optically
clear) nuclei, which often have a large size and nuclear pseudoinclusions. Mitoses are very
scanty or absent. Psammoma bodies are seen in approximately half of cases.

58. FOLLICULAR CARCINOMA (Follicular carcinoma of the thyroid gland)

Follicular carcinoma is more common in women. It typically presents as a solitary

thyroid nodule, light-tan or brown in colour, surrounded by a thick capsule.
The neoplastic proliferation has a microfollicular pattern, with considerable range in
follicular size and differentiation. Follicular structures range form well defined follicles
containing colloid to small abortive follicle formations. Hyperplastic changes in the form of
papillary or pseudopapillary structures may be seen. Less frequent there is increased mitotic
activity (usually focal), nuclear atypia and nuclear prominence. Carcinoma should be suspected
when these features are found but should be diagnosed only when invasion of the capsule is
seen.

59. PHEOCHROMOCYTOMA

Clinically tumor presents with hypertensive episodes as a result of catecholamine

release.
The tumor is composed of nests of tumor cells (“Cell balls”) separated by a thin fibro-
vascular stroma. The cells are uniform and polygonal with amphophilic, pale cytoplasm and
fairly well-defined cell borders. Nuclear pleomorphism is common with some bizarre cells.
There are no reliable histology criteria of malignancy.
60. FIBROCYSTIC CHANGES OF BREAST
Fibrocystic changes represent a proliferative response to increased estrogen stimulation.
Histologically, they present in several forms, which usually involve a combination of three
basic tissue responses: cyst formation, fibrosis and epithelial proliferation.
Obstructed ducts form cysts which are lined by flattened epithelium. Ductal epithelium
may occasionally transform into cuboidal eosinophilic cells resembling apocrine sweat glands.
This change is called apocrine metaplasia. In other cases, fibrosis predominates and the
epithelial proliferative changes are less apparent. The proliferation of epithelial cells results in
adenosis. Adenosis is sometimes accompanied by prominent fibrosis when it is called
sclerosing adenosis.
The form of fibrocystic change comprising adenosis, fibrosis and cysts is called simple,
to distinguish it from proliferative fibrocystic disease which is characterized by intraductal
epithelial proliferation.
Histologically, the normal lobular structure of the breast is lost, and the border between
intralobular and dense interlobular connective tissue is obscured. The ducts appear dilated.

61. FIBROADENOMA GLANDULAE MAMMAE (Fibroadenoma of the breast)

Fibroadenoma is a mixed epithelial-mesenchymal tumor.

Fibroadenomata are nodules, usually sharply circumscribed and freely movable from
surrounding breast substance and frequently occur in the upper outer quadrant of the breast (2
- 10 cm in size). On cut surface, they are composed of uniform, gray-white tissue punctuated
by elevated minute, yellow-to-pink softer areas (the glandular structures).
Microscopically, we found cellular, fibroblastic stroma enclosing glandular and cystic
spaces lined by epithelium. The epithelial cells are regular and cuboidal to polygonal in shape.
The basement membranes of these glands are intact and usually well defined (pericanalicular
fibroadenoma). In some tumors, or in some areas of the same fibroadenoma, glandular lumina
are collapsed, or compressed into slitlike, irregular clefts and the epithelial cells then appear as
narrow cords lying within the fibrous stroma (intracanalicular fibroadenoma).

62. CARCINOMA MAMMAE DUCTALE INVASIVUM

(Ductal invasive carcinoma of the breast)

Among breast carcinomas approximately 50% of cases arise in the upper outer quadrant.
The common type of breast cancer is infiltrating duct carcinoma. These growths occur as fairly
sharply delimited nodules of stony-hard consistency. Only rarely is there ulceration through the
skin.
Histologically, the tumor consists of anaplastic duct lining cells disposed in glands,
tubes, cords, solid cell nests and mixtures of all these. The tumor cells are small with
hyperchromatic regular nuclei. Theay are uniform in size and shape and display only a small
number of mitoses. The invasion of neoplastic cells of perivascular and perineural spaces, as
well as blood and lymphatic vessels is readily evident.
HISTOPATHOLOGICAL FEATURES OF KIDNEY AND URINARY TRACT
DISEASES

63. PYELONEPHRITIS PURULENTA (Purulent pyelonephritis)

The hallmarks of acute pyelonephritis are 1) patchy interstitial suppurative

inflammation and 2) tubular necrosis. The suppuration may occur as discrete focal abscesses
involving one or both kidneys, or as large, wedge-shaped areas of coalescent suppuration. The
neutrophilic infiltration is limited to the interstitial tissue. Later, the reaction has ruptured into
tubules and produced a characteristic abscess with the destruction of the engulfed tubules. Since
the tubular lumina present a ready pathway for the extension of the infection, large masses of
neutrophils frequently extend along the involved nephron into the collective tubules.
Characteristically, the glomeruli appear to be resistant to the infection.

64. GLOMERULONEPHRITIS ENDOCAPILLARIS S. ACUTA

(Acute poststreptococcal - proliferative glomerulonephritis)

The classical diagnostic picture is one of enlarged, hypercellular, relatively bloodless

glomeruli. The hypercellularity is caused by: 1) proliferation of mesangial cells and 2)
infiltration by leukocytes, both neutrophils and monocytes. The proliferation and leukocyte
infiltration is diffuse, i.e. involving all lobules of all glomeruli. There is also swelling of
endothelial cells, and the combination of proliferation, swelling, and leukocyte infiltration
obliterates the capillary lumina. Special stains can demonstrate small deposits of fibrin within
capillary lumina. There may be interstitial edema and inflammation, and the tubules often
contain red casts and may show evidence of degeneration.

65. NEPHROPATHIA DIABETICA – Diabetic nephropathy

Clinicaly: proteinuria rising to nephrotic sy.

Light microscopy: from mild mesangial widening to diffuse diabetic glomerulosclerosis;
nodular glomerulosclerosis is specific for diabetes (compacted matrix); formation of hyaline
(exudative) lesions: hyaline deposits in the Bowman’s capsule- “capsular drop” and “hyaline
caps”- over capilary loop (often could be found); hyaline deposition in intima and media of
both afferent and efferent arterioles; glomerular enlargement and GBM thickening; thickening
of the Bowman’s capsule and TBM (tubular atrophy), accompanied by interstitial fibrosis and
mononuclear infiltrates.
IF: interrupted linear deposits of immunoglobulines (IgG).
EM: GBM thickening, thick strands of essential matrix and their aggregation into nodules, early
hyaline deposits under endothelium.
66. CARCINOMA VILLOSUM VESICAE URINARIAE

(Papillary transitional cell (urothelial) carcinoma of the bladder)

It is a malignant tumor of bladder epithelial cells. Transitional cell carcinomas range from
noninvasive to invasive lesions, from flat to papillary, and from well differentiated (gradus I)
to highly anaplastic, aggressive cancers (gradus III). Papillary neoplasms have a complicated
fingerlike structures composed of a delicate connective tissue stalk, covered by malignant
transitional epithelium like cells that ranges from gradus I to gradus III. There is significant
increase in the number of layers of cells, i.e. more than seven layers, with loss of cell polarity.
Variability in cell size, shape, and chromasia is present. Mitoses may be numerous.

67. CARCINOMA LUCIDOCELLULARE RENIS (Renal cell carcinoma)

Synonym: HYPERNEPHROMA

The tumor affects the poles of the kidney, particularly the upper one. The margins are usually
sharply defined and confined within the renal capsule.
However, small satellite nodules are often found in surrounding substance. One of the striking
features of this tumour is its tendency to invade the renal vein and grow as a solid column of
cells within this vessel (permeation).
Histologically, the growth pattern varies from papillary to solid, trabecular (cordlike) or
tubular (resembling tubules). The most common tumour cell type is the clear cell, having a
rounded or polygonal shape and abundant clear cytoplasm; the latter contains glycogen and
lipids. Rarely, renal cell carcinoma consists of granular cells, which have a moderately
eosinophilic cytoplasm, or contain spindle-shaped cells resembling mesenchymal tumours.
Most tumours are well-differentiated (gradus I and II) but some (gradus IV) show
marked nuclear atypia with formation of bizarre nuclei and giant cells. The stroma is usually
scanty but highly vascularized.

68. WILMS TUMOR

Wilms tumor or nephroblastoma is a malignant tumor of infancy and childhood. The

tumor presents as an abdominal mass, which is usually one-sided except in 10% of cases, when
it is bilateral.
On gross examination, the tumor sometimes appears as a discrete mass but more often
it invades, permeates, and replaces the entire kidney. On cross-section, the tumor appears
grayish-white and has a solid fleshy or myxomatous and focally gritty structure. Histologically,
several tissue components appear intermixed at random. These include undifferentiated small
blue cells arranged into nests without any pattern (“blastema”) and surrounded by loose stroma,
small epithelial cells forming tubules and abortive glomeruli, and strands of connective tissue
that appear “sarcomatoid” as in leiomyosarcomas or fibrosarcomas. The tumor may contain
various heterologous elements such as cartilage, striated and smooth muscle, and fat tissue.
Areas of necrosis and hemorrhage are also common.
HISTOPATHOLOGICAL FEATURES OF MALE AND FEMALE GENITAL TRACT
DISEASES

69. EPIDIDIMYTIS PURULENTA SUBACUTA

(Subacute purulent epididymitis)

Epididymitis and possible subsequent orchitis are commonly related to infections in the
urinary tract (cystitis, urethritis, prostatitis). Two sexually-transmitted diseases, gonorrhea and
non-gonococcal urethritis (caused by Chlamydia trachomatis) are also important causes of
epididymitis.
The bacterial invasion causes a nonspecific acute inflammation characterized by tissue
infiltration of neutrophils, lymphocytes and macrophages. Although the infection in the early
stage is more or less limited to the interstitial connective tissue, it rapidly extends to involve the
tubules and may progress to frank abscess formation or diffuse suppurative inflammation of the
entire epididymis.
Any such nonspecific infection may become chronic.

70. SEMINOMA TESTIS (Seminoma of the testicles)

Seminomas are the common type of malignant germinal tumor (40%), with the peak in
the fourth decade. Three histologic variants of seminoma are described: typical (85%),
anaplastic (5 to 10%) and spermatocytic (4 to 6%). Grossly, the typical seminoma has a
homogenous, gray-white lobulated cut surface.
Microscopically, the typical seminoma presents sheets of uniform population of cells,
divided into poorly demarcated lobules by septa of fibrous tissue. These cells are large and
round and have a distinct cell membranes, clear cytoplasm and a large, central, hyperchromatic
nucleus with one or two prominent nucleoli. Mitoses are infrequent. The giant cells may be
present. Stroma my be scant or abundant. The septa are infiltrated with lymphocytes in 80%
that reflect an immune response and better prognosis.

71. HYPERPLASIA ADENOSTROMALIS PROSTATAE

(Benign Prostatic Hyperplasia)

Prostatic hyperplasia is an extremely common disorder in men over age 50. It is

characterized by the formation of large, fairly discrete nodules in the periurethral region of the
prostate. When sufficiently large, the nodules compress and narrow the urethral canal to cause
partial, or sometimes virtually complete, obstruction of the urethra. The nodules do not have
true capsule.
Microscopically, the prostatic glands are proliferated, enlarged and lined by the
hiperplastic, stratified epithelium. Prostatic stroma may be also hyperplastic. Usually, the
epithelial hyperplasia dominates and may take the form of aggregations of small, large or
cystically dilated glands.
72. GRAVIDITAS TUBARIA (Ectopic pregnancy in the Fallopian tube)

Ectopic pregnancy is the nonspecific term applied to implantation of the embryo in any
site other than normal uterine location. The most abnormal location is within the Fallopian tubes
(approximately 90%). In tubal pregnancy, the placenta is poorly attached to the wall of the tube.
More often, invasive placental tissue invades the wall, weakens the tubal wall and causes
tubal rupture and intraperitoneal hemorrhage. Horionic villi are present in the hemorrhagic
content of Fallopian tube. Placental tissue is poorly attached to the wall of the tube.

73. HYPERPLASIA ENDOMETRII SIMPLEX NON-ATYPICA

(Simple endometrial hyperplasia without atypia)

Endometrial hyperplasia is the common cause of abnormal bleeding.

Histologically, simple endometrial hyperplasia without atypia is characterized by the presence
of increased number of glands of various size, some of them being cystic. The epithelial lining
is multilayered cuboidal or tall columnar. There is no cytological or nuclear atypia. Mitoses are
scant. The stroma between glands is also hyperplastic.

74. ADENOCARCINOMA ENDOMETRII (Endometrial adenocarcinoma)

Histologically, most endometrial carcinomas are adenocarcinomas characterized by

more or less well-defined gland-like structures lined by malignant stratified columnar epithelial
cells. They have oval hyperchromatic nuclei, visible nucleoli and abnormal mitotic figures. The
connective tissue stroma is abundant.

75.CYSTADENOMA OVARII SEROSUM PAPILLARE

(Serous ovarian cystadenoma)

Common benign, often multilocular ovarian tumor, usually large, spherical, ranging
from 10 cm to 15 cm in diameter, but may be as large as 40 cm.
Histologically, serous ovarian cystadenoma is lined by tall, columnar, ciliated epithelial serous
secreting cells similar to the eputhelium of the Fallopian tube. The epithelium my line stromal
papillae which exhibit a broad fibrous core.

76. MOLA HYDATIDOSA (Hydatiform mole)

The true hydatidiform mole is a benign tropholoblastic tumor. Most patients are at the
fourth or fifth month of pregnancy with vaginal bleeding and with a uterus that is usually, but
not always, larger than expected for the duration of pregnancy. The uterine cavity is filled with
a delicate, friable mass of thin-walled, translucent, cystic, grape-like structures.
Microscopically, the mole shows hydropic swelling of chorionic villi, the absence or inadequate
development of vascularisation of villi and variable degrees of hyperplasia of the chorionic
epithelium. The central substance of the villi is a loose, myxomatous edematous stroma. Villi
are covered by a thin layer of chorionic epithelium, both cytotrophoblast and syncytial
trophoblast.
77. CHORIOCARCINOMA

Gestational choriocarcinoma is an epithelial malignancy of trophoblastic cells derived

from any form of previous normal or abnormal pregnancy. It is one of the most rapidly invasive
widely metastazing malignancy.
Histologoically, the tumor is composed of abnormal proliferation of both
cytotrophoblast and syncytiotrophoblast, without chorionic villi. The tumor invades the
uderlying endometrium, and blood vessels with subsequent hemorrahge and secondary
inflammatory reaction.

78. TERATOMA MATURUM (Mature teratoma)

The great majority of germ cell tumors are composed of cells representative of a single
germ layer. The teratoma, in contrast, is made up of a variety of parenchymal cell types which
represent more than one germ layer, usually all three germ cell layers. They arise from
totipotential cells, being principally encountered in the gonads. These totipotential cells
differentiate along various germ lines, producing tissues that can be identified as skin, muscle,
fat, gut and respiratory epithelium, thyroid gland and, indeed, any tissue of the body.

HISTOPATHOLOGICAL FEATURES OF HEMATOPOIETIC DISEASES

79. HYPERPLASIA FOLLICULARIS LYMPHONODI

(Follicular hyperplasia of the lymph node)

Lymph nodes respond to a wide variety of inflammatory stimuli by a cellular proliferation which
leads to node enlargement. The cell type which proliferates is dependent upon the antigenic stimulus,
which may elicit a predominantly B-cell response with germinal centre hyperplasia. Numerous enlarged
follicles with germinal centers are seen, and they may be present throughout the node, not restricted to
the outer cortex as in the normal state. The germinal centers are active, with a predominance of large
blast cells, and often contain numerous tingible body macrophages. There may be an expanded marginal
zone which may form the thick rim around the germinal centre.

80. HODGKIN LYMPHOMA

The term Hodgkin’s disease has been used for a type of malignant lymphoma in which Reed-
Sternberg tumor cells are present, surrounded by a “background” of reactive inflammatory cells of
various types, accompanied by fibrosis of variable degree. The predominant non-neoplastic cells are
small T-lymphocytes, with or without an accompanying population of benign-appearing histiocytes. The
lymph node architecture is partially or totally effaced, and the infiltrate may have a diffuse or nodular
pattern of growth with presence of eosinophils, plasma cells, and foci of fibrosis which may be scanty
or absent. Identification of typical Reed-Sternberg cells is necessary for the diagnosis of Hodgkin’s
disease. The classic Reed-Sternberg cell is a large cell with bilobate,”mirror image” nuclei and “owl’s
eye” nucleoli. Nucleoli are prominent, usually round and acidophilic. Diagnosis of nodular sclerosis
type of Hodgkin’s lymphoma is based on lacunar cells- Hodgkin’s cells surrounded by a clear space
(“lacuna”), and thick collagen bands which dissect the lymph node into nodules.
81. SMALL LYMPHOCYTE LYMPHOMA

This is a type of B cell low grade non-Hodgkin lymphoma.

Histologically, the lymph node architecture is totally obscured by diffuse monotonous sheets of mostly
small lymphocytes that lack any recognizable histologic pattern. The cells are small, round, and uniform,
resembling inactive, mature lymphocytes.

82. DIFFUSE LARGE B-CELL LYMPHOMA

Diffuse large B-cell lymphoma is intermediate grade non-Hodgkin lymphomas.

As the name implies, this lymphoma is characterized by a diffuse outgrowth of large B-cells which may
display centroblastic or immunoblastic cytology (here in tonsil).

83. BURKITT LYMPHOMA

Burkitt’s lymphoma is a high grade B-cell lymphoma associated with specific chromosomal
translocation involving the c-myc gene (here in intestine).
The disease affects children and adolescents, and involves extranodal sites such as jaw, gastrointestinal
tract and gonads.
The histological appearance is distinctive, with tightly packed, medium-sized lymphoid cells
interspersed with non-neoplastic phagocytic macrophages which impart a “starry-sky” appearance in
histological sections. There is a very high proliferation rate, with almost 100% of cells in cell cycle.

HISTOPATHOLOGICAL FEATURES OF SKIN LESIONS

84. NAEVUS NAEVOCELLULARIS (COMMON MELANOCYTIC NEVUS)

Benign tumor composed of melanocytes (nevus cells). Histologically, depending on the
location of nevus cells, nevocellular nevi are classified as junctional, if the cells are in the lower
parts of the epidermis, dermal, if the nevus cells are in the dermis, or compound, if the nevus
cells are both in the dermis and in the epidermis. The upper dermis contains nests and sheets of
nevus cells. In the lower epidermis and upper dermis, nevus cells commonly resemble epithelial
cells, being usually cuboidal or oval in shape. They have distinct homogenous cytoplasm and a
large, round or oval nucleus.
Frequently, they contain melanin pigment in the cytoplasm. Such cells are called type A
nevus cells. Nevus cells in the mid-dermis are smaller and may resemble lymphoid cells (type
B nevus cells). Cells in deep dermis are spindle-shaped and resemble Schwann cells (type C
nevus cells). They are, usually, present in long-standing dermal nevi. Larger, multinucleate cells
are also frequently found in the upper and middle dermis. With time, fat cells can accumulate
between nevus cells, sometimes in significant amount.

85. KERATOSIS SEBORRHOICA (SEBORRHEIC KERATOSIS)

Seborrheic keratosis (senile wart) is a benign epidermal tumor, much more common in
the elderly. Histologically, epidermal projections grow outwards, above the plane of the
adjacent epidermis. They have irregular surface with keratin tunnels extending deeply from the
surface inwards (keratotic plugs), that, on cross sectioning, appear as horn cysts.
 Tumor cells are similar to the basal cells of the epidermis, with various amount of
melanin pigment along basal layer or scattered throughout the lesion. There is a combination
of hyperkeratosis (thickened corneal layer), acanthosis (proliferation of the spinous layer) and
in some cases papillomatosis (upward projections of dermal papillae).

86. DERMATOFIBROMA
Dermatofibroma is a benign fibrous histiocytoma localized in the dermis.
Histologically, dermatofibroma consists of a nodular cellular proliferation involving dermis and
occasionally superficial subcutaneous tissue. The lateral margins are not sharply defined. The
overlying epidermis is hyperplastic, showing acanthosis often associated with basal layer
hyperpigmentation. The tumor consists of short, intersecting fascicles of spindle cells in
whorled (storiform) arrangement, with variable number of small blood vessels. Multinucleated
giant cells, inflammatory cells (lymphocytes), xanthomatous (foam) cells and
hemosiderophages may also be encountered. Tumor cells are often wrapped around collagen
bundles („collagen trapping“).

87. HAEMANGIOMA CUTIS

Benign neoplastic proliferation of blood vessels. There are several histological and
clinical variants. Capillary hemangiomas are composed of small blood vessels that conform to
the caliber of normal capillaries. Juvenile capillary hemangiomas are manifested soon after
birth. Histologically, in the initial phase, they are made up of closely packed endothelial cells
with some areas of small, thin-walled capillaries, separated by scant connective tissue stroma.
Later, vessels became dilated, lined with flattened endothelium. Growth pattern similar to
mature juvenile capillary hemangioma is seen in adults as cherry angioma.
Specific type of capillary hemangioma is pyogenic granuloma, named after commonly
(but not necessarily) present inflammatory component, caused by superficial trauma and
erosion of the skin overlying the hemangioma. Alternative denomination is lobular capillary
hemangioma, indicating its lobular growth pattern of capillaries separated by loose fibrous
stroma. Tumors composed of dilated, irregular, thin walled vascular spaces are sometimes
called cavernous hemangioma, but they probably represent malformations or may be found in
deeper parts of capillary hemangiomas or later during their evolution.

88. MELANOMA MALIGNUM (MALIGNANT MELANOMA)

Malignant melanoma (MM) is a malignant tumor of melanocytes. Histologically, MM
(with the exception of nodular type) have intraepidermal component showing lentiginous
(individual melanocytes along basal layer), nesting (irregular, discohesive aggregates of tumor
cells at the dermo-epidermal junction) and/or pagetoid (individual cells or small cell clusters
throughout the epidermis) growth pattern. In the dermis, malignant cells usually produce large
sheets or nests that can extend from papillary dermis to the subcutaneous fat tissue and
sometimes even deeper. There are two types of tumors cells: the epithelioid type and spindle-
shaped cell type. Epithelioid cells are larger than nevus cells, vary in size and shape, and contain
large nuclei with prominent nucleoli. Spindle cells are elongated, with hyperchromatic nuclei
and sometimes pronounced fibrous stroma. Mitotic figures, present in variable numbers, can be
found in all tumor parts, and atypical forms may be found as well. The amount of melanin
pigment and inflamm atory infiltrate vary (from absent to extensive).
89. CARCINOMA PLANOCELLULARE CUTIS (SQUAMOUS CELL CARCINOMA)
Squamous cell carcinoma may occur anywhere in the skin and on the mucous
membranes lined with squamous epithelium. On histological examination, the tumor consists
of irregular sheets and nests of epidermal cells that proliferate downward, into the dermis. The
cells are squamous cells showing variable degree of keratinization and nuclear atypia.
Keratinization can be diffuse or in the form of horn pearls. In the he dermis, usually
mononuclear, inflammatory infiltrate is common finding..

90. CARCINOMA BASOCELLULARE CUTIS (BASAL CELL CARCINOMA)

Basal cell carcinomas are seen on hair-bearing skin, especially on the face. The tumor
cells have oval or elongated, darkly stained nuclei and relatively scant cytoplasm, resembling
basal cells of the epidermis, but with larger nucleus/cytoplasm ratio. Usually, there is no
pronounced variation in cell size and shape. The peripheral cell layer shows a palisaded
arrangement, while stromal shrinking produce empty space that separate tumor nests from the
surrounding fibrous stroma. Most frequently found HP types of BCC are superficial, nodular
(including nodulo-cystic and adenoid), infiltrative (including morpheaphorm) and
micronodular, the last two being more aggressive, showing deeply invasive growth that make
them difficult to eradicate with one surgical procedure.

HISTOPATHOLOGICAL FEATURES OF BONE AND JOINT DISEASES AND SOFT

TISSUE TUMORS

91. SYNOVITIS CHRONICA (Chronic synovitis)

The characteristic changes are: 1) marked thickening of the synovial membrane,
forming edematous, villous projections that extend into the joint space; 2) shedding of lining
epithelium and 3) an intense infiltration of the synovia with macrophages, lymphocytes, and
plasma cells, sometimes with the formation of lymphoid follicles.

92. OSTEOMYELITIS CHRONICA (Chronic osteomyelitis)

The histologic changes depend entirely on the stage of the osteomyelitis and its duration.
Basically, two elements can be identified: suppuration and ischemic necrosis and fibrous and
bony repair. Inflammatory infiltrate consists predominantly of lymphocytes and plasma cells,
although foci of neutrophils may be seen. In areas of destruction of the bone tissue, remarkable
reactive osteoblastic activity is present.

93. CHONDROMA
This is a benign tumor composed of mature hyaline cartilage. Because such tumors most
often arise centrally within the interior of a bone, they are frequently called “enchondromas”.
Histologically, the tumor is composed of masses or islands of hyaline cartilage enclosed within
a vascularized fibrous stroma. Cartilage cells are irregularly dispersed throughout the matrix
and are set within clearly defined lacunar spaces. Often there are foci of calcification.
94. EWING`S SARCOMA
Histologically, the tumor is composed of sheets of quite uniform, small cells resembling
lymphocytes, but they are considerably large. The cells in occasional tumors are more
pleomorphic and have less regular nuclei, features that point to a poorer prognosis, but generally
mitotic figures are scant. There is remarkably little intercellular stroma, and much of the tumor
may be necrotic; often the best-preserved areas rim blood vessels. The tumor cells sometimes
ring a central clearing, creating “pseudorosettes”. (Significantly, this feature is typical of
neuroblastomas). Intracytoplasmic glycogen (PAS positivity) is a distinctive but not
pathognomonic feature.

95. TUMOR GIGANTOCELLULARIS (Giant cell tumor)

Giant cell tumors are characterized by a profusion of multinucleate giant cells scattered
throughout a stroma, which consists of mononuclear cells. Because the giant cells have some
similarity to osteoclasts, these neoplasms have also been inappropriately called
“osteoclastomas”.
Histologically, giant cell tumors are composed mainly of nondistinctive mononuclear
cells having round to oval to spindle-shaped nuclei remarkably uniform in size. Scattered within
this background are numerous giant cells having as many as 100 benign-appearing nuclei
resembling those in the mononuclear cells. There may be foci of necrosis, hemorrhage,
hemosiderin deposition, and osteoid formation.

96. OSTEOSARCOMA

The malignant tumor of mesenchymal cells characterized by the direct formation of osteoid
or bone by the tumor cells. Most tumors arise in the medullary cavity of the metaphyseal end
of the long bones of the extremities in decreased order of frequency: in the lower end of the
femur/upper end of the tibia and upper end of the humerus and upper end of the femur. The
neoplasms appear as gray-white masses that often contain areas of hemorrhage and cystic
softening.
Histologically, these tumors vary in the amount of the osteoid and/or cartilaginous matrix.
The vascular component is variable. The basic tumor cells are malignant osteoblasts which
surround the osteoid matrix; the malignant osteoblasts are also always present within the osteoid
matrix. These cells are pleomorphic with hyperchromatic muclei. Mitoses are readily seen.
Osteoclast-like giant cells may be present.

97. LIPOMA

The lipomas are extremely common benign tumors, found principally in the subcutaneous
tissues on the neck, face, hands and feet, but they also occur in deeper structures such as in
retroperitoneum, skeletal muscles, mediastinum. Lipomas are small (1 - 4cm in diameter),
poorly delineated and encapsulated.
On microscopy, the tumor is composed of mature lipocytes (polygonal cells with fat), ie. there
is no cellular or nuclear atypia. The cytoplasm of these cells looks empty because of the
extraction of the fat during tissue fixation. Between the lipocytes there is scant fibrous tissue
with small blood vessels (stroma).
98. LEIOMYOMA

The benign tumors of smooth muscle cells are found most often in the uterus and indeed
the leiomyomas are the most frequent tumors in women. They are sharply delineated,
unencapsulated, usually round, firm, gray-white masses. They are found within the
myometrium of the corpus. There are three localisations: intramural (embedded within the
myometrium), submucous (in immediate proximity to the endometrium) and subserosal
(beneath the covering serosa of the uterine corpus). If they are large, the areas of hemorrhage
and necrosis may be found.
Histologically, the tumor is composed of long intersecting bundles of well-differentiated
smooth muscle cells which are uniform in size and shape, with uniform oval nuclei. Mitotic
figures are absent.

99. RHABDOMYOSARCOMA

Rhabdomyosarcoma is a malignant tumor of striated muscle origin. It is derived from

primitive mesenchyme that retained its capacity for skeletal muscle differentiation.
Histologicali rhabdomyosarcoma is divided into 5 major histologic categories: embryonal,
alveolar, botryoid embryonal, spindle cell embryonal, and anaplasic (previously called
pleomorphic).
On histologic examination, rhabdomiosarcomas have high cytologic variability, which
represents several stages of skeletal muscle morphogenesis. They may range from highly
differentiated neoplasms containing rhabdomyoblasts with large amounts of eosinophilic
cytoplasm and cross striations similar to that of poorly differentiated tumor cells. Sometimes
these tumors have the appearance of club-shaped tumor cells arranged in clumps and outlined
by fibrous septa. In the center, the clusters are arranged loosely, and therefore, they appear in
an alveolar pattern (typical for alveolar subtype).
Anaplastic rhabdomyosarcoma is defined by large, lobate hyperchromatic nuclei and
multipolar mitotic figures.

100. LEIOMYOSARCOMA

The malignant tumor derived of the smooth muscle cells. Grossly, leiomyosarcoma has
the typical soft fish-flesh appearance, often punctuated by areas of hemorrhage, necrosis and
cystic degeneration. The most frequent localization are deep tissues, ie. retroperitoneum.
Microscopically, the well differentiated tumor is composed of long intersecting fascicles of
tumor cells. The cells are elongated, spindle-shaped, reminiscent of smooth muscle cells.
The cytoplasm is eosinophilic. In well differentiated tumors longitudinal striation within
cytoplasm can be seen. The nuclei are elongated with blunt edges - “cigar-shaped”. In the well
differentiated tumors, mitoses are rare. In the less differentiated tumors, the cells and nuclei are
more pleomorphic, loosing spindled shape, and mitoses are more frequent. Less differetiated
tumors contain frequently necrosis and hemorrhage. The connective tissue stroma is scant.
HISTOPATHOLOGICAL FEATURES OF CNS DISEASES

101. HAEMORRHAGIA CEREBRI HYPERTENSIVA

(Hypertensive cerebral hemorrhage)

Hemorrhage into brain substance is caused by hypertensive cerebral vascular disease

(80%). Other associated conditions include trauma, rupture of aneurysms, angiomas, blood
dyscrasias and bleeding into tumor. The surrounding tissue is ringed with multiple smaller
perivascular hemorrhages. The architecture of brain is destroyed and replaced by blood.
Histologically, the lesion is characterized by a central core of clotted blood surrounded by a rim
of brain tissue showing anoxic neuronal and glial changes as well as edema. Pigment-laden and
lipid-laden macrophages appear, and proliferation of reactive astrocytes is seen at the periphery.
The macrophages become activated, they phagocyte red cells and become filled with
hemosiderin. The microglia becomes very active, it surrounds focus of hemorrhage. The
microglia (granular cells) have golden-brown granules of hemosiderin in the cytoplasm

102. INFARCTUS CEREBRI (Cerebral infarct)

Infarction of the brain (encephalomalacia) is the consequence of the deprivation of blood

supply to a localized area.
In early stages (12 – 24 hrs after the insult), neurons display eosinophilia of the
cytoplasm and later nuclear pyknosis and karyorhexis. Similar changes are seen in atrocytes
and oligodendroglia.
The slides show the later change (24 hrs – 2 weeks): the infarcted area manifests as a
focus of destroyed brain tissue, namely, brain tissue is necrotic and unrecognizable. There is
edema in the surrounded brain tissue. Within necrotic area there is influx of polymorphonuclear
leukocytes (up to 48 hrs) and macrophages which are microglia. After phagocytosis, microglia
is seen as round eosinophilic cells with small nuclei and granular, foam, cytoplasm. Pale and
granular cytoplasm of microglia is due to phagocyted lipids from necrotic brain tissue.
.

103. LEPTOMENINGITIS PURULENTA (Purulent leptomeningitis)

Leptomeningitis is an acute inflammation limited to the leptomeninges and

subarachnoid space. Etiological agents are pneumococci and meningococci in adults,
haemophylus influenze in infants, and Escherischia coli, pseudomonas and proteus in
newborns. In pneumococcal leptomeningitis the exudate is more often located over the
cerebral convexities near the longitudinal sinus.
On microscopic examination, there is a typical neutrophilic exudation in the
subarachnoid space with varying amounts of fibrin. In fulminant infections the inflammatory
cell infiltrates the walls of the leptomeningeal veins, producing vasculitis.
104. LEPTOMENINGITIS TUBERCULOSA (Tuberculous leptomeningitis)

Tuberculosis may occur in the nervous system as an leptomeningitis or an

intraparenchymal tuberculoma. Tuberculous leptomeningitis occurs in children and adults
through hematogenous spread to the CNS or by erosion of a superficial parenchymal granuloma
into the subarachnoid space. In the most fatal cases a thick exudate is present at the base of the
brain.
Microscopic features include acute and chronic inflammatory cells, granulomas with
and without caseation necrosis and infrequent giant cells. Vasculitis and small parenchymal
infarcts are common occurences.
In some cases, meningeal tissue is affected by large amounts of caseous necrosis, only
(without recognizable epithelioid or giant cells).

105. ENCEPHALITIS VIROSA (Viral encephalitis)

Grossly, in acute cases, the brain and spinal cord are congested and edematous and small
hemorrhages may be seen.
Microscopically, in the gray matter mononuclear cells form perivascular cuffs around
parenchymal blood vessels. The most important feature are the changes in the nerve cells:
cytoplasmic swelling, chromatolysis and nuclear disappearance. These cells are surrounded by
microglial cells (neuronophagocytosis).

106. MENINGIOMA
A primary tumor of the meninges, usually benign (gradus I), arise from arachnoid cells
within the arachnoid villi, hence the localisation of these neoplasms more or less parallels the
sites where villi are most numerous. The most frequent site of intracranial menigniomas is the
parasagital region followed by the lateral cerebral convexity and the falx cerebri. They can
occur at any age. Grossly, the tumors tend to be irregular-to-round, lobulated white-gray
masses, well circumscribed. The cut surface of some tumors is gritty.
On microscopic examination, meningiomas can be subclassified into several forms. The
meningotheliomatous (syncytial) lesions are composed of epithelial-like cells with abundant
cytoplasm, indistinct cytoplasmic borders and well-defined oval nuclei. Whorls of tumor cells
are a conspicious feature often enclosing psammoma bodies. They are concentrically laminated
structures formed by the deposition of calcium salts in degenerated tumor cells.

107. GLIOBLASTOMA MULTIFORME

Glioblastoma multiforme is the most malignant type of all the gliomas (gradus IV).
Grossly, they often appear to be well circumscribed, although they always infiltrate the
surrounding brain. Some regions may be white and firm, the others yellow and soft. Cystic
softenings, foci of necrosis and hemorrhages are more typical for glioblastomas than any other
brain tumor.
Microscopically, the tumors are generally anaplastic, with hypercellularity and a
striking cellular pleomorphism ranging from small, elongated, irregular undifferentiated cells
to giant, bizarre forms. Necrosis, abnormal mitoses and proliferation of blood vessels are
usually prominent. Mostly, some areas contain recognisable astrocytes.