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IJPP-277; No. of Pages 13 ARTICLE IN PRESS

International Journal of Paleopathology xxx (2017) xxx–xxx

Contents lists available at ScienceDirect

International Journal of Paleopathology

journal homepage: www.elsevier.com/locate/ijpp

Histology of ancient soft tissue tumors: A review

Gino Fornaciari
Division of Paleopathology, Department of Translational Research on New Technologies in Medicine and Surgery, University of Pisa, Medical School, Via
Roma, 57, 56126 Pisa, Italy

a r t i c l e i n f o a b s t r a c t

Article history: Ancient neoplasms diagnosed in the soft tissues of mummies are limited to 18 cases so far, with only 5
Received 23 February 2017 malignant tumors. The apparent paucity of neoplasms in ancient populations is sometimes attributed to
Received in revised form 25 February 2017 shorter life spans and fewer oncogenic substances in the environment. However, this paucity may also be a
Accepted 28 February 2017
result of the scarcity of autopsies of mummies, together with technical difficulties in detecting neoplastic
Available online xxx
lesions in mummified tissues. An exception, and example of the benefits of thorough systematic analysis,
is the small sample of 10 Renaissance mummies from Naples (15th–16th centuries), in which 3 cases of
Keywords:
cancer were found. In order to increase detection of soft tissue tumors, it is imperative that mummies
Ancient neoplasm
Cancer
undergo systematic autopsies and histological examinations performed by skilled paleopathologists. This
Histopathology review of the known ancient soft tissue neoplasms demonstrates the state of histology of malignant
Ancient DNA and benign soft tissue neoplasms in mummies, and the potential for further study. The limitations of
Paleopathology paleopathological diagnosis will be discussed and an argument will be made for the use of autopsies and
histological analysis on mummified human remains.
© 2017 Published by Elsevier Inc.

Contents

1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
2. Malignant tumors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
2.1. Colon . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
2.1.1. Rectal adenocarcinoma in a Roman Period Egyptian mummy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
2.1.2. Colorectal adenocarcinoma from Naples (15th century) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
2.1.3. Colon adenocarcinoma from Naples (16th century) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
2.2. Skin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
2.2.1. Basal cell carcinoma from Naples (16th century) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
2.3. Skeletal muscle . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
2.3.1. Rhabdomyosarcoma in a pre-Columbian mummy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
3. Benign Tumors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
3.1. Skin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
3.1.1. Solar keratosis with squamous papilloma from Egypt . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
3.1.2. 3.1.2. Verruca vulgaris from Egypt . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
3.1.3. Verruca vulgaris in an Inca mummy from Chile . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
3.1.4. Cutaneous angiokeratoma in an Inca mummy from Chile . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
3.1.5. Condyloma acuminatum from Naples (16th century) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
3.1.6. Histiocytoma from Egypt . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
3.2. Breast . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
3.2.1. Mammary fibroadenoma from Late Period Egypt . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
3.3. Mammary fibroadenoma from Naples (16th century) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
3.4. Ovary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
3.4.1. Ovarian cystadenoma from Egypt . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00

E-mail address: gino.fornaciari@med.unipi.it

http://dx.doi.org/10.1016/j.ijpp.2017.02.007
1879-9817/© 2017 Published by Elsevier Inc.

Please cite this article in press as: Fornaciari, G., Histology of ancient soft tissue tumors: A review. Int. J. Paleopathol. (2017),
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2 G. Fornaciari / International Journal of Paleopathology xxx (2017) xxx–xxx

3.5. Ovarian cystadenoma from central Italy (19th century) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00

3.6. Urinary bladder . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
3.6.1. Vesical papilloma from Roman Period Egypt . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
3.7. Nerve sheath . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
3.7.1. Neurilemmoma from Late Period Egypt . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
3.8. Adipose tissue . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
3.8.1. Lipoma from pre-Columbian Chile . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
4. Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
Funding . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00

1. Introduction 2.1.2. Colorectal adenocarcinoma from Naples (15th century)

The anthropogenic mummy of Ferrante I of Aragon
Although cancer currentlyrepresents the second leading cause (1424–1494), King of Naples, revealed a hollow fibrous struc-
of death in advanced countries (Torre et al., 2015), it has been said ture in the pelvis, identified as the rectum at autopsy. After
that the prevalence of cancer may have been lower in the past rehydration, the specimen reached a size of 14 × 6 × 1 cm (Fig. 2a)
(David and Zimmerman, 2010). The number of neoplastic lesions and on cross-section it appeared dark brown, with many small
documented so far in the paleopathological literature, distributed roundish grey-white areas 0.5–3.0 mm in diameter (Fig. 2b). His-
over a long time span and in different countries, includes about two tology revealed epithelial tumor cells, disposed in cords, solid nests
hundred cases in the skeletal apparatus (Strouhal, 1994; Capasso, and glands (Fig. 3a, b), disseminated in a fibrous stroma containing
2005; Hunt et al., in this issue). However, there are only eigh- striated muscular fibers (Fig. 4c). The cells were crowded and
teen cases of soft tissue tumors in the literature, all discovered tall, with abundant cytoplasm and pseudo-stratified pleomorphic
by paleopathologists (Fornaciari and Giuffra, 2012) using different hyperchromatic nuclei (Fig. 4a). Bizarre nuclei, with indentations
methods of rehydration (Ruffer, 1910; Sandison, 1955) and stain- and irregular clumps of chromatin appeared in electron microscopy
ing for light microscopy (Allison and Gerszten, 1982; Reyman and (Fig. 4b). The mucus was scarce and limited to pseudo-glandular
Dowd, 1980) or electron microscopy (Riddle, 1980). formations, as shown by the specific staining with Alcian-blue and
The main reasons for the rarity of soft tissue tumors in pale- PAS (Fig. 4d). These results pointed out a moderately differentiated
opathology, especially malignancies, are apparently the short life mucinous adenocarcinoma infiltrating the muscular-fibrous layers
span of past populations, the scarcity of mummified remains avail- of the small pelvis. A strong intracytoplasmic immunoreactivity
able in comparison with skeletal remains, and technical difficulties of the neoplastic cells for pancytokeratin was shown (Fig. 4e)
in the detection of neoplastic lesions in mummified tissues. This and a positive staining, showing actively proliferating cells, was
review of the known ancient soft tissue neoplasms demonstrates observed for Proliferating Cell Nuclear Antigen (PCNA) (Fig. 4f),
the state of histology of malignant and benign soft tissue neoplasms whereas Prostate-specific Antigen (PSA) and Carcinoembryonic
in mummies, and the potential for further study. The limitations Antigen (CEA) gave negative results. The histological, histochemi-
of paleopathological diagnosis will be discussed and an argument cal and immunohistochemical results clearly indicate a mucinous
will be made for the use of autopsies and histological analysis on adenocarcinoma of the digestive tract, most probably of the
mummified human remains. colorectum (Fornaciari, 1993).
DNA hybridization probe and sequencing analysis of K-RAS
exons 1–2 demonstrated the presence of the codon 12 GGT > GAT
2. Malignant tumors
transition (Marchetti et al., 1996; Ottini et al., 2011). This muta-
tion represents the most frequent mutation of the K-RAS gene in
2.1. Colon
sporadic colorectal cancer and is associated with exposure to chem-
ical carcinogens, probably present in the diet (Saffhill et al., 1985;
2.1.1. Rectal adenocarcinoma in a Roman Period Egyptian
Kuhnle and Bingham, 2007).
mummy
An increased intake of red meat is known to induce a signifi-
An abnormal tissue mass found in the rectum of an adult male
cant (3-fold) increase in fecal N-nitroso compound (NOC) levels,
mummy (West Cemetery #5, Body C) from the Dakhleh Oasis,
with a range of exposure evident in the feces similar to that from
Egypt, and dating back to the Roman Period, was examined his-
tobacco-specific NOC in cigarette smokers (Fornaciari et al., 1999).
tologically. The rectal wall was well-preserved, with a polypoid
A paleonutritional study with Carbon (13 C) and Nitrogen (15 N) sta-
mass protruding into the lumen and showing a relatively well-
ble isotopes revealed a massive intake of animal proteins caused
preserved hyperplastic colonic mucosa in a tubular pattern (Fig. 1a).
by a large consumption of meat by King Ferrante (Fornaciari, 2008),
The nuclei were not preserved, but the central portion of the lesion
and histology revealed severe atherosclerosis of the carotids (Gaeta
showed a deep invasion of the epithelium into the underlying
et al., 2013). In conclusion, the alimentary “environment” of the
muscularis (Fig. 1b, arrow). Although the cellular detail was not
Neapolitan court of the 15th century, with its abundance of natu-
well-preserved, the cells were shown to be periodic acid Schiff
ral endogenous alkylating agents, well explains the K-RAS mutation
(PAS)-positive and the reticulin stain showed an epithelial pattern,
that caused the tumor that killed the Aragonese king over five cen-
with clusters of cells surrounded by reticular fibers. Small clusters
turies ago.
of similar PAS-positive material were observed deep within the
muscularis, revealing a deep invasion through the wall (Zimmerman
and Aufderheide, 2010). The histological picture clearly demon- 2.1.3. Colon adenocarcinoma from Naples (16th century)
strated degenerated epithelial cells with prevalent non-invasive, Autopsy of the natural mummy of Luigi Carafa, Prince of
adenomatous structure, but some sections showed clear invasion Stigliano (1511–1576) (Fornaciari, 2006), showed “a hollow organ
and infiltration into the submucosa of an atypical glandular compo- with material” of about 8 × 3 cm, identifiable as a portion of a bowel
nent. This lesion is consistent with an infiltrating adenocarcinoma loop with feces. Histology revealed a tract of colon wall with very
occurring in a benign villous adenoma. well-preserved mucosa, submucosa, muscularis propria and vis-

Please cite this article in press as: Fornaciari, G., Histology of ancient soft tissue tumors: A review. Int. J. Paleopathol. (2017),
http://dx.doi.org/10.1016/j.ijpp.2017.02.007
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G. Fornaciari / International Journal of Paleopathology xxx (2017) xxx–xxx 3

Fig. 1. a: Transition of rectal mucosa into villous adenoma (Hematoxylin Eosin, 40X); b: central portion of the adenoma shows malignant transformation, with deep invasion
of the epithelium into the underlying muscularis (arrow) (PAS, 40 X) (courtesy of M. Zimmerman).

Fig. 2. a, b: Section of the hollow structure of small pelvis at stereomicroscope after

rehydration: tumor massively infiltrating the internal, dark brown tissues of the
pelvis with many roundish yellow-white areas 0.5–3.0 mm in diameter (8X and
16X).

Fig. 3. a, b: Pseudo-glandular lumina and solid cords of tumor infiltrating fibrous

ceral peritoneum (Fig. 5a). The mucosa showed many pedunculated
villous projections, with narrow or wide base, long fronds of pap-
illary epithelium, and strong positivity of immunohistochemistry
®
for keratins (Anti-Pan Keratin Ventana ) springing directly from
the mucosal surface (Figs. 5a, b; 6a ). Upon further magnification,
dysplastic epithelial cells with an increased nuclear-to-cytoplasmic
ratio, hyperchromatic nuclei and nuclear pseudo-stratification, and
atypical mucinous cells were apparent (Fig. 6b). This also revealed
a strong positivity of immunohistochemistry against the altered
®
protein p53 (anti-p53 [BP53-11] Ventana ), present in many ade-
nocarcinomas (Bruner et al., 1993). In general, cribriform glands
interfaced directly with the lamina propria of the basement mem-
brane with no evident invasion. However, in some points, clear
stroma (Hematoxylin Eosin, 40X and 100X).
invasion of the stalk of a polyp (Fig. 6b, arrow) or of submucosa
(Fig. 6a, arrow) was evident. The histological picture is that of a
well differentiated adenocarcinoma of the large bowel at stage T1,
developed on a colonic villous adenoma (Rosai, 1996).
It is quite probable that, in the last months of life, the prince
suffered from intestinal colic, cured by the court doctors. The excel-
lent histological preservation of the cancer cells could be partly
explained by the use of alchemic, toxic drugs with antimicrobial
activity used in the Baroque medicine of the 16th century; particu-

Please cite this article in press as: Fornaciari, G., Histology of ancient soft tissue tumors: A review. Int. J. Paleopathol. (2017),
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Fig. 4. a: Pseudo-glandular lumen with tall cells and abundant cytoplasm (Hematoxylin Eosin, 800X); b: Irregular neoplastic nuclei with indentations and irregular clumps of
chromatin (EM, 6,000X); c: Neoplastic cells infiltrating muscular fibers (Van Gieson, 400X); d: Positivity for mucus stain of neoplastic glands (Alcian blue, 400X); e: Intense
®
positivity of neoplastic glands for Anti-Pan Keratin Sorin (immunofluorescence, 100X); f: Nuclear PCNA positivity of neoplastic cells (400X).

larly by the Paracelsus followers, to cure the colic pains (Paracelsus,
1573).
A paleonutritional study with stable isotopes revealed a large
consumption of meat and minor consumption of marine fish by
the prince (Fornaciari, 2008). The study of other immunohisto-
chemical markers as well as of the molecular (aDNA) picture of this
extraordinarily well-preserved malignant tumor, that is unique in
the paleopathological literature, is in progress.
2.2. Skin
2.2.1. Basal cell carcinoma from Naples (16th century)
The natural mummy of Ferdinando Orsini, Duke of Gravina in
Apulia (southern Italy), who died in 1549 at 50–55 years of age,
showed a face completely covered by a veil and two small patches
of cloth at the root of the nose and on the right orbit (Fig. 7a). After
removal of the veil and the patches, surely a medical dressing, an
extensive and destructive lesion of the right orbit and the root of
the nose was apparent (Fig. 7b). At macroscopic examination, the
lesion revealed complete destruction of the right nasal bone and
root of the left nasal bone, and destruction of the medial wall of the
right orbit with extensive erosion of the glabellar region and the
upper third of the vomer (Fig. 7c).
The histology of eroded fragments of the vomer and left nasal
bone showed large lacunae with clear borders, surrounded by
other smaller round lacunae, destroying the normal lamellar bone,
sometimes containing clusters of partially necrotic cells with solid
epithelial-like aspects (Fig. 8a, b), well visible especially inside one
of the largest lacunae (Fig. 8c). The border between the bone and the
underlying tissue in the lacunae is clear and sharp and the brownish
epithelial-like mass reveals a darker margin (similar to a palisade),
and it is separated from the bone by clefting artifacts (Fig. 9a, b,
arrows). The epithelial origin of the cells of the osteolytic lesion
was confirmed by strong positivity for pancytokeratin.
The lesion of the facial skull of Ferdinando Orsini is macroscop-
ically and microscopically suggestive of a diagnosis of destructive
basal cell carcinoma in an advanced stage of evolution (Fornaciari
et al., 1989; Gaeta et al., 2015). This tumor, which presents strong
local aggressiveness and causes skin ulceration and bone destruc-
tion (hence the Latin name of ‘ulcus rodens’ or erosive ulcer), is
currently one of the most common malignant skin neoplasms
caused by exposure to sunlight (Crowson, 2006).
2.3. Skeletal muscle
2.3.1. Rhabdomyosarcoma in a pre-Columbian mummy
A male child mummy, 12–18 months old, found in northern
Chile and belonging to the Cabaza culture, dating from 300 to
600 CE., presented a large cheek tumor of 5.5 × 5.5 × 2 cm. The
lesion, in the form of a hard swelling localized on the mummy’s
right cheek below the eye, forced that eye to close, but did not
involve the bones of the right orbit. Histology showed pleomor-
phic, disintegrated cells surrounded by a delicate, fibrous stroma
(Fig. 10

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Table 1
Malignant soft tissue tumors in mummies.

No. Tumor Provenance Dating Age in years/Sex References

1 Rectum adenocarcinoma Egypt Roman Period adult/M Zimmerman and Aufderheide (2010)
2 Colorectal adenocarcinoma Naples 1494 70/M Fornaciari (1993), Marchetti et al.
(1996), Fornaciari et al. (1999), Ottini
et al. (2011)
3 Colon adenocarcinoma Naples 1576 65/M in this issue
4 Basal cell carcinoma Italy 1549 50–55/M Fornaciari et al. (1989), Gaeta et al.
(2015)
5 Rhabdomyosarcoma Chile 300–600 CE 1–2/M Gerszten and Allison (1991)

Fig. 5. a: Trait of colon wall with very well-preserved mucosa with villous pro-
jections, submucosa, muscularis propria and visceral peritoneum (Anti-Pan Keratin
®
Ventana , 20X); b: Pedunculated villous projections, with long fronds of papillary
epithelium and strong positivity at immunohistochemistry for keratins (Anti-Pan
®
Keratin Ventana , 50X).

a). Most of the cells revealed a shrunken cytoplasm; and in some

instances, nuclear material with a marked nuclear pleomorphism
could be observed (Fig. 10b) (Gerszten and Allison, 1991; Gerszten
et al., 2012). This histological picture is consistent with an alve-
olar rhabdomyosarcoma; a tumor occurring chiefly in sub-adults
under the age of 20 and also in very young children, as in this case
(Gerszten and Allison, 1991). More than 55% of rhabdomyosarcoma
cases have a primary location in the head and neck (Weichert et al.,
1976; Radzikowska et al., 2015) (Table 1).
3. Benign Tumors
3.1. Skin
3.1.1. Solar keratosis with squamous papilloma from Egypt
Histology of the hand skin of an adult female Egyptian mummy,
probably from the Late Period, showed a small ‘filiform’ squa-
mous papilloma, marked hyperkeratosis, and a rather thinned-out
epidermis (Fig. 11a). These changes suggest that the skin of this
individual was abnormal, with changes resembling those associ-
ated with solar keratosis (Fig. 11b) (Sandison, 1967).
3.1.2. 3.1.2. Verruca vulgaris from Egypt
A protruding lesion 0.7 cm in diameter was observed on the
neck of an Egyptian mummy from the Marro Collection in Turin,
Italy (Cat. No. 61). The lesion was a raised, brown, roundish mass.
Histology showed thickened epidermis with hyperkeratosis, parak-
eratosis, mild acanthosis, and some vascular spaces (Fig. 12). The
®
Fig. 6. a: Evident invasion of submucosa (arrows) (Anti-Pan Keratin Ventana ,
40X); b: Dysplastic epithelial cells with hypercromatic nuclei, nuclear pseudostrat-
ification, atypical mucinous cells and clear invasion of the stalk of a polyp (arrow)
®
(Anti-Pan Keratin Ventana , 160X).
cells revealed slight positivity to anti-keratin antibodies. The his-
tological picture is suggestive of verruca vulgaris (Fulcheri, 1987).
3.1.3. Verruca vulgaris in an Inca mummy from Chile
A frozen Inca mummy was found at a high altitude in the Andes,
on Cerro El Plomo, Chile. This 8–9 year old child, also known as
‘Prince of El Plomo’, was the victim of a human sacrifice (Horne,
1996). Two small lesions were observed at the base of the thumb
and index fingers of the left hand. These two rounded 2 mm neofor-
mations, examined with transmission electron microscopy (TEM),
revealed the presence of viral-like, round structures, identified as
human papilloma virus (HPV) (Fig. 13), allowing a diagnosis of ver-
ruca vulgaris (Horne and Kawasaki, 1984; Horne, 1996).
3.1.4. Cutaneous angiokeratoma in an Inca mummy from Chile
Eight ulcerated lesions affected the legs of the aforementioned
frozen Inca mummy. The lesions ranged from 0.5 to 1 cm in diam-
eter, had well defined borders, and were covered by fibrinous
exudate. Histology revealed numerous dilated vascular channels in
the superficial dermis, filled with homogeneous eosinophilic mate-
rial which may have been hemolyzed blood. These vessels appeared
to be capillaries and many were located immediately adjacent to

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Fig. 7. a: The face of Ferdinando Orsini covered by a veil and with two patches of cloth at the nose root and on the right orbit; b: Large, destructive lesion of the right orbit
and root of the nose; c: Complete destruction of the right nasal bone and the root of the left (nasal bone) and destruction of the medial wall of the right orbit with extensive
erosion of the glabella and the upper third of vomer.

the overlying epidermis, which sometimes appeared to encircle
the vessels. Larger dilated capillaries were also present in the sub-
cutaneous fat. The epidermis was thickened and hyperkeratotic,
with a papillary configuration where the capillaries are most abun-
dant (Fig. 16). In this area the lesion was ulcerated, with an acute
inflammatory exudate characterized by fibrin and an infiltrate of
polymorphonuclear leukocytes and other types of white blood
cells. The histologic features are consistent with an angiokeratoma,
probably angiokeratoma circumscriptum, secondarily inflamed and
ulcerated (Horne and Kawasaki, 1984; Horne 1986; Horne, 1996).
thickened epidermis and less dense internal tissue with dilated ves-
sels (Fig. 14c, d). The histological picture suggested the diagnosis of
condyloma acuminatum, a squamous lesion of the external genitalia
induced by Human Papilloma Virus (HPV).
Amplification of DNA allowed for the detection of HPV 18, a
strain with high oncogenic potential for some epithelial cancers
of the female genital tract. Cloning and sequencing of amplified
fragments confirmed the infection with HPV 18 and also revealed
the presence of JC9813 DNA, another HPV strain with low oncogenic
potential (Fornaciari et al., 2003).

3.1.5. Condyloma acuminatum from Naples (16th century)
The anthropogenic mummy of Maria of Aragon (1503–1568),
Marquise of Vasto, in the Basilica of S. Domenico in Naples, revealed
a small, pedunculated, branching skin neoformation of about
3 × 12 mm in the right paravulvar region (Fig. 14a). After rehydra-
tion, hematoxylin-eosin and Masson’s trichrome staining allowed
the observation of an exophytic papillary skin lesion (fig. 14b) with
3.1.6. Histiocytoma from Egypt
A dermal neoplasm was histologically observed on the skin of a
mummified left heel from a tomb generically attributed to Upper
Egypt (1290 BCE to 200 CE). One section of the skin showed a well-
circumscribed dermal mass composed of whorled, dark-staining
material. Masson’s trichrome staining revealed a small amount of
fine fibrous tissue within the lesion (Fig. 15) with positivity for

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Fig. 8. a, b: Large lacunae, surrounded by smaller round lacunae, destructing the

normal lamellar bone (Van Gieson, 50X; Hematoxylin Eosin, 30X); c: two lacu-
nae containing clusters of partially necrotic cells with solid epithelial-like aspects
(Hematoxylin Eosin, 60X).

Fig. 10. a: Pleomorphic, disintegrated cells surrounded by a delicate, fibrous stroma

(Hematoxylin Eosin, 200X); b: The cells reveal a shrunken cytoplasm and a marked
nuclear pleomorphism (HE, 600X) (courtesy of E. Gerszten).

iron stain and iron deposition confined to the lesion. The overly-
ing epidermis was necrotic. The dermal location, the features of
the lesion with its whorled appearance and the presence of iron
stain suggested a diagnosis of histiocytoma (Zimmerman, 1981).

3.2. Breast

3.2.1. Mammary fibroadenoma from Late Period Egypt

The Egyptian mummy known as PUM III (Pennsylvania Univer-
sity Museum III), belonging to a 35-year-old female and dating back
to approximately 835 BCE (Reyman and Peck, 1980), revealed a
small nodule of 1 cm in diameter in the lateral region of the left
breast. Through histology, it was revealed that the nodule was
not formed by connective tissue, but presented elements recogniz-
able as epithelial cells (Fig. 17a). The connective tissue contained
irregular cyst-like spaces, some of which presented large, partially
preserved cuboidal cells with recognizable nuclei (Fig. 17b). These
had the appearance of epithelial cells. The overall configuration and
residual microanatomy strongly suggested that this was a fibroade-
noma of the breast. The woman’s age, the size of the tumor, and its
lateral position in the breast supported this diagnosis (Reyman and
Peck, 1980).

Fig. 9. a: Brownish like-epithelial mass with a darker margin, looking like a pal- 3.3. Mammary fibroadenoma from Naples (16th century)
isade (arrows) (Van Gieson, 120X), separated from the bone by clefting artifacts
(Hematoxylin Eosin, 150X). Mammography, after breast rehydration, of the anthropogenic
mummy of Maria of Aragon (1503–1568), Marquise of Vasto, in

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Fig. 13. Papilloma virus from hand wart (EM, 300,000X; bar: 0.03 ␮m) (Horne,
1996).

the Basilica of S. Domenico in Naples, revealed a dense fibrous

tissue with cystic spaces and microcalcifications particularly evi-
dent in the right breast (Fig. 17a). Histology confirmed a dense
fibrous tissue with empty spaces and fibrous cyst walls, suggestive
of fibrocystic changes in advanced involution phase. Many single
and grouped microcalcifications, consisting of rounded basophilic
granules with a slightly eosinophil centre, were also evident. In
the upper outer quadrant of the right breast, two roundish forma-
Fig. 11. a: Marked hyperkeratosis with squamous papilloma (Phosphotungstic acid
tions of fibrous-hyaline connective tissue, with a diameter of about
Haematoxylin, 150X); b: solar keratosis (Heidenhein’s iron Hematoxylin, 300X).
1 and 0.8 cm respectively, suggested two hyaline fibroadenomas
(Fig. 18b) (Ventura et al., 2014).

3.4. Ovary

3.4.1. Ovarian cystadenoma from Egypt

A female mummy of the Ptolemaic Period was autopsied in 1825
by Granville, who concluded that “the disease which appears to have
destroyed her was ovarian dropsy attended with structural derange-
ment of the uterine system generally”. He also observed that the
uterus was larger than that of a 50–55-year-old woman, that there
was “a large sac connected with the left ovarium. . .”, that “the ovar-
ium and broad ligament of the right side are enveloped in a mass of
diseased structure. . .”, and that the right fallopian tube was nor-
mal (Granville, 1825). Fig. 1 of Plate XXII of Granville’s article is a
drawing that shows the right ovary and the parametrial tissues in
a confused mass of structures in continuity with the uterine body
(Fig. 19a). The upper part of what appears to be a “bulbous uterus”
emerges from behind these tangled structures. The left tube area is
shredded into three linear, strap-like structures terminating in two
rounded folds. A diagnosis of bilateral ovarian cystadenoma (or cys-
tadenocarcinoma) was consistent with this drawing (Aufderheide,
2003), but modern histology of this tumor showed no evidence
of malignancy, supporting the diagnosis of ovarian cystadenoma
(Fig. 19b) (Sandison and Tapp, 1998).

3.5. Ovarian cystadenoma from central Italy (19th century)

Among the natural mummies found in the Convent of S. George

Fig. 12. Thickened epidermis with hyperkeratosis, parakeratosis, mild acantho-
sis and vascular spaces, suggestive of verruca vulgaris (Hematoxylin Eosin, 200X)
(courtesy of E. Fulcheri).
of the Observants in Goriano Valli (L’Aquila, central Italy), the body
of a woman aged 43–50 years, dating back to the second half of
the 19th century, revealed the presence of a large neoformation
(approximately 10 cm in diameter) near the uterus in the abdom-
inal cavity. CT examination showed a cribrous mass in the right
iliac fossa and pelvis. Histology showed a large cystic neoplasm,

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Fig. 14. a: Small pedunculated, branching skin tumor at stereomicroscope (7X); b: Section of papillary tumor, with peduncle and dilated vessels (Masson’s trichromic, 5X);
c, d: exophytic papillary branch with thickened epidermis and dilated vessels (Masson’s trichromic, 50X, 70X).

partially solid, with fibrous walls and small papillary formations
partially covered by necrotic epithelium (Fig. 20). The macroscopic,
radiological and histological pictures allowed a diagnosis of ovar-
ian neoplasm, most probably a papillary cystadenoma, although it
was impossible to establish the grade of malignancy (Ventura et al.,
2006).
3.6. Urinary bladder
3.6.1. Vesical papilloma from Roman Period Egypt
Macroscopic examination of the bladder in an adult male
mummy from the Dakhleh Oasis, Egypt, dating back to the Roman
Period, showed a small papillary excrescence. Histology revealed
internal basophilic nuclear material and a reticulin stain. Small
clusters of cells surrounded by reticulin were consistent with an
epithelial tumor (Fig. 21). The diagnosis was an epithelial tumor,
in particular papilloma (or low-grade carcinoma) of the bladder
(Zimmerman and Aufderheide, 2010).
3.7. Nerve sheath
3.7.1. Neurilemmoma from Late Period Egypt
A large, smooth-walled and rounded cavity, moulded by the
pressure of a relatively hard, globular and lobulated tissue mass
growing in hour-glass shape, was observed outside the sacrum
(Fig. 22a) of an almost skeletonized female mummy of 35–45
years, dating back to the late 26th Dynasty (prior to 625 BCE).
Histology revealed bundles of spindle-shaped cells disposed in
collagenous stroma, showing nuclear palisading, sometimes in a
whorl-like pattern (Fig. 22b) or arranged in networks, suspended
in a myxoid or microcystic matrix, accompanied by blood vessels
with areas of hyalinization. Immunohistochemistry showed pos-
itivity for Glial Fibrillary Acidic Protein (GFAP) and for Epithelial
Membrane Antigen (EMA). At very high magnification by transmis-
sion electron microscopy (TEM), details of spindle-shaped tumor
cells were obtained. The macroscopic, radiographic, and histologi-
cal analysis allowed a diagnosis of neurilemmoma, a benign tumor
originating from a nerve sheath (Strouhal and Nemecková, 2004).
3.8. Adipose tissue
3.8.1. Lipoma from pre-Columbian Chile
The poorly preserved body of an adolescent 14-year-old male
from Northern Chile, dated to between 1100 and 1200 CE (Gerszten
et al., 2012), showed a subcutaneous mass of 4 × 4 × 2 cm, on
the right side of the chest, approximately 6 cm below the axilla
(Fig. 23a). Histology revealed conglomeration of mature adipose
tissue cells intermingling with fibrous septa (Fig. 23b). The micro-

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Table 2
Benign soft tissue tumors in mummies.

No. Tumor Provenance Dating Age in years/Sex References

1 Squamous skin papilloma Egypt Late Dynastic. adult/F Sandison (1967)

2 Verruca vulgaris Egypt ND adult/? Fulcheri (1987)
3 Verruca vulgaris Chile 15th century 8–9/M Horne and Kawasaki (1984), Horne (1996)
4 Condyloma acuminatum Naples 1568 65/F Fornaciari et al. (2003)
5 Histiocytoma Egypt 1290 BCE-200 CE adult/? Zimmerman (1981)
6 Angiokeratoma circumscriptum Chile 15th century 8–9/M Horne and Kawasaki (1986), Horne (1996)
7 Mammary fibroadenoma Egypt ca. 835 BCE 35/F Reyman and Peck (1980)
8 Mammary fibroadenoma Naples 1568 65/F Ventura et al. (2014)
9 Ovary cystadenoma Egypt Ptolemaic. 50–55/F Grenville (1825), Sandison and Tapp (1998)
10 Ovary cystadenoma Italy 19th century 45–50/F Ventura et al. (2006)
11 Vesical papilloma Egypt Roman. adult/M Zimmerman and Aufderheide (2010)
12 Neurilemmoma Egypt Late Dynastic. 35–45/F Strouhal and Nemecková (2004)
13 Lipoma Chile 110–1200 AD 14/M Gerszten and Allison (1991)

Fig. 16. Hyperkeratotic, acanthotic vascular lesion: The capillaries extend from the
epidermis, through the dermis, into subcutaneous adipose tissue. At right of plate,
the epidermis is ulcerated (Hematoxylin Eosin, 250X) (Horne and Kawasaki, 1992).

verrucae, one single case of condyloma, one squamous papilloma,

Fig. 15. Well-circumscribed dermal mass composed of whorled, dark-staining
material with small amount of fine fibrous tissue within the lesion, suggesting
histiocytoma (Hematoxylin Eosin, 40X) (courtesy of M. Zimmerman).
scopic features are those of a benign lipoma (Gerszten and Allison,
1991; Gerszten et al., 2012) (Table 2).
4. Conclusions
Thus far, there have only been 18 soft tissue neoplasms recorded
and histologically examined in mummified human remains. Only
five of these cases have been identified as malignant: three cases
of colorectal carcinomas, one basal cell carcinoma and one rhab-
domyosarcoma, with a prevalence of epithelial tumors. The other
cases are benign tumors, including as many as six skin tumors (two
one histiocytoma, and one angiokeratoma), two breast fibroadeno-
mas, two ovary cystadenomas, and single cases of urinary bladder
papilloma, neurilemmoma and lipoma.
The rarity of soft tissue tumors in paleopathology, espe-
cially malignant ones, is a highly debated problem (David and
Zimmerman, 2010). The most common types of bone tumors seen
in modern patients have been detected in ancient skeletal remains
(Capasso, 2005). However, the apparent paucity of ancient can-
cers of internal organs, such as lung, stomach, liver, prostate or
thyroid, that are so frequent in modern populations, needs some
consideration.
With regard to Egyptian mummies, it has been suggested
that the embalming practice of the Dynastic Period, which often
required the removal of the internal organs, did not allow for pale-
opathological diagnosis of visceral soft tissue neoplasms. However,
in the natural mummies (e.g. Predynastic and Roman Period Egyp-

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Fig. 17. a: Breast sample with nodule of connective tissue and without adipose
tissue, with elements recognizable as epithelial cells (Fig. 15a) (Weigert, 5X); b:
Irregular cyst like spaces, with large, partially preserved, epithelial cells with recog-
nizable nuclei (Fig. 15b) (Weigert, 200X) (Reyman and Peck, 1980). Fig. 18. a: Mammography with dense fibrous tissue, cystic spaces and microcalcifi-
cations in the right breast; b: In dense fibrous tissue and fibrous walls of cysts with
rare microcalcifications, two roundish formations of fibrous-hyaline connective, of
tian mummies, and the majority of South American mummies), about 1 and 0.8 cm in diameter, suggest two hyaline fibroadenomas (Hematoxylin
which maintain the internal organs, the relative scarcity of neo- Eosin, 10X).
plastic diagnoses requires a different explanation.
Tumoral proliferation, itself, could lead to severe alteration of
the tissues, making them more susceptible to rapid deterioration.
However, experimental studies about the effects of mummification
on neoplastic tissues and cells clearly demonstrated that malig-
nant tumors are histologically much better preserved than normal
organs (Zimmerman, 1977). For these reasons, the lack of evidence
in mummies could indicate a different occurrence in past societies.
The longer life span of modern populations can explain the high
incidence of cancer, which is the second leading cause of death in
modern developing countries, as a result of population aging (Torre
et al., 2015). On the contrary, the average age at death in past soci-
eties was considerably lower and death often arrived before cancer
could manifest itself (Capasso, 2005). Additionally, several risk fac-
tors such as cigarette smoke, pollution, chemical substances, drugs
and anthropogenic radiation related to modern industrial society,
have increasingly contributed to the current prevalence of cancer,
as many of these factors were not present in the pre-Modern era.
It should be noted that mummified remains are much rarer find-
ings than skeletal remains, but many Egyptian and South-American
mummies found in the course of the 19th and 20th centuries were
submitted to unscientific dissection without documented results.
The few paleopathological tumor diagnoses were obtained only
when autopsies of mummies were performed by a specialist in soft
tissue paleopathology (Aufderheide, 2003).
The most recent studies on mummies have been conducted with
non-invasive methods. Unfortunately, the diagnosis of soft tissue
tumors is extraordinarily difficult on the basis of only radiologi-
cal and endoscopic examination; moreover, lesions suggestive of Fig. 19. a: Macroscopic aspect of bilateral cystadenoma of ovary (Granville, 1825);
malignant tumors still require confirmation by histology. For this b: Wall of the ovarian cystic tumor of Granville’s mummy, with rounded remains of
reason, the small series of Renaissance mummies from Naples, the papillary projections (Sandison and Tapp, 1998) (Hematoxylin Eosin, 160X).

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Fig. 20. Fibrous wall of partially solid, large cystic neoplasm, with small papillary
formations partially covered by necrotic epithelium (Hematoxylin Eosin, 100X).

composed of eleven adults (10 males and only 1 female) (Fornaciari,

2006) with three cases of cancer in individuals between 55 and 71
years of age, is particularly important. Despite the limited num-
ber of examined individuals, the cancer prevalence of 33.3% in this
small group is similar to that of 30.9% we find in more developed
Fig. 21. Wall of urinary bladder with small papillary transitional cell papilloma
modern countries (Torre et al., 2015). As a result, we can conclude (Hematoxylin Eosin, 40X) (courtesy of E. Gerszten).
that probably, at least in some particular environmental and age
conditions as in this series of Spanish nobles interred in Naples,
of damaged or partial mummies, under the supervision of a com-
cancer in the past must have been frequent.
petent paleopathologist, paying maximum attention to any small
In conclusion, even if mummy autopsies have been avoided in
sign of neoplastic disease. I am convinced that in this manner, the
the last decades for their destructive character, it may still be ben-
number of known ancient soft tissue tumors will increase greatly.
eficial and possible to perform them without problems in cases

Fig. 22. a: X-ray of sacrum showing oval cavities in right half of the second segment and a large and minor cavities cavity in left half of the second and third segment;
b: Bundles of spindle-shaped cells arranged in collagenous stroma showing nuclear palisading, in whorl-like pattern (white triangle) (Toluidine blue, 200X) (Strouhal and
Nemecková, 2004).

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Fig. 23. a: Subcutaneous mass on the right side of the thorax. b: Conglomeration of
mature adipose tissue cells in fibrous septa (Hematoxylin Eosin, 60X).
Funding
None.
References
Allison, M.J., Gerszten, E., 1982. Paleopathology in South American Mummies.
Virginia Commonwealth University, Richmond, pp. 39–74.
Aufderheide, A.C., 2003. The Scientific Study of Mummies. Cambridge University
Press, Cambridge.
Bruner, J.M., Connelly, J.H., Saya, H., 1993. p53 protein immunostaining in routinely
processed paraffin-embedded sections. Mod. Pathol. 6, 189–194.
Capasso, L., 2005. Antiquity of cancer. Int. J. Cancer 113, 2–13.
Crowson, A.N., 2006. Basal cell carcinoma: biology, morphology and clinical
implications. Mod. Pathol. 19 (Supplement), 127–147.
David, R., Zimmerman, R., 2010. Cancer: an old disease, a new disease or
something in between? Nat. Rev. Cancer 10, 728–733.
Fornaciari, G., Giuffra, V., 2012. Soft tissue tumors in palaeopathology: A review.
Pathobiology 79, 257–267.
Fornaciari, G., Bruno, J., Corcione, N., Tornaboni, D., Castagna, M., 1989. Un cas de
tumeur vmaligne primitive de la règionnaso-orbitaire dans une momie de la
basilique de S. Domenico Maggiore à Naples (XVIe siècle). In: Capasso, L. (Ed.),
Advances in Paleopathology: Proceedings of the VII European Meeting of the
Paleopathology Association. Chieti, Solfanelli Editore, pp. 65–69.
Fornaciari, G., Marchetti, A., Pellegrini, S., Ciranni, R., 1999. K-ras mutation in the
tumour of king Ferrante I of Aragon (1431–1494) and environmental mutagens
at the Aragonese court of Naples. Int. J. Osteoarchaeol. 9, 302–306.
Fornaciari, G., Zavaglia, K., Giusti, L., Vultaggio, C., Ciranni, R., 2003. Human
papillomavirus in a 16th century mummy. Lancet 362, 1160.
Fornaciari, G., 1993. Adenocarcinoma in the mummy of Ferrante I of Aragon, King
of Naples (1431–1494). Paleopathol. Newsl. 82, 5–8.
Fornaciari, G., 2006. Le mummie aragonesi in San Domenico Maggiore di Napoli.
Med. Secoli 18, 843–864.
Please cite this article in press as: Fornaciari, G., Histology of ancient soft tissue tumors: A review. Int. J. Paleopathol. (2017),
http://dx.doi.org/10.1016/j.ijpp.2017.02.007
13
Fornaciari, G., 2008. Food and disease at the Renaissance courts of Naples and
Florence: a paleonutritional study. Appetite 51, 10–14.
Fulcheri, E., 1987. Case no. 27: verruca vulgaris. Paleopathol. Club Newsl. 31, 2.
Gaeta, R., Giuffra, V., Fornaciari, G., 2013. Atherosclerosis in the Renaissance elite:
Ferdinand I King of Naples (1431–1494). Virchows Arch. 462, 593–595.
Gaeta, R., Ventura, L., Fornaciari, G., 2015. Il tumore di Ferdinando Orsini, duca di
Gravina di Puglia (+ 1549). In: Atti del 50◦ Congresso Nazionale della Società
Italiana di Storia della Medicina, Palermo 2–4 Ottobre 2014, Palermo,
Seristampa, pp. 189–194.
Gerszten, E., Allison, M., 1991. Human soft tissue tumors in Paleopathology. In:
Ortner, D.J., Aufderheide, A.C. (Eds.), Human Paleopathology: Current Syntheses
and Future Options. Smithsonian Institute, Washington, pp. 260–277.
Gerszten, E., Allison, M., Maguire, B., 2012. Paleopathology in South American
mummies: a review and new findings. Pathobiology 79, 247–256.
Granville, A.B., 1825. An essay on Egyptian mummies; with observations on the art
of embalming among the ancient Egyptians. Philos. Trans. R. Soc. Lond. 115,
269–316.
Horne, P.D., Kawasaki, S.Q., 1984. The prince of El Plomo: a paleopathological
study. Bull. N. Y. Acad. Med. 60, 925–931.
Horne, P.D., 1986. Case no. 23: Angiokeratoma circumscription. Paleopathol. Club
Newsl. 27, 1.
Horne, P.D., 1996. The prince of El Plomo: a frozen treasure. In: Spindler, K.,
Wilfing, H., Rastbichler-Zissenig, E., zur Nedden, D., Nothdurfter, H. (Eds.), The
Man in the Ice, Volume 3. Human Mummies: A Global Survey of Their Status
and Techniques of Conservation. Springer, Wien, New York, pp. 153–157.
Hunt, et al. Meta-analysis of published paleo-oncological data in modern homo
sapiens upuntil 1900 CE. This issue.
Kuhnle, G.G., Bingham, S.A., 2007. Dietary meat, endogenous nitrosation and
colorectal cancer. Biochem. Soc. Trans. 35, 1355–1357.
Marchetti, A., Pellegrini, S., Bevilacqua, G., Fornaciari, G., 1996. K-Ras mutation in
the tumour of Ferrante I of Aragon, King of Naples. Lancet 347, 1272.
Ottini, L., Falchetti, M., Marinozzi, S., Angeletti, L.R., Fornaciari, G., 2011.
Gene-environment interactions in the pre-industrial Era: the cancer of King
Ferrante I of Aragon (1431–1494). Hum. Pathol. 42, 332–339.
Paracelsus, A.T.P., 1573. Chirurgia Minor. Ex Versione Gerardi Dorn., pp. 248–263.
Radzikowska, J., Kukwa, W., Kukwa, A., Czarnecka, A., Krzeski, A., 2015.
Rhabdomyosarcoma of the head and neck in children. Contemp. Oncol. (Pozn.)
19, 98–107.
Reyman, T.A., Dowd, A.M., 1980. Processing of mummified tissue for histological
examination. In: Cockburn, A., Cockburn, E. (Eds.), Mummies, Disease and
Ancient Cultures. Cambridge University Press, Cambridge, pp. 258–273.
Reyman, T.A., Peck, W.H., 1980. Egyptian mummification with evisceration per
ano. In: Cockburn, A., Cockburn, E. (Eds.), Mummies, Disease and Ancient
Cultures. Cambridge University Press, Cambridge, pp. 85–100.
Riddle, J.M., 1980. A survey of ancient specimens by electron microscopy. In:
Cockburn, A., Cockburn, E. (Eds.), Mummies, Disease and Ancient Cultures.
Cambridge University Press, Cambridge, pp. 275–286.
Rosai, J., 1996. Ackerman’s Surgical Pathology, vol. 1., eighth edition Mosby-Year
Book, Inc., pp. 754–777, St. Louis, Missouri, Mosby.
Ruffer, M.A., 1910. Remarks on the histology and pathological anatomy of Egyptian
mummies. Cairo Sci. J. 10, 3–7.
Saffhill, R., Margison, G.P., O’Connor, P.J., 1985. Mechanisms of carcinogenesis
induced by alkylating agents. Biochim. Biophys. Acta 832, 111–145.
Sandison, A.T., Tapp, E., 1998. Disease in ancient Egypt. In: Cockburn, A., Cockburn,
E., Reyman, T.A. (Eds.), Mummies, Disease and Ancient Cultures. Cambridge
University Press, Cambridge, pp. 38–58.
Sandison, A.T., 1955. The histological examination of mummified material. Stain
Tech. 30, 277–283.
Sandison, A.T., 1967. Diseases of the skin. In: Brothwell, D.R., Sandison, A.T. (Eds.),
Diseases in Antiquity. Springfield, Thomas, pp. 449–463.
Strouhal, E., Nemecková, A., 2004. Paleopathological find of a sacral
neurilemmoma from ancient Egypt. Am. J. Phys. Anthropol. 125, 320–328.
Strouhal, E., 1994. Malignant tumors in the Old World. Paleopathol. Newsl. 85
(Supplement), 1–6.
Torre, L.A., Bray, F., Siegel, R.L., Ferlay, J., Lortet-Tieulent, J., Jemal, A., 2015. Global
cancer statistics, 2012. Cancer J. Clin. 65, 87–108.
Ventura, L., Miranda, G., Mercurio, C., Ciocca, F., Fornaciari, G., 2006.
Paleopathology of the natural mummies of the inner Abruzzo region
(XVIII–XIX century). Med. Secoli 18, 875–896.
Ventura, L., Gaeta, R., Giuffra, V., Mercurio, C., Pistoia, M.L., Cicozzi, A., Castagna, M.,
Fornaciari, G., 2014. Breast pathology in ancient human remains. An approach
to mummified mammary gland by modern investigation methods. Congresso
Annuale di Anatomia Patologica SIAPEC-IAP. Pathologica106, 216–218.
Weichert, K.A., Bove, K.C., Aron, B.S., Lampkin, B., 1976. Rhabdomyosarcoma in
children: A clinicopathologic studyof 35 patients. Am. J. Clin. Pathol. 66,
692–701.
Zimmerman, M.R.A., Aufderheide, A.C., 2010. Seven mummies of the Dakhleh
oasis, Egypt: seventeen diagnoses. Paleopathol. Newsl. 150, 16–23.
Zimmerman, M.R.A., 1977. An experimental study of mummification pertinent to
the antiquity of cancer. Cancer 40, 1358–1362.
Zimmerman, M.R.A., 1981. A possible histiocytoma in an Egyptian mummy. Arch.
Dermatol. 117, 364–365.