J Cutan Pathol 2009: 36: 675–679doi: 10.1111/j.1600-0560.2008.01094.xJohn Wiley & Sons. Printed in Singapore

Copyright # 2009 John Wiley & Sons A/S

Journal of

Cutaneous Pathology

Peritoneal mesothelioma presenting asa skin nodule

Mesothelioma is a malignancy of the pleura, pericardium andperitoneum that is rarely seen in cutaneous biopsies. We present a caseof a 75-year-old man with significant occupational exposure to asbestoswho developed peritoneal mesothelioma that presented as a skinnodule in an old appendectomy scar. The patient presented witha complaint of increased hardness along his appendectomy scar.Physical examination revealed an anterior abdominal wall massoverlying the appendectomy scar, which was subsequently biopsied.Histologic examination of the abdominal wall mass revealed aninfiltrating epithelioid and papillary neoplasm within the dermis andsubcutaneous tissue. Immunohistochemical stains showedimmunoreactivity for cytokeratin (CK) 7, CK 5/6, calretinin andvimentin. CK 20, monoclonal carcinoembryonic antigen, prostate-specific antigen and prostate-specific acid phosphatase were negative.The profile supported the diagnosis of mesothelioma. Cutaneouspresentation of mesothelioma is rare but should be considered in thedifferential diagnosis of patients with significant asbestos exposure.

Abban C, Viglione M. Peritoneal mesothelioma presenting as a skinnodule.J Cutan Pathol 2009; 36: 675–679. # 2009 John Wiley & Sons A/S.

Cynthia Abban1 andMichael Viglione2

1Department of Microbiology andImmunology, Chicago Medical School,Rosalind Franklin University of Medicine andScience, North Chicago, IL, USA and2Department of Pathology, Lake ForestHospital, Lake Forest, IL, USA

Michael Viglione, MD, PhD, Department ofPathology, Lake Forest Hospital, 660 North,Westmoreland Road, Lake Forest, IL 60045, USATel: (847) 535 6287Fax: (847) 535 6237e-mail: mpviglione@aol.com

Accepted for publication June 2, 2008

Malignant mesothelioma is a tumor that arises fromthe cells lining the pleura, pericardium, peritoneumand the rete testis, and themajority of cases are relatedto asbestos exposure.1,2 Rare spontaneous caseswithout an obvious link to asbestos and rare casessecondary to irradiation have been reported.3 Anunusual aspect of mesothelioma is the 20- to 40-yearlatency between exposure and development ofdisease.4 There has been an increase inmesotheliomaover the past 20 years with the current incidence inthe USA ranging from 7 to 40 per million; the in-cidence is expected to continue to rise until approxi-mately 2020.4,5

The long latencyperiodmight suggest a complicatedandmultistep pathway between asbestos exposure andthe development of mesothelioma. The fibers areinhaled or swallowed and subsequently transported tothe pleural or peritoneal surfaces where they act asa complete carcinogen with malignancy occurring insequential stages of initiation and promotion. Studies

have shown that asbestos fibers produce effects viadirect interaction with mesothelial cells and indirecteffects related to ingestion by macrophages. The fiberscan interact with the DNA in the mesothelial cellsresulting in chromosomal abnormalities, the mostcommon being monosomy 22. Rearrangements of 1p,3p, 9p and 6q are also common abnormalities.Deletion of tumor suppressor genes has also beenobserved in cell lines exposed to asbestos.Macrophagesthat have phagocytized asbestos secrete elevated levelsof hydroxyl radicals.6

Peritonealmesothelioma tends to present late in thedisease course as the presenting symptoms are oftendelayed and vague. Presenting symptoms can includeabdominal pain, ascites, weight loss and bowelobstruction. Our patient presented with a complaintof protracted abdominal pain and a recent hardeningof his appendectomy scar.

In this study, we report a case of peritonealmesothelioma presenting as a skin nodule in an old

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scar. Cutaneous presentation of mesothelioma isuncommon with most cases occurring as either directextension to the skin7 or metastasis to the skin.7,8

Clinically, cutaneousmesotheliomahas been reportedto present as an erythematous eruption, violaceouspapules and skin nodules.7,9,10

Case report

A 75-year-old man presented to his physiciancomplaining of recurrent abdominal pain over thepast year and increasing hardness along his appen-dectomy scar. His medical history was significant foran appendectomy approximately 50 years ago, cys-toscopic surgery for bladder carcinoma 5 years beforepresentation and a subtotal colectomy for recurrentdiverticulitis 2 years prior, after which he developedan incisional hernia. The patient had significantasbestos exposure during his military service inWorldWar II.

Physical examination revealed an anterior abdom-inal wall mass overlying the appendectomy scar withmarked firmness and reddish-blue discoloration of theskin. Multiple shotty nodes in the right groin couldalso be palpated. During a routine exam 3 monthsprior, no abdominal wall mass had been detected. Acomputerized tomography (CT) scan of the abdomenand pelvis showed diffuse nodular disease in hisabdomen with herniation of the caked omentum intothe umbilical region, severe ascites in the abdominaland pelvic cavities as well as seeding of theperitoneum. Multiple lesions involving the serosalsurfaces of the distal small bowel loops and sigmoidcolon were also detected (Fig. 1). The lower lung lobebases showed emphysematous changes with extensivecalcifications of the anterior right diaphragmaticpleura unchanged from a CT 2 years prior.

An excisional biopsy of the abdominal wall masswas performed. Histologic and immunohistochemi-cal evaluation of the tumor established the diagnosisof peritoneal mesothelioma. A course of hospitaliza-tion followed and the patient succumbed to themesothelioma within 6 months of diagnosis.

Results

A 2.7 3 2.0 3 1.0 cm nodule with overlying skinwas excised from the anterior abdominal wall in thearea of the old appendectomy scar. The mass wassectioned and examined using routine formalin-fixed,paraffin-embedded tissue.Thehematoxylin and eosinsections showed an infiltrating papillary neoplasmwithin the dermis and subcutaneous tissue. Thetumor infiltrated as small cords and nests with focalglandular differentiation. The nuclei were pleomor-phic with open chromatin, prominent nucleoli and

occasional mitotic figures. The papillary growthpattern was best seen in areas in which the tumorinvaded into the subcutaneous tissue. Foci of epithe-lioid cytology were also observed (Fig. 2A–C).Immunohistochemical stains were performed on

deparaffinized 4 mMsections (Fig. 3). Dako antibodieswere utilized at the following dilutions: cytokeratin(CK) 7 (1 : 50), CK 5/6 (1 : 50), vimentin (1 : 400),calretinin (1 : 50), prostate-specific acid phosphatase(PSAP) (1 : 200), prostate-specific antigen (PSA)(1 : 200), monoclonal carcinoembryonic antigen(CEA) (1 : 100) and CK 20 (1 : 100). Table 1summarizes the results of immunohistochemicalanalysis. The cells stained positive for CK 7, CK 5/6, vimentin and calretinin. The tumor cells werenegative for PSAP, PSA, CEA and CK 20.

Discussion

Mesothelioma is a malignancy of the lining of thelungs and the peritoneal cavity that is rarely seen incutaneous biopsies. Whenmesothelioma does involvethe skin, it is usually through direct extension ormetastasis.7,9–11 Cutaneous mesothelioma has alsobeen reported following a fine needle aspiration.12

This report is unusual in that the peritonealmesothelioma involved an old surgical scar and theresulting nodule prompted the patient to seekmedicalattention. The biopsy of the scar provided thediagnosis for the patient’s widespread malignancy.

Fig. 1. Computerized tomography scan of the abdomen and pelvis

showed extensive carcinomatosis with omental caking and perito-

neal seeding (note bright nodules on scan). Severe ascites of the

abdominal and peritoneal cavities was noted. Serosal lesions were

also noted on the distal small bowel loops and sigmoid colon.

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Mesothelioma typically consists of two types ofcells, epithelial or mesenchymal, and the tumor showsa predominance of one cell type or the other.13 Thebiopsy from this patient showed a papillary growth

with organoid differentiation and would therefore beclassified as an epithelial type mesothelioma.

Peritoneal mesothelioma is a less common form ofthe disease, accounting for 10–20% of mesothelio-mas.14 Clinically, there are two types of peritonealmesothelioma, wet and dry-painful type.15 In the wettype, there is ascites with little or no evidence of a solidtumor on CT. Sometimes small nodules lining theparietal peritoneal surface are evident. The dry-painful type does not produce ascites but displaysmass lesions, often with a dominant mass, isolated toone part of the abdomen resulting in pain. In this case,the patient presented with CT findings of ascites,which is a common sign of most cases of peritonealmesotheliomas comparedwith other intra-abdominalmalignancies,15,17 and our patient would be consid-ered to have the wet form of peritonealmesothelioma.

Epithelioid mesothelioma can be difficult to diag-nose, especially in skin biopsies, because of the widevariation of histologic differentiation. Histologicfeatures could include trabecular cords of cuboidaland polygonal epithelial cells, focal glandular andpapillary appearances which all mimic characteristicsof carcinomas. Thus, colorectal adenocarcinoma,renal cell carcinoma, prostatic adenocarcinoma,angiosarcoma and lung adenocarcinoma would beincluded in the histologic differential diagnosis ofmesothelioma. Accordingly, immunohistochemistryplays a central role in the diagnosis. In our study, themesotheliomawas immunoreactive for calretinin,CK7 and CK 5/6. Wilm’s tumor 1, mesothelin-1 andHBME-1 are additional markers known to be positivein these tumors.18 Calretinin is regarded as being oneof the most sensitive and specific of the mesotheliomamarkers. It stains both the nucleus and the cytoplasmstrongly and diffusely and is frequently expressed in allhistologic types of mesothelioma.15,18 Given thepatient’smedical history, age and sex, it was importantto exclude other malignancies, especially bladder,colon and lung adenocarcinoma. Accordingly, thetumor in our study was negative for CK 20, PSA,PSAP, thyroid transcription factor-1 and CEA.

In some cases, electron microscopy (EM) can bea powerful adjunct in establishing the diagnosis of

Fig. 2. Hematoxylin and eosin appearance of cutaneous mesothe-

lioma. A) Infiltration of papillary and reticular dermis by

mesothelioma (34). B) Papillary growth pattern seen in an area

of subcutaneous invasion (340). C) Solid/nested growth pattern

intercalating among dermal collagen (340).

Table 1. Immunohistochemistry results

Immunostain Result

CK 7 PositiveCK 5/6 PositiveVimentin PositiveCalretinin PositivePSAP NegativePSA NegativeCEA (monoclonal) NegativeCK 20 Negative

CEA, carcinoembryonic antigen; CK, cytokeratin; PSA, prostate-specificantigen; PSAP, prostate-specific acid phosphatase.

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mesothelioma by highlighting the long microvilli andabundant tonofilaments characteristic of thistumor.13,19 Only formalin-fixed tissue was availablefor examination of our patient’s tissue, precluding EMexamination.

Conclusion

Malignant mesothelioma is an uncommon tumorarising from the serosal membranes with 10–20%occurring in the peritoneal cavity.14 There are onlyrare reports of peritoneal7 or pleural9 mesotheliomainvolving the skin usually because of cutaneousextension or distant metastasis10 with one report ofpleural mesothelioma involving chest wall scars.9

However, it is not uncommon for gastrointestinalmalignancies to extend around surgical scars.20

Cutaneous involvement by visceral cancers has beenreported to occur in 0.7–9% of patients and isgenerally a late occurrence in the disease process.Ourcase is unusual in that the cutaneous manifestationwas one of the presenting symptoms. Breast carci-noma accounts for most primary tumors seen in theskin, followed by melanoma, mucosal carcinomas ofthe head and neck, lung carcinoma and coloncarcinoma.21

The patient’s history of asbestos exposure alongwith histologic features of epithelioid mesotheliomaand an appropriate immunohistochemical profileestablished the diagnosis of peritoneal mesotheli-oma. In our case, the unique feature is that thecutaneous nodule of mesothelioma led the patient toseek medical attention and ultimately provided themeans for diagnosis. Mesothelioma should beconsidered in the differential diagnosis of skintumors, especially in older individuals with potentialexposure to asbestos.

Acknowledgements

The authors would like to thank Dr. Stephen Ganshirt for his

assistance in providing clinical information and access to the

patient’s medical records.

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