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Year : 2017  |  Volume : 60  |  Issue : 1  |  Page : 102-104
Malignant melanocytic neoplasm of pancreas with liver metastasis: Is it malignant melanoma or clear cell sarcoma?

1 Department of General Pathology, Christian Medical College, Vellore, Tamil Nadu, India
2 Department of Surgery, Christian Medical College, Vellore, Tamil Nadu, India
3 Department of Medical Oncology, Christian Medical College, Vellore, Tamil Nadu, India

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Date of Web Publication14-Feb-2017


Malignant melanocytic neoplasm, usually seen in soft tissues, is rare in a visceral location and presents as a diagnostic dilemma. We present a case of pancreatic malignant melanocytic neoplasm with liver metastasis. A 58-year-old man presented with left upper abdominal swelling and loss of appetite. Imaging revealed a large mass arising from the pancreatic tail, and this was diagnosed as malignant neoplasm with melanocytic differentiation on biopsy with the possible differentials of malignant melanoma, clear cell sarcoma (CCS), and perivascular epithelioid cell neoplasm. The patient underwent distal pancreatectomy and splenectomy for the same. Follow-up imaging 6 months later showed a metastatic liver lesion, for which he also underwent a liver resection. BRAF mutational analysis was found to be negative. Both CCS and malignant melanoma have similar morphological features and melanocytic differentiation, but each harbors a distinct genetic background. Differentiation of both has diagnostic and therapeutic implications.

Keywords: Clear cell sarcoma, malignant melanoma, mutation analysis, pancreas

How to cite this article:
Kodiatte TA, George SV, Chacko RT, Ramakrishna B. Malignant melanocytic neoplasm of pancreas with liver metastasis: Is it malignant melanoma or clear cell sarcoma?. Indian J Pathol Microbiol 2017;60:102-4

How to cite this URL:
Kodiatte TA, George SV, Chacko RT, Ramakrishna B. Malignant melanocytic neoplasm of pancreas with liver metastasis: Is it malignant melanoma or clear cell sarcoma?. Indian J Pathol Microbiol [serial online] 2017 [cited 2021 Jun 22];60:102-4. Available from: https://www.ijpmonline.org/text.asp?2017/60/1/102/200054

   Introduction Top

Clear cell sarcoma (CCS), also known as melanoma of soft parts, preferentially affects young adults and typically arises in the deep soft tissues of the lower extremities.[1] The histological similarity and the immunohistochemical overlap pose a challenge in diagnosing and distinguishing CCS from metastatic melanoma (MM).[2] A pancreatic location is rare [2] and we present a case of malignant melanocytic neoplasm of pancreas in a 58-year-old male who was clinically suspected to have carcinoma and radiologically diagnosed as pancreatic endocrine tumor.

   Case Report Top

A 58-year-old male presented with complaints of left upper abdominal swelling, early satiety and loss of appetite and weight of 2 months duration. Routine laboratory results were within normal limits. Computed tomographic (CT) examination revealed a 14 cm × 12 cm large heterogeneous left anterior pararenal space mass, probably arising from the pancreatic tail and invading the splenic hilum. Clinically, he was suspected to have pancreatic carcinoma and radiologically diagnosed as pancreatic endocrine tumor. Initial ultrasound-guided needle biopsy from the pancreatic mass was diagnosed as malignant neoplasm with melanocytic differentiation, based on positivity for HMB45 and Melan A and negativity for epithelial and neuroendocrine markers. Following the biopsy report, the patient was extensively examined for cutaneous and ocular lesions, but no lesions were detected. Subsequently, the patient underwent distal pancreatectomy and splenectomy. Peroperatively, a 18 cm × 10 cm highly vascular tumor was seen arising from the tail of the pancreas, densely adherent to the spleen and mesentery of the splenic flexure. Grossly, the pancreas was replaced by a large circumscribed tumor measuring 18 cm × 11.5 cm × 18 cm with a variegated, hemorrhagic, and necrotic cut surface [Figure 1]a and [Figure 1]b. Histologically, the tumor was composed of closely packed solid nests of large polygonal cells with abundant granular eosinophilic cytoplasm, round to oval pleomorphic hyperchromatic nuclei, prominent nucleoli, exhibiting bizarre and multinucleate forms and scattered mitotic activity including atypical forms [Figure 2]a and [Figure 2]b. The tumor cells in foci contained a brownish black pigment which was removed by melanin bleach [Figure 2]c. There were large areas of necrosis and infarction. Focal lymphovascular invasion was present. The tumor cells showed strong cytoplasmic positivity for HMB45, S-100 and Melan A with an MIB-1 index of 60%–70% [Figure 3]a, [Figure 3]b, [Figure 3]c. The tumor cells were negative for epithelial, neuroendocrine and smooth muscle markers, and CD117. A diagnosis of MM of soft parts/CCS was given. There was no infiltration into adjacent pancreas, adipose tissue, spleen, or lymph nodes. A positron emission tomography (PET)-CT done 2 weeks later showed a 1.5 cm × 1.5 cm peripherally enhancing lesion in the segment two-third of liver. Four weeks later, he underwent a left lateral liver segmental resection and histologically, there was a metastatic tumor with similar morphology and focal microvascular invasion. During the next 6 months, the patient received six cycles of temozolomide. The subsequent PET-CT scan showed a metabolically active recurrent focus in the distal end of pancreas with a metastatic deposit in the right lateral segment of liver suggestive of disease progression. BRAF mutational analysis was found to be negative. EWSR1-ATF1 and EWSR1-CREB1 fusion mutation analyses were not done. The patient was lost to follow-up later.
Figure 1: (a and b) Circumscribed tumor with a variegated, hemorrhagic and necrotic cut surface

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Figure 2: (a) Solid nests of large polygonal cells with eosinophilic cytoplasm and varying sized round to oval hyperchromatic nuclei (H and E, ×200). (b) Tumor cells with abundant eosinophilic granular cytoplasm and large pleomorphic nuclei with prominent nucleoli and exhibiting mitosis (red arrow) (H and E, ×400). (c) Tumor cells containing brownish black melanin pigments (H and E, ×400)

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Figure 3: (a) Tumor cells showing strong cytoplasmic staining for HMB 45 (IHC, ×200). (b) Tumor cells showing cytoplasmic staining for Melan A (IHC, ×200). (c) Tumor cells showing nuclear and cytoplasmic staining for S 100 (IHC, ×200)

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   Discussion Top

Enzinger coined the term CCS of tendons and aponeuroses in 1965 and 1983 along with Chung, documented the melanocytic phenotype of the tumor and proposed the term MM of soft parts.[3] Adolescents and young adults comprise the most common age group affected with no particular gender bias.[4] These tumors commonly occur in the tendons, fascia, and aponeuroses and mostly present as a slow-growing and frequently painful soft tissue mass. Although the most frequently involved sites are foot and ankle, rare cases presenting in the visceral organs have been reported.[2],[4] A pancreatic location is extremely rare and a few isolated cases have been reported.[2] The visceral CCSs show a male predominance, present at a later age and have a worse prognosis than soft tissue CCS.[5] CCS of the soft tissues most commonly shows lung, bone, and lymph node metastases, whereas CCS of the gastrointestinal tract typically shows lymph node and liver metastases.[1],[6]

CCS is characterized by a nested/fascicular growth of clear cells displaying phenotypic features shared with MM including the presence of melanin, ultrastructural evidence of melanosomes, and the immunohistochemical expressions of S-100, HMB-45, Melan-A, and microphthalmia transcription factor. CCS is consistently associated with a specific recurrent t(12;22)(q13;q12) translocation, leading to the formation of the EWSR1-ATF1 fusion transcript.[5] Another variant fusion gene EWSR1-CREB1 resulting from a chromosomal translocation t(2;22)(q34;q12) has been found in a subset of CCS. In contrast to most melanomas, they lack BRAF mutations.[1] Thus, a firm diagnosis of CCS relies mainly on cytogenetic or molecular diagnostic studies by the demonstration of the EWSR1-ATF1 or EWSR1-CREB1 fusions and the lack of BRAF mutations.[7]

The other histological differential diagnoses of nested epithelioid malignancies include epithelioid malignant peripheral nerve sheath tumor (MPNST), epithelioid gastrointestinal stromal tumor (GIST), perivascular epithelioid cell neoplasm (PEComa), CCS like tumor of the gastrointestinal tract” (CCSLTGT)/”gastrointestinal neuroectodermal tumour” (GNET), granular cell tumor (GCT), alveolar soft part sarcoma (ASPS), and rarely metastatic renal cell carcinomas. MPNST, GCT, and ASPS lack expression of HMB-45 and Melan-A. Epithelioid GISTs are usually CD117 and DOG1 positive. PEComas show a co-expression of SMA and melanocytic markers with the absence of S100 expression.[7] CCSLTGT/GNET may be distinguished from CCS involving the gastrointestinal tract and MM by its distinctive morphological features, including the presence of osteoclast-like giant cells, pseudopapillary and sheet-like growth patterns, SOX-10 expression, and absent expression of melanocytic markers.[7],[8]

Correct identification of CCS and MM is important for the diagnostic workup and treatment options available which can help customize the adjuvant systemic nonsurgical modalities. Recent studies have suggested that complete surgical resection with adjuvant radiotherapies and/chemotherapies may be of value in the treatment of CCS. Therapeutic strategies for MM involving the GI tract would consist of surgical resection and immunotherapy with or without combination chemotherapy including BRAF inhibitors such as vemurafenib and c-KIT inhibitors.[3],[8],[9],[10]

   Conclusion Top

Malignant melanocytic neoplasm in a visceral location presents itself with diagnostic difficulties. Both CCS and MM have similar morphological features and melanocytic differentiation but each harbors a distinct genetic background. This has implications for the diagnostic workup and treatment.

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Conflicts of interest

There are no conflicts of interest.

   References Top

Kraft S, Antonescu CR, Rosenberg AE, Deschler DG, Nielsen GP. Primary clear cell sarcoma of the tongue. Arch Pathol Lab Med 2013;137:1680-3.  Back to cited text no. 1
Covinsky M, Gong S, Rajaram V, Perry A, Pfeifer J. EWS-ATF1 fusion transcripts in gastrointestinal tumors previously diagnosed as malignant melanoma. Hum Pathol 2005;36:74-81.  Back to cited text no. 2
Chung EB, Enzinger FM. Malignant melanoma of soft parts. A reassessment of clear cell sarcoma. Am J Surg Pathol 1983;7:405-13.  Back to cited text no. 3
Dim DC, Cooley LD, Miranda RN. Clear cell sarcoma of tendons and aponeuroses: A review. Arch Pathol Lab Med 2007;131:152-6.  Back to cited text no. 4
Lyle PL, Amato CM, Fitzpatrick JE, Robinson WA. Gastrointestinal melanoma or clear cell sarcoma? Molecular evaluation of 7 cases previously diagnosed as malignant melanoma. Am J Surg Pathol 2008;32:858-66.  Back to cited text no. 5
Plesec TP. Gastrointestinal mesenchymal neoplasms other than gastrointestinal stromal tumours: Focusing on their molecular aspects. Pathol Res Int 2011;2011:952569.  Back to cited text no. 6
Kosemehmetoglu K, Folpe AL. Clear cell sarcoma of tendons and aponeuroses, and osteoclast-rich tumour of the gastrointestinal tract with features resembling clear cell sarcoma of soft parts: A review and update. J Clin Pathol 2010;63:416-23.  Back to cited text no. 7
Kelly ED, Rubin BP, Goldblum JR. Mesenchymal tumours of the gastrointestinal tract. In: Odze RD, Goldblum JR, editors. Surgical Pathology of the GI Tract, Liver, Biliary Tract, and Pancreas. 3rd ed. China: Elsevier Saunders; 2015. p. 843-4.  Back to cited text no. 8
Coit DG, Thompson JA, Andtbacka R, Anker CJ, Bichakjian CK, Carson WE, 3rd, et al. Melanoma, version 4.2014. J Natl Compr Canc Netw 2014;12:621-9.  Back to cited text no. 9
Tarhini AA, Pahuja S, Kirkwood JM. Neoadjuvant therapy for high-risk bulky regional melanoma. J Surg Oncol 2011;104:386-90.  Back to cited text no. 10

Correspondence Address:
Dr. Banumathi Ramakrishna
Department of General Pathology, Christian Medical College, Vellore - 632 004, Tamil Nadu
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0377-4929.200054

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