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Journal of Cancer Research and Therapeutics
Medknow Publications on behalf of the Association of Radiation Oncologists of India (AROI)
ISSN: 0973-1482 EISSN: 1998-4138
Vol. 7, Num. 3, 2011, pp. 336-338

Journal of Cancer Research and Therapeutics, Vol. 7, No. 3, July-September, 2011, pp. 336-338

Letter to the Editor - Documenting a Case

Malignant melanoma with osteoclast-like giant cells: A report of two cases

Garima Goel, Seema Rao, Nita Khurana

Department of Pathology, Maulana Azad Medical College, New Delhi, India
Correspondence Address: Seema Rao, Department of Pathology, Maulana Azad Medical College, New Delhi - 110 002, India, seemarao1974@yahoo.co.in

Code Number: cr11081

PMID: 22044817

DOI: 10.4103/0973-1482.86998

Sir

Osteoclast-like Giant Cells (OGC) associated with giant cell tumor of bone are rarely seen in malignant tumors such as lung cancer, breast cancer, renal cell carcinoma, hepatocellular carcinoma, ovarian cancer, leiomyosarcoma, osteosarcoma, and Malignant Fibrous Histiocytoma (MFH). [1],[2],[3],[4],[5],[6] The presence of OGCs in malignant melanoma has rarely been reported in the literature and may cause misdiagnosis as a histiocytic tumor. Here, we describe two cases of malignant melanoma with presence of OGC.

A 40-year-old male presented with a mass arising from the right nasal cavity since 3 months. Peroperatively, a black coloured soft tissue mass was identified attached to the nasal septum, part of nasal wall, and extending up to the ethmoid sinus and roof of nasal cavity.

Gross examination revealed multiple grey white to dark brown soft tissue bits together measuring 4 × 3 × 2 cm. Cut section of all bits was dark brown. On microscopy, a high-grade malignant tumor comprising plump pleomorphic cells with round to oval nucleus, prominent nucleolus, some multinucleate tumor giant cells, and brisk mitoses was seen. Brown-black melanin pigment was seen in the cytoplasm of many of the tumor cells [Figure - 1]a. Few scattered OGCs were seen interspersed with the malignant tumor cells [Figure - 1]b. On Immunohistochemistry (IHC), the tumor cells were positive for vimentin, Epithelial Membrane Antigen (EMA), and Human Melanoma Black 45 HMB-45, whereas the OGCs were positive for CD68 and negative for HMB45. A follow-up was available for a period of 2 months after the surgery, and the patient was doing well.

A 50-year-old man presented with a gradually increasing spherical swelling on right foot near the dorsal aspect of great toe since 2 years. The swelling was mobile and was associated with pain.

Gross examination revealed three irregular grey-white soft tissue bits together measuring 3.5 × 2 × 1 cm. The histological examination showed a tumor composed of large pleomorphic cells showing intracytoplasmic melanin pigment, large nucleus with prominent nucleoli. Amidst the tumor cells, scattered multinucleate tumor giant cells and OGCs were observed. On IHC, the malignant cell and tumor giant cells were positive for HMB-45 [Figure - 2]a and vimentin, whereas OGCs were positive for CD68 [Figure - 2]b and negative for HMB-45 and vimentin. A follow-up was available for a period of 2 months after the surgery, and the patient was doing well.

Benign multinucleated giant cells have been reported in various neoplasms. However, to the best of our knowledge, only six cases of malignant melanoma associated with OGCs have been reported in literature so far. These giant cells have been termed as OGCs because of their morphological similarity to the cells seen in giant cell tumor of the bone. There has been a lot of discussion about the origin of these cells. One of the theory suggests that they represent transformed tumor cells, whereas the other theory suggests that these cells are reactive histiocytes rather than neoplastic. [2],[3] Various studies, with the help of IHC and ultrastructural studies, have established that these giant cells are derived from monocyte/macrophage lineage and express several such markers, including Leukocyte Common Antigen (LCA) and CD68. [4],[5] OGC formation may be related to cytokine production by the tumor cells as neoplastic cells secrete differentiation factors including Monocyte Chemotactic Protein-1 (MCP1), Osteoclast differentiation factor (ODF), and macrophage-colony stimulating factor (M-CSF), which stimulate the migration of blood monocytes into tumor tissue and enhance their fusion into OGCs. [6] Presence of OGCs in malignant melanoma is a rarity. Daroca et al. reported a case of amelanotic melanoma with the presence of OGCs and suggested that OGCs represent an unusual host response to a dedifferentiated melanoma. [5] In the present study, both cases showed OGCs, which were positive for CD68 and negative for HMB-45.

The histologic appearance of OGC-rich malignant melanoma may cause difficulties in diagnosis. A deep-seated tumor may raise the possibility of a giant cell-rich lesion of the bone involving the soft tissue. However, the absence of an osseous defect on radiological examination along with the absence of osteoid helps in diagnosing the lesion. [5] Malignant melanoma associated with OGCs can also be misdiagnosed as Malignant Fibrous Histiocytoma (MFH) or atypical fibroxanthoma. In such cases, IHC is helpful in distinguishing melanoma from other fibrohistiocytic tumors, the melanoma cells expressing HMB-45. [4]

The prognostic importance of presence of OGCs in malignant tumors remains controversial. A favorable prognosis has been reported in a case of pancreatic cystadenocarcinoma and gastric carcinoma. [7],[8] While in a series of nine cases of pancreatic tumors associated with OGCs, an aggressive behavior was reported. [9] In the few case reports of melanomas with OGCs, an aggressive behavior has been suggested. [6] However, more studies are needed to study its exact implication and long-term prognosis. In the present study, a follow-up was available only for a period of 2 months after the surgery and both patients were doing well.

The OGCs are reactive histiocytic cells produced by host response to tumor cells and express the monocyte/macrophage markers such as CD68 and are negative for melanoma markers such as HMB-45. The awareness of this entity is important to avoid any misdiagnosis as primary histiocytic neoplasm or a giant cell-rich lesion of the bone, especially in cases of amelanotic melanoma and spindle cell variant of melanoma.

References

1.Sarma DP, Santos EE, Wang B. Leiomyosarcoma of the skin with osteoclast-like giant cells: A case report. J Med Case Reports 2007;1:180.  Back to cited text no. 1  [PUBMED]  [FULLTEXT]
2.Leury KM, Wong S, Chow TC. A malignant stromal tumor with osteoclast-like giant cells. Arch Pathol Lab Med 2002;126:972-4.  Back to cited text no. 2    
3.Terada T, Endo K, Maeta H. Epithelioid leiomyosarcoma with osteoclast-like giant cell in the rectum. Arch Pathol Lab Med 2000;124:438-40.  Back to cited text no. 3    
4.Denton KI, Stretch J, Anthansou N. Osteoclast-like giant cells in malignant melanoma. Histopathology 1993;20:179-81.  Back to cited text no. 4    
5.Daroca PJ, Reed R, Martin P. Metastatic amelanotic melanoma simulating giant-cell tumor of bone. Hum Pathol 1990;21:978-80.  Back to cited text no. 5    
6.Nabeel AB, Samih S. Malignant melanoma with osteoclast-like giant cells: An Unusual host response: Immunohistochemical and ultrastructural study of three cases and literature. Am J Dermatopathol 2005;27:126-9.   Back to cited text no. 6    
7. Suda K, Takase M, Oyama T. An osteoclast-like giant cell tumor pattern in a mucinous cystadenocarcinoma of the pancreas with lymph node metastasis in a patient surviving over 10 years. Virchows Arch 2001;438:519-20.   Back to cited text no. 7    
8. Zheng LD, Yang XP, Pan HX, Nie X, Jun HE, Qing LV, et al. Gastric carcinoma with osteoclast-like giant cells: A case report and review of the literature. J Zhejiang Univ Sci B 2009;10:237-41.  Back to cited text no. 8    
9.Molberg KH, Heffess C, Delgado R. Undifferentiated carcinoma with osteoclast-like giant cells of the pancreas and periampullary region. Cancer 1998;82:1279-87.  Back to cited text no. 9    

Copyright 2011 - Journal of Cancer Research and Therapeutics  


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