|Year : 2013 | Volume
| Issue : 4 | Page : 706-708
Balloon cell melanoma of the anal canal: A wolf in sheep's clothing?
Munita Meenu Bal, Mukta Ramadwar, Kedar Deodhar
Department of Pathology, Tata Memorial Hospital, Mumbai, India
|Date of Web Publication||11-Feb-2014|
Munita Meenu Bal
Department of Pathology, Tata Memorial Hospital, Parel, Mumbai 400 012
Source of Support: None, Conflict of Interest: None
Balloon cell melanoma (BCM) is a rare histologic variant of cutaneous malignant melanoma with exceptional reports of occurrences at non-cutaneous sites. Herein we present a case of primary amelanotic BCM of anal canal, a heretofore undescribed location. Histologically, the tumor was characterized by sheets of pale cells that bore striking resemblance to foamy macrophages. Presence of rare atypical mitoses confirmed the malignant nature of the cells. Neoplastic cells were immunoreactive for S100, Melan-A, and focally for HMB-45 while were negative for myogenic, gastrointestinal stromal tumor, epithelial and neuroendocrine markers. Resemblance to foamy macrophages, bland cytology and absence of pigment imparts this tumor a deceptively benign histological appearance making it prone to diagnostic pitfalls. Awareness of this rare entity and judicious employment of immunohistochemistry is imperative in segregating it from its diverse mimics.
Keywords: Anal canal, balloon cell melanoma, differential diagnosis, immunohistochemistry
|How to cite this article:|
Bal MM, Ramadwar M, Deodhar K. Balloon cell melanoma of the anal canal: A wolf in sheep's clothing?. J Can Res Ther 2013;9:706-8
| > Introduction|| |
Balloon cell melanoma (BCM) is a very rare, albeit, well established histologic variant of malignant melanoma. Most of the cases described in literature are cutaneous in origin;  exceptionally rare non-cutaneous occurrences of primary BCM in brain  and choroid  have been documented. Herein, we report a case of anorectal BCM, a hitherto unreported site. We describe this case not only for its rarity but also for the considerable dilemma entailed in reaching the diagnosis.
| > Case Report|| |
A 73-year-old man, chronic smoker, presented with a bleeding per rectum. Except for a mild pallor, general physical examination was within normal limits. On proctoscopy, a 3 cm infiltrative polypoid mass involving 1/3 rd of the luminal circumference was seen 5 cm from the anal verge. Perianal skin was unremarkable. Investigations yielded low hemoglobin of 12.6 g/dL (13.0-17.0 g/dL) and platelet count of 113 × 10 6 /L (150-400 × 10 6 /L). White blood cell count was within normal limits. Serum carcinoembryonic antigen level was 3.28 ng/ml (0.3-2.7 ng/ml) and uric acid was 7.5 mg/dl (3.5-7.2 mg/dl). Remaining investigations were within normal limits. Metastatic work-up was negative. A biopsy was performed.
Biopsy revealed ulcerated mucosa with sheets of large sized clear cells underneath. These were admixed with occasional non-clear epithelioid tumor cells. A few mitoses, including scant atypical one, were identified. Mucicarmine stain for intracytoplasmic mucin was negative. Immunohistochemistry (IHC) for cytokeratin (CK), epithelial membrane antigen (EMA), synaptophysin, chromogranin, smooth muscle actin (SMA), desmin, CD117 and HMB-45 was negative. The nature of clear cells was difficult to ascertain and were assumed to be macrophages accompanying the scant non-clear epithelioid neoplastic cells. However, due to presence of an occasional atypical mitosis, a diagnosis of 'malignant tumor, cannot characterize further' was offered. A transanal excision was performed.
On macroscopic examination, a 3 × 2.5 cm ulcerative, polypoid growth involving 1/3 rd of the luminal circumference was identified. Tumor thickness was 0.5 cm. Microscopy revealed an ulcerated, polypoid tumor infiltrating anorectal mucosa. Tumor was dominantly composed of a large central 'white' spheroid island populated by sheets of large-sized cells with abundant clear to finely vacuolated cytoplasm [Figure 1]. The cells possessed central to eccentric, mildly hyperchromatic nuclei and inconspicuous nucleoli. Variable sized vessels traversed the sheets of pale cells; their muscular coats notably lacked radiating epithelioid or spindle cells. At the periphery, an attenuated brim of non-clear epithelioid neoplastic cells arranged in nests was seen intermixed with the clear cells [Figure 1]. These epithelioid cells possessed moderate amounts of cytoplasm and prominent nucleoli. No pigment or pagetoid spread was discernible. On IHC, clear and non-clear tumor cells were uniformly positive for Melan-A and S100. Focal positivity for HMB-45 was identified in the peripheral non-clear tumor cells [Figure 2]. Neoplastic cells did not express CK, EMA, synaptophysin, chromogranin, SMA, desmin, CD117 and CD68. A diagnosis of primary anal amelanotic BCM was made. No emboli or perineural infiltration was seen. Resection margins were free of tumor. The patient remained disease free for 6 months following which he developed local recurrence.
|Figure 1: Balloon cell melanoma, H and E; (a) Scanner revealed a pale 'white' tumor composed of sheets of balloon cells underneath rectal mucosa (original magnification, ×20); (b) Balloon cells reminiscent of foam cells (original magnification, ×100); (c) Epithelioid non-balloon melanoma cells at the periphery (original magnification, ×100); (d) High power view of balloon cells exhibiting bland cytology and empty-looking cytoplasm (original magnification, ×400)|
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|Figure 2: Immunoreactivity of balloon cell melanoma; (a) Balloon cells expressed Melan A (original magnification, ×20); (b) Strong cytoplasmic and nuclear expression for S100 (original magnification ×20); (c) HMB 45 expression was restricted to the non-balloon tumor cells (original magnification, ×20)|
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| > Discussion|| |
BCM is an extremely rare form of malignant melanoma characterized by proliferation of balloon cells. The first case of BCM was reported in 1970 by Gardner.  Nearly all BCM cases are cutaneous in origin with exceptional occurrences at non-cutaneous sites. , To the best of our knowledge, this case is the first report of BCM arising in the anal canal. This case underscores the need to be aware of this rare variant of melanoma that can project a misleadingly bland appearance and masquerade as diverse pathological entities.
BCM is characterized by presence of eponymous balloon cells; their close semblance to foam cells projects an alarmingly deceptive facade that belies their malignant nature. Further, ano-rectal location and lack of pigment can be misleading for an unsuspecting pathologist. In a small biopsy that is entirely composed of balloon cells, the latter could be easily mistaken for foamy macrophages and disregarded leading to a repeat biopsy. On the other hand, erroneous interpretation of clear cells in rectal biopsy as signet ring cells swollen with mucin can be a trapdoor, more often when epithelioid cells are also intermixed. Perivascular epithelioid cell tumor (PEComa) and clear cell sarcoma (CCS) are other close impersonators of BCM on account of clear cell morphology and melanocytic differentiation. Other uncommon mimics include tumors that infrequently display a clear cell phenotype such as myoepithelial carcinoma, neuroendocrine tumor (NET), gastrointestinal stromal tumor (GIST), epithelioid leiomyomatous tumor, sebaceous carcinoma and liposarcoma. Metastatic clear cell tumors of renal or adrenal origin as differential diagnoses may entirely derail the focus of diagnostic work-up. Owing to their resemblance to macrophages, many uncommon non-neoplastic lesions may also trickle into the picture, such as a xanthoma, Rosai-Dorfman disease, leprosy, atypical mycobacterial infections or Whipple's disease. This list of disparate differential diagnoses encompassing infective etiologies, benign lesions, carcinomas, sarcomas and metastatic tumors, itself reflects the vastly divergent tracks a pathologist may undertake, employing innumerable immunohistochemical antibodies.
The balloon cells in BCM do not contain mucin; glycogen or lipid is variable; while a few demonstrate staining for Masson's Fontana.  BCM shows immunoreactivity for most of the melanocytic markers, S100 protein, HMB-45, Melan-A, microphthalmia-transcription-factor, tyrosinase. Reactivity may be focal or variable which may wrongly impact biopsy diagnosis if only one melanocytic marker is employed. BCM is negative for CK, CD117, SMA, desmin, synaptophysin, chromogranin and CD68. Although, indistinguishable on histology and IHC, CCS can be segregated clinically as it arises in soft tissues unlike melanoma that occurs in cutaneous or mucosal sites. Moreover, melanoma and CCS are distinct entities genetically; latter being characterized by translocation t (12;22) (q13;q12).  PEComas also bear striking similitude to BCM. However, vessels with tumor cells emanating from the vascular muscle coat are a morphological clue in PEComa whereas structurally normal vessels are present as bystanders in BCM. PEComas are immunoreactive for smooth muscle markers (SMA and desmin) in addition to melanocytic markers. Unlike BCM, carcinomas are immunoreactive for keratins and EMA; rectal adenocarcinoma for CK20 and CDX2; NETs for neuroendocrine markers, synaptophysin, chromogranin, PGP 9.5 and CD56; GIST for c-kit, DOG1 and/or PDGFRA; and leiomyomatous neoplasms for desmin, SMA and h-caldesmon.
Prognosis, treatment and outcome of BCM is comparable to conventional melanoma; 5-year survival rate is less than 20%.  BCM is a morphologically deceptive variant of melanoma that may arise at non-cutaneous sites. On one hand, BCM cells can resemble innocuous foamy macrophages, while on the other bear semblance to innumerable clear cell tumors of gastrointestinal tract. Awareness of this entity and prudent use of IHC is imperative in avoiding grave diagnostic pitfalls.
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[Figure 1], [Figure 2]