|Year : 2014 | Volume
| Issue : 1 | Page : 197-199
Impact of hypothyroidism on primary anal malignant melanoma: A rare entity
Siddharth Singh, Satyajeet Verma, Sanjay Kala
Department of Surgery, G.S.V.M. Medical College, Kanpur, Uttar Pradesh, India
|Date of Web Publication||23-Apr-2014|
Department of Surgery, G.S.V.M. Medical College, Kanpur - 208 002, Uttar Pradesh
Source of Support: None, Conflict of Interest: None
Primary melanoma of the anal canal is rare and highly malignant condition, which is 1% of all invasive tumors in this site. This condition is often mistaken for benign conditions as either hemorrhoids or rectal polyp. Thyroid-stimulating hormone stimulation causes high proliferation of malignant melanoma. The association of hypothyroidism with primary malignant melanoma of anal canal is very rare. We are reporting such a very rare case.
Keywords: Hypothyroidism, malignant melanoma, thyroid-stimulating hormone
|How to cite this article:|
Singh S, Verma S, Kala S. Impact of hypothyroidism on primary anal malignant melanoma: A rare entity. J Can Res Ther 2014;10:197-9
| > Introduction|| |
Primary anal malignant melanoma is highly malignant, but rare disease. This disease is often mistaken for benign conditions, i.e., hemorrhoids or rectal polyp as they are the most common cause of anorectal bleeding. 
Ellerhorst et al. reported prevalence of hypothyroidism among melanoma patients that exceed the prevalence in the general population. In this cohort of hypothyroid melanoma patients, the diagnosis of hypothyroidism preceded or was made concurrently with the diagnosis of melanoma in the majority of cases.  We are reporting a very rare case of primary anal melanoma with hypothyroidism.
| > Case report|| |
A 54-year-old male presented to us with complaints of episodes of bleeding per rectum, pain and difficulty in defecation for last 1 year. He is known case of hypothyroidism for last 6 years, which was diagnosed for cold intolerance, obesity and excessive fatigability. He had been taking 100 μg of tablet thyroxine irregularly for first 3 months then went non-compliant. On general examination, patient had severe pallor. Rest of the general and systemic examination revealed no significant abnormalities.
DigitalRactalExamination (DRE) displayed irregular circumferential growth starting just inside the anal verge. Upper limit could not be negotiated due to narrowing of the lumen by growth. There was bleeding on touch.
Blood chemistry revealed hemoglobin-6 mg%. Serum protein was 4.5 gm%. Liver and Renal function tests were within normal limits. Enzyme-linked immunosorbent assay for human immunodeficiency virus, Australia antigen were negative.
Thyroid function test revealed hypothyroid status, i.e., T3 free-1.82 pg/ml (2.30-4.20), T4 free-0.38 ng/dl (0.89-1.76), thyroid-stimulating hormone (TSH) 133.1 uIU/ml (90.350-5.500). Contrast enhanced computed tomography abdomen revealed narrowing of lower rectal region and growth at lower recto-anal region without any lymphadenopathy, ascites and hepatomegaly [Figure 1]. Pre-operative incisional biopsy revealed malignant melanoma.
|Figure 1: Contrast enhanced computed tomography scan-abdomen revealed rectal growth|
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Patient was admitted and transfused 4 units of whole blood. After improvement form anemia and achieving euthyroid status by tittering with doses of thyroxin, abdominoperineal resection was planned and executed [Figure 2].
Post-operative period was uneventful. After 4 weeks, post-operatively, patient was doing fine with a normally functioning end colostomy.
Histopathology report revealed malignant melanoma of the anal canal. Tumor has invaded the serosa. Proximal resected margin free from tumor involvement. There were no regional lymph node metastases. Immunohistochemistry analysis revealed TSH-receptor positive melanoma cells with intense immunoactivity [Figure 3]. The patient had been kept under close follow-up for 1 year after which he was lost in follow-up.
|Figure 3: Expression of thyroid-stimulating hormone-receptor positive melanoma cells showing immuno activity|
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| > Discussion|| |
Malignant melanoma of the anorectal region is extremely rare and virulent tumor. Moore was the first person to report it in 1857. Primary anorectal melanoma comprises 0.25-1.25% of all the malignancies originating in this anatomic region.  Of all melanomas, anal melanoma represents 0.4-1.6% and is the third most common site of origin, following the skin and eye. It is usually a disease of old age, affecting mostly the fifth to seventh decade of life. There is no sex predilection, but cases in whites outnumber blacks. ,
Surgical therapy in the management of anal melanoma is uncertain and controversial, but depends upon the clinical stage of the disease. Procedures include a conservative approach of wide local excision and a more radical approach of Abdomino-perinealResection (APR).  However, the rarity of this tumor, advanced stage at presentation and poor prognosis have confounded attempts to clarify optimal surgical intervention. Local lesions (without palpable lymph nodes) are treated by APR with or without groin dissection, whereas in an advanced disease with distant metastases and large primary, palliative treatment (local segmental resection, colostomy in intestinal obstruction) along with chemo-radiation may be done. , A limited number of chemotherapeutic agents have shown effectiveness in metastatic cutaneous melanoma. 
Despite the dismal prognosis of melanomas, there are a few isolated reports of lengthy survival.  The factors predictive of prolonged survival in these unusual cases are unknown, but may be correlated with the depth of tumor invasion or with the absence of distant metastases at the time of diagnosis. , In operable cases of anal melanomas where APR was the primary modality of treatment, 5 years survival up to 29% reported. 
TSH-receptors are expressed by melanoma cells which are functional and induced to proliferate at a physiologically relevant concentration of TSH.  Ellerhorst et al. reported that all types of lesions of melanocytic origin, benign or malignant, express Thyroid Stimulating Hormone-Receptor (TSHR), and that receptor expression is increased in melanomas, potentially rendering them more sensitive to TSH. Furthermore, it is demonstrated that cultured melanoma cells produce cAdenosine Mono Phosphate and activate the mitogen-activated protein kinase pathway in response to TSH, indicating that the receptor is functional. Finally, it shows that TSH induces proliferation of melanoma cells, but not melanocytes, providing direct evidence for TSH as a melanoma growth factor. 
Our patient had hypothyroidism for last 6 years. Raised TSH level might have caused increased growth of the malignant melanoma.
Finding like TSH as a novel growth factor for human melanoma open the entirely unexplored field of melanoma regulation by metabolic hormones and provide the opportunity for numerous, unique interventions that may be effective in the management and prevention of this disease. 
The purpose of presenting this case is also to add that in all kind of cutaneous and non-cutaneous melanoma, thyroid profile must be explored although further studies are required to define this association of non-cutaneous malignant melanoma and hypothyroidism.
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[Figure 1], [Figure 2], [Figure 3]