The relationship of melanocytic differentiation with prognostic markers in medullary thyroid carcinomas

Medullary thyroid carcinoma (MTC) makes up 5-10% of thyroid malignancies. Small cell, squamous, giant cell or melanocytic differentiation can rarely be seen in MTCs. It is important to determine those with the potential to act aggressively such as cases with melanocytic differentiation at the time of diagnosis.

A total of 46 MTC cases diagnosed at four different centers between 2002 and 2013 were included in the study. Immunohistochemical (IHC) staining with Melan-A and HMB-45 was performed in all cases.

Six of the 46 MTC cases were medullary microcarcinomas and three were multicentric medullary carcinomas. There were 34 females and 12 males with a mean age at onset of 51.4 years and mean tumor diameter of 23.2mm. Lymph node metastasis (LNM) was found in 13 of the 38 cases that had data regarding the lymph nodes. Immunohistochemically, Melan A staining was seen in four cases. HMB45 staining was seen in four cases. A statistically significant relationship was found between LNM and diameter, Melan A expression (p=0.02, p=0.03 respectively) but there was no significant relationship with HMB45 expression (p=0.07). General survival data were present for 35 of the 46 cases. All cases without lymph node metastasis survived (21/21) while 8 of 11 cases with lymph node metastasis survived among cases with survival data; one case that was diffuse-strong positive for both HMB45 and Melan A was lost due to distant organ metastasis six months after the diagnosis.

Should the possibility of melanocytic differentiation be evaluated in cases where melanocytic differentiation is not reflected in the morphology (lack of pigment) in MTCs? We did not come across a study on the subject in the English literature. The effect of melanocytic differentiation on the prognosis in MTCs should be investigated in larger series.