Case 4 -

Metastatic Malignant Melanoma Savitri Krishnamurthy MD Anderson Cancer Center Houston, TX

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Clinical History An 85 year old gentleman with chief complaints of left sided chest pain and breathlessness of gradual onset. In addition, he also gave the history of weight loss (17lb), anorexia and dyschezia. He had been a 50 pack a year cigarette smoker in the past. He underwent carolid endarterectomy, hernia repair, and removal of small skin lesions in the past. Chest X-ray revealed a right lower lobe lung mass measuring 3.0cm in maximum dimension. Subsequently, CT scan showed in addition a 2.5cm right adrenal mass. The patient was referred for further evaluation of the lung and adrenal mass. Fine needle aspiration (FNA) of the adrenal mass was performed. Direct smears of FNA of the adrenal mass are provided. Case 4 - Figure 1 Case 4 - Figure 2 Case 4 - Figure 3 Case 4 - Figure 4 Case 4 - Figure 5 Case 4 - Figure 6 Case 4 - Figure 7 Case 4 - Figure 8 Case 4 - Figure 9 The tumor cells are negative for pancytokeratin. The adrenal cortical cells interspersed amidst the tumor cells in the tissue section show positive staining. Case 4 - Figure 10 The tumor cells are uniformly and strongly positive for Melan A(A103) and demonstrate the characteristic coarse and granular cytoplasmic positivity for this marker. Case 4 - Figure 11 S-100 immunostain shows rare positively stained tumor cells. Case 4 - Figure 12 The tumor cells are negative for inhibin. Case 4 - Figure 13 The S-100 immunostain performed on the cell block shows diffuse positivity in almost all of the tumor cells. Pathological/Microscopic Findings and any Immunohistochemical or Other Studies: Direct smears of FNA of the right adrenal gland demonstrates increased cellularity with many single as well as loose clusters and small sheets of tumor cells. Individual tumor cells exhibit scant to moderate amounts of cytoplasm and a centrally placed small or large sized nucleolus. Some of the tumor cells are elongated with similar nuclear features. Mitotic figures are noted in many tumor cells. Many apoptotic bodies are also noted amidst the tumor cells. There is no evidence of necrosis in the direct smears or tissue section of the core needle biopsy. Differential Diagnoses: 1. Metastatic Non-small cell lung carcinoma. 2. Primary non-functional Adrenal cortical carcinoma. 3. Metastatic melanoma Final Diagnosis: Metastatic Malignant Melanoma Case Discussion: The clinical presentation of the patient with a lung and adrenal mass raises several possibities regarding the etiology of the mass in the adrenal gland. Either the adrenal gland or lung may be the primary source of the tumor. Alternately, the tumor in both sites may be metastatic and not necessarily the primary site of origin of the tumor. The cytomorphological features of the tumor cells with the presence of a centrally placed nucleus, a small or prominent nucleolus and scant to moderate amounts of cytoplasm is unlike that of an Adrenal cortical carcinoma. The tumor cells in the latter tumors generally recapitulate the normal adrenal gland with eosinophilic or bubbly clear cytoplasm with an often eccentrically placed nucleus. Nuclear atypia in these tumors varies from nonexistant to highly pleomorphic forms. The presence of necrosis and increased mitotic activity is usually observed in these tumors. The cytologic features of the tumor cells, is more in keeping with a metastatic non- small cell lung carcinoma. Immunostaining revealed the tumor cells to be negative for pancytokeratin which excludes metastasis from lung primary. Amongst the three adrenal cortical markers including calretinin, Melan A and inhibin, the tumor cells were positive only for Melan A (A103) with the characteristic coarse and granular cytoplasmic staining. Adrenal cortical carcinomas are generally positive for all the three markers. In addition to Melan A, the tumor cells were positive for S100 which is useful for the distinction of adrenal cortical carcinomas from melanoma. The tumor cells were negative for HMB45. The overall cytomorphologic features of the tumor with the presence of spindle and epithelioid tumor cells negative for pancytokeratin and positive for S-100 and Melan A is consistent with metastatic melanoma. The history of resection of malignant melanoma of right ear lobe 8 years prior to the current biopsy was elicited after establishment of the final diagnosis of the right adrenal mass. Review of the Literature/Treatment Options: Metastatic tumors involving adrenal gland are more common than primary tumors. The adrenal gland is the fourth most frequent site of metastasis after lungs, liver, and bone. The most common primary sites include lungs, stomach, esophagus, and liver/bile duct. The incidence of melanoma metastasis to the adrenal gland is not very well established. In the series published from MD Anderson Cancer Center, they were reported in 13% of the patients with melanoma. Patients with melanoma adrenal metastasis have a poor prognosis. Melanoma cells express high affinity glucocorticoid receptors and adrenalectomy for melanoma metastasis provides good palliation of symptoms and is associated with prolonged survival in a selected cohort of patients. For patients with metastatic melanoma, the cytotoxic agent Dacarbazine is approved by the food and drug administration (FDA) for treatment. The overall response rate is however only 15-20%. Conclusion(s): This case illustrates the value of a detailed clinical history, recognition of pertinent cytomorphological features and ancilary immunostaining in rendering an accurate preoperative diagnosis. Take Home Message/Key points Melanoma can demonstrate varied cytomorphological features. The present case exhibits features that overlap with poorly differentiated, Non- small cell carcinoma. The cytologic features useful to consider melanoma in the differential diagnosis includes the presence of distinctly epithelioid cells together, with elongated cells exhibiting cytoplasmic processes. Melanoma marker A103 can be positive in both melanoma and Adrenal cortical carcinoma. Immunostains useful for the distinction are S-100, HMB-45, tyrosinase for the former and calretinin and inhibin for the latter. Metastatic tumors involving adrenal gland are more common than primary tumors. The adrenal is the fourth most frequent site of spread of tumors after lungs, liver, and bone. References: Lam Ky and Lo Cy: Metastatic tumors of the adrenal glands: A 30 year experience in a teaching hospital. Clinical Endocrinology; 56, 95-101, 2002. Mittendorf EA, Lim SJ, Schacherer CW et al. Melanoma adrenal metastasis: natural history and surgical management. The Am Journal of Surgery: 195, 363-369, 2008. Zhang PJ, Genega EM, Tomaszewski JE, et al: The role of calretinin inhibin, melan A, BCL-2 and c-kit in differentiating adrenal cortical and medullary tumors: an immunohistochemical study. Mod Pathol; 16:591-597, 2003. DeLellis RA, Lloyd RV, Heitz PU, Eng C Secondary tumors, Tumors of the adrenal gland. WHO classification of tumors, Pathology and Genetics, Tumors of Endocrine Organs, IARC Press, 2004.