Expression of TdT in Merkel Cell Carcinoma and Small Cell Lung Carcinoma

Abstract

Merkel cell carcinoma (MCC) is an uncommon tumor with indistinct clinical features. The differential diagnosis includes small cell lung carcinoma (SCLC). We characterized the expression of terminal deoxynucleotidyl transferase (TdT) and a panel of immunohistochemical markers in 40 MCC, 30 SCLC, and 6 pulmonary carcinoid tumor (PCT) cases. We used antibodies against TdT, thyroid transcription factor (TTF)-1, cytokeratins (CKs) 7 and 20, chromogranin, and synaptophysin. Immunostaining was recorded semiquantitatively. Of 40 MCC cases, 28 (70%) were positive for TdT, showing, on average, more than 25% of tumor cells reactive with moderate nuclear staining intensity. TTF-1 (1 [3%]), CK7 (2 [5%]), CK20 (35 [88%]), chromogranin (29 [73%]), and synaptophysin (39 [98%]) were expressed in the MCCs. Of the 5 CK20- MCC cases, 4 were positive for TdT. SCLC showed expression of TTF-1 (23/30 [77%]), CK7 (22/30 [73%]), chromogranin (16/30 [53%]), and synaptophysin (22 [73%]) and no CK20 (0%) expression. Of 30 SCLC cases, 2 (7%) were positive for TdT. TdT may be beneficial in rare cases of CK20- MCC and may assist in distinguishing between MCC and SCLC. There is significant immunohistochemical variability and overlap between these 2 tumors.

Early B-Cell Differentiation in Merkel Cell Carcinomas: Clues to Cellular Ancestry

“…Identifying pro/pre-or pre-B cells as the cellular ancestors of MCCs is also expected to impact current treatment regimens of MCCs, which is of major significance in the context of the very poor prognosis for patients with MCCs after primary MCC diagnosis. Next to this, it might also influence the current understanding of the cellular ancestry of other neuroendocrine cancers such as small cell lung cancer in which to a lesser extent TdT and PAX5 expression has been observed (18,19).…”

“…In the past years, evidence is accumulating that MCCs express early B-cell lineage markers (15)(16)(17)(18)(19)(20)(21)(22). For example, specific expression of terminal deoxynucleotidyl transferase (TdT) as assessed by immunohistochemistry, which normally is restricted to thymocytes and precursors of lymphocytes in the bone marrow, has been reported in 72.5% (95 of 131) of MCCs (15)(16)(17)(18)(19).…”

“…For example, specific expression of terminal deoxynucleotidyl transferase (TdT) as assessed by immunohistochemistry, which normally is restricted to thymocytes and precursors of lymphocytes in the bone marrow, has been reported in 72.5% (95 of 131) of MCCs (15)(16)(17)(18)(19). In addition, a number of studies have reported immunostaining of the B-cell-specific activating protein (BSAP; syn: PAX5) in 83.6% (102 of 122) of MCCs (16,(19)(20)(21)(22).…”

Merkel cell carcinoma of lymph node with unknown primary has a significantly lower association with Merkel cell polyomavirus than its cutaneous counterpart

“…Eventually 763 cases of cutaneous Merkel cell carcinoma were retrieved from the English literature and included in our review. 15,[18][19][20][21][22][23][24][25][26][27][28][29] …”

“…We also studied expression of PAX5 and TdT in our cases; both markers have been detected in the majority of cutaneous Merkel cell carcinomas. [18][19][20][21][22] …”