Heterogeneity of PD-L1 expression and CD8 tumor-infiltrating lymphocytes among subtypes of cutaneous adnexal carcinomas.

BACKGROUND: Adnexal carcinomas are rare and heterogeneous skin tumors, for which no standard treatments exist for locally advanced or metastatic tumors. AIM OF THE STUDY: To evaluate the expression of PD-L1 and CD8 in adnexal carcinomas, and to study the association between PD-L1 expression, intra-tumoral T cell CD8+ infiltrate, and metastatic evolution. MATERIALS AND METHODS: Eighty-three adnexal carcinomas were included. Immunohistochemistry using anti-PD-L1 monoclonal antibodies (E1L3N and 22C3) and CD8 was performed. PD-L1 expression in tumor and immune cells, and CD8+ tumor-infiltrating lymphocyte (TIL) density were analyzed semi-quantitatively. RESULTS: Among the 60 sweat gland, 18 sebaceous and 5 trichoblastic carcinomas, 11% expressed PD-L1 in ≥ 1% tumor cells, more frequently sweat gland carcinomas (13%, 8/60) including apocrine carcinoma (40%, 2/5) and invasive extramammary Paget disease (57%, 4/7). Immune cells expressed significantly more PD-L1 than tumor cells (p < 0.01). Dense CD8+ TILs were present in 60% trichoblastic, 43% sweat gland, and 39% sebaceous carcinomas. CD8+ TILs were associated with PD-L1 expression by tumor cells (p < 0.01). Thirteen patients out of 47 developed metastases (27%) with a median follow-up of 30.5 months (range 7-36). Expression of PD-L1 by tumor cells was associated with the development of metastasis in univariate analysis (HR 4.0, 95% CI 1.1-15, p = 0.0377) but not in multivariate analysis (HR 4.1, 95% CI 0.6-29, p = 0.15). CONCLUSION: PD-L1 expression is highly heterogeneous among adnexal carcinoma subtypes, higher in apocrine carcinoma and invasive extramammary Paget disease, and associated with CD8+ TILs. Our data suggest the interest of evaluating anti-PD1 immunotherapy in advanced or metastatic cutaneous adnexal carcinoma.

Significant association between TNFAIP3 inactivation and biased immunoglobulin heavy chain variable region 4-34 usage in mucosa-associated lymphoid tissue lymphoma.

Both antigenic drive and genetic change play critical roles in the development of mucosa-associated lymphoid tissue (MALT) lymphoma, but neither alone is sufficient for malignant transformation, and lymphoma development critically depends on their cooperation. However, which of these different events concur and how they cooperate in MALT lymphomagenesis is totally unknown. To explore this, we investigated somatic mutations of 17 genes and immunoglobulin heavy chain variable region (IGHV) usage in 179 MALT lymphomas from various sites. We showed that: (1) there was a significant association between the biased usage of IGHV4-34 (binds to the carbohydrate I/i antigens) and inactivating mutation of TNFAIP3 [encoding a global negative regulator of the canonical nuclear factor-κB (NF-κB) pathway] in ocular adnexal MALT lymphoma; (2) IGHV1-69 was significantly overrepresented (54%) in MALT lymphoma of the salivary gland, but was not associated with mutation in any of the 17 genes investigated; and (3) MALT lymphoma lacked mutations that are frequently seen in other B-cell lymphomas characterized by constitutive NF-κB activities, including mutations in CD79B, CARD11, MYD88, TNFRSF11A, and TRAF3. Our findings show, for the first time, a significant association between biased usage of autoreactive IGHV and somatic mutation of NF-κB regulators in MALT lymphoma, arguing for their cooperation in sustaining chronic B-cell receptor signalling and driving oncogenesis in lymphoma development. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Extranodal marginal zone lymphoma from ocular adnexae with subcutaneous involvement.

Extranodal marginal zone lymphoma (MZL) of mucosa-associated lymphoid tissue usually originates from cutaneous or mucosal surfaces. A rare site of involvement is the subcutaneous tissue of any location. Here, we describe a 58-year-old man who presented with bilateral extranodal MZL of mucosa-associated lymphoid tissue from ocular adnexae that involved subcutaneous tissue and subsequently extended to multiple anatomical locations in the head and neck, upper back, and arm. The neoplastic cells expressed B-cell markers, and the plasma cells expressed IgG4. The unusual pattern of infiltration of this extranodal MZL and the possible significance of IgG4 expression in this case are discussed.

Eruptive vellus hair cysts: report of a new case with immunohistochemical study and literature review.

Eruptive vellus hair cysts (EVHC) are rather uncommon lesions, of which 222 cases have been published in the literature. Their etiopathogenesis is poorly known. We report herein a new typical case of EVHC that was studied immunohistochemically. A 15-year-old male presented with a 4-year history of progressively developing small brown-gray papules on the trunk and extremities. Microscopically the lesions consisted of small epidermoid cysts containing vellus hairs. Immunohistochemically, the lesions expressed keratin 1/10, calretinin and p63 but no epithelial membrane antigen, filaggrin or androgen receptors. A review of the relevant literature shows that EVHC may be inherited or acquired and may be associated to other genodermatoses, namely sebocystomatosis. They could be due to hamartomatous follicular growth, to a trouble in infundibular keratinization leading to vellus hair follicle occlusion, or represent an example of acquired hamartoma. Although benign, this condition is difficult to treat.