Melanocytic Skin Neoplasms: What Lesson From Genomic Aberrations? Abstract: Studies on the genomic aberrations in melanocytic neoplasms have shown a complex genomic landscape. In nevi and melanomas, a MAP-kinase pathway activation was generally found, produced by different chromosomal aberrations, including BRAF, NRAS, HRAS, GNAQ, GNA11, BAP1, CTNNB1, MAP2K1, PRKAR1A, and NF1 mutations, and ALK, ROS1, NTRK1, RET, MET, BRAF, NTRK3, and PRKCA fusions. Melanomas also showed a variable number of additional mutations ablating tumor-suppression mechanisms and activating other oncogenic pathways, including CDKN2A loss, PTEN loss, as well as TP53 and TERT-promoter mutations. Moreover, borderline melanocytic tumors displayed the same chromosomal aberrations, but more mutations than nevi and fewer than melanomas. In this context, the notion that melanocytic neoplasms can be classified as benign/malignant is hardly supportable, because all neoplasms harbor a certain number of mutations and the progression risk, that is, the malignant potential, is related and proportional to the burden of pathogenic mutations. Moreover, from the genomic analysis, in parallel to the current diagnostic categories of “nevi,” “melanomas,” and “melanocytomas,” some aggregations or classes of tumors based on the characteristic types of driver mutations/fusions emerge as possible and more rationale, including Spitzoid neoplasms, blue neoplasms, BAP1-inactivated melanocytic neoplasms, deep penetrating melanocytic neoplasms, pigment-synthesizing melanocytic neoplasms, and “common” melanocytic neoplasms. Each of these classes, showing the same driver mutations/fusions, demonstrates to have the same pathogenesis and may be genetically considered as a single tumor, although with a variable amount of progression risk. Histologic features, being an expression of the mutational state, could be used to obtain an approximate risk assessment in each single tumor.

αEβ7 Expression Increases With the Extent of Cutaneous Involvement in Mycosis Fungoides Background: Cell adhesion molecules are essential to lymphocyte migration in neoplastic and inflammatory skin diseases. Our aim was to investigate possible differences in cell adhesion molecule expression between mycosis fungoides (MF) and inflammatory skin diseases (drug reactions and allergic contact dermatitis). Methods: We selected 33 biopsies from patients with MF and 10 biopsies of patients with inflammatory skin diseases from Department of Pathology—Universidade Federal de São Paulo (UNIFESP) from January 1997 to December 2013. Expression of α4β1 integrin and αEβ7 integrin was assessed by immunohistochemistry in intraepidermal lymphocytes by counting 4 microscopic epidermal fields (×400) and comparing those between the 2 groups. Results: We observed increased expression of integrin αEβ7 in intraepidermal lymphocytes in advanced stages of MF (T3 and T4). αEβ7 expression was detected in intraepidermal dendritic cells of MF and inflammatory diseases samples. The expression of E-cadherin in epidermal cells in MF outlined Pautrier microabscesses, whereas in inflammatory diseases, spongiosis reduced its expression in keratinocytes. Conclusions: The findings presented here support the idea that the lymphocyte migratory mechanism observed in neoplasms is similar to that of inflammatory processes of the skin.

Spindle Cell Predominant Trichodiscoma or Spindle Cell Lipoma With Adnexal Induction? A Study of 25 Cases, Revealing a Subset of Cases With RB1 Heterozygous Deletion in the Spindle Cell Stroma Abstract: In our routine and consultative pathology practices, we have noticed that a relatively high proportion of spindle cell predominant trichodiscomas demonstrate a remarkable stromal admixture of adipose tissue, which along with spindle cells, prominent collagen bundles and myxoid change closely resembles spindle cell lipoma (SCL). To clarify their possible relationship to SCL, 25 cases of trichodiscoma and fibrofolliculoma with stromal “lipomatous metaplasia” were collected and examined using immunohistochemical stains [CD34 and retinoblastoma-1 (RB1) protein] and fluorescence in situ hybridization (RB1 deletion). The patients ranged in age from 35 to 81 years (median 64 years). The male to female ratio was almost equal (14:11). All tumors with a known location were situated on the face with a special predilection for the nose. All cases were sporadic, with all patients having a single lesion and showing no clinical features of Birt–Hogg–Dubé syndrome. No case with available follow-up presented with a recurrence or an otherwise aggressive clinical course. Spindle cell stroma was immunohistochemically positive for CD34 in 16 of 20 cases, and 18 of 19 cases showed loss of RB1 staining in lesional spindle cells. Fluorescence in situ hybridization analysis detected RB1 gene heterozygous deletion in 6 of 20 cases. We conclude that despite the SCL-like appearance of the investigated cases, the majority of them supposedly represent genuine spindle cell predominant trichodiscomas with adipose tissue admixture. However, there was a subset of histopathologically indistinguishable cases with proved RB1 deletion, which likely represent SCL with trichodiscoma/fibrofolliculoma-like epithelial/adnexal induction rather than spindle cell predominant variant of trichodiscoma.

Primary Cutaneous Acral CD8+ T-Cell Lymphoma—A Single Center Review of 3 Cases and Recent Literature Review Abstract: The recently published 2016 revision of the WHO classification of lymphoid neoplasms includes primary cutaneous acral CD8-positive T-cell lymphoma (PCATCL) as a provisional entity. This is a rare indolent lymphoma characterized by papules or nodules on the ear and a dermal infiltrate of CD8-positive T-lymphocytes with cytotoxic marker expression. A retrospective review of a single institutional experience with PCATCL identified 3 patients (mean age 54; range 49–62) with papules or nodules on the ear. Lesional biopsies demonstrated a dense diffuse dermal infiltrate of atypical lymphocytes with a Grenz zone in 2 cases and focal epidermotropism in 1 case. The atypical lymphocytes were predominantly CD3 and CD8 positive with expression of cytotoxic marker TIA1. Staging evaluation failed to reveal systemic disease. Two patients underwent local excision, and the third received local radiation therapy all with complete response and no disease recurrence at last follow-up 3 months (range 2–5 months). Our cases add to the existing limited literature on the clinical and histopathological features of PCATCL. We also performed an updated systematic literature view of the entity.

Collision of Subungual Neurofibroma and Onychomatricoma: S100 Positivity as a Clue Abstract: We present a 41-year-old man with a hemionychodystrophy of the first toe, appearing as a longitudinal thickening of the nail plate, overcurved and with holes in its thickened free margin, thus leading to the clinical diagnosis of onychomatricoma. Complete excision showed typical nail plate of onychomatricoma and, underlying it, curvy disorganized neural-looking fascicles without atypia and with diffuse positivity for S100, interpreted as subungual neurofibroma (NF). Subungual NF is a very rare tumor, with only 12 previous cases reported. Its diagnosis is based on histopathology, as the tumor presents waves or whorls of disorganized neural-looking cells positive for S100. Regarding onychomatricoma, it is characterized by typical glove finger digitations (which were present in our case) and an underlying stroma composed by a cellular superficial layer (this layer expresses CD34 but not CD99) and a more sclerotic and deeper area. As we did not find information on S100 expression in the stroma of onychomatricoma, we have stained 4 typical cases, and all were negative with S100 and positive with CD34, as expected. In conclusion, as “subungual NF” is so rare and, in our case, seems to collide with a typical onychomatricoma, we recommend adding S100 staining to properly characterize tumors involving nail plate, to detect underlying neural tumors, as has happened in our case.

Granulomatous Reaction to Intralesional Kenalog (Triamcinolone) Injection in Acne: A Case Report Abstract: Intralesional Kenalog (triamcinolone) injection is a useful treatment for several skin conditions. Although dermal deposition of triamcinolone has been described in the literature, histopathologic findings of foreign body reactions to it have seldom been reported. Here, we describe a case of a granulomatous reaction to the intralesional injection of triamcinolone acetonide in the treatment of nodulocystic acne.

Primary Orbital Synovial Sarcoma Mimicking a Periocular Cyst Abstract: Synovial sarcoma (SS) is a high-grade soft-tissue sarcoma occurring predominantly in older children and young adults. Only approximately 7% occur in the head and neck region, with SS representing less than 0.1% of all head and neck cancers. Orbital location is exceedingly rare with only 8 cases reported so far in the literature. It is noted for its propensity for late local recurrences and metastases. Histologically, SS is monophasic, biphasic, or poorly differentiated and harbors a specific chromosomal translocation t(X;18)(p11.2;q11.2) in >95% of cases. In this article, we describe a case of monophasic SS primarily arising in the left supero-nasal orbital region in a 24-year-old woman, clinically mistaken for a periocular cyst. The case is peculiar for its highly unusual location and for its clinical deceptively benign appearance.

Necrotizing Granulomas in a Patient With Psoriasis and Sarcoidosis After Adalimumab—Medication-Induced Reaction or Reactivation of Latent Disease? Abstract: In this report, we describe a case of a patient with a clinical history of systemic sarcoidosis and psoriasis who developed biopsy-confirmed perforating and necrotizing cutaneous granulomas after 12 months of treatment with adalimumab, a tumor necrosis factor-alpha–inhibiting, anti-inflammatory, biologic medication, prescribed for the patient's psoriasis. Although rare reports of a “sarcoidosis-like” reaction associated with select tumor necrosis factor-alpha agents exist, to the best of our knowledge, perforating and necrotizing cutaneous granulomas after treatment with adalimumab has not been previously reported. Given the patient's history of systemic sarcoidosis, the differential diagnosis includes reactivation of latent sarcoidosis with adalimumab as a trigger.

Subcutaneous Panniculitis-Like T-Cell Lymphoma With Granulomas as the Predominant Feature Abstract: Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare primary cutaneous lymphoma preferentially localized in the subcutaneous adipose tissue and composed of cytotoxic T cells with an α/β immunophenotype. The neoplastic T cells can be variably admixed with other inflammatory cells, including histiocytes, which can rarely form noncaseating granulomas. We present a case of SPTCL in which granulomas are the predominant feature, composing 75%–80% of the inflammatory infiltrate. The top differential diagnoses included infectious and autoimmune etiologies. However, special stains for microorganisms were negative, and immunohistochemical analysis of the atypical lymphocytes showed a CD3+, CD8+, TIA-1+, T-cell receptor (TCR) beta+, and CD4− infiltrate with a high Ki67 proliferation index of approximately 30%. TCR gene rearrangement studies by polymerase chain reaction with confirmation by high-throughput sequencing were necessary to exclude an autoimmune etiology, specifically lupus erythematosus panniculitis. To the best of our knowledge, only 1 other case of SPTCL with prominent granulomas has been reported in the literature. It is important for dermatopathologists to recognize this presentation of SPTCL. SPTCL with predominant granulomas should be included in the differential diagnosis of granulomatous panniculitis along with infectious and autoimmune panniculitides as well as other granulomatous lymphomas.

Spontaneous Hair Repigmentation in an 80-Year-Old Man: A Case of Melanoma-Associated Hair Repigmentation and Review of the Literature Abstract: Spontaneous hair repigmentation of physiologically white or gray hair is a rare occurrence that may be associated with melanoma in elderly individuals. We present the first case of this phenomenon in a man. A gray-haired, 80-year-old man presented to dermatology clinic with a 3-cm lock of black hair on his vertex scalp that developed over 1 year. Punch biopsies showed an increase in junctional dendritic melanocytes with rare pagetoid cells and extension along the follicular outer root sheath epithelium and interfollicular epidermis, associated with prominent dendritic melanocytic hyperplasia and pigment-containing melanocytes within the hair bulbs. Although the findings on the biopsies were not diagnostic of melanoma in situ, an irregular interfollicular distribution of melanocytes was concerning for an adjacent atypical process. A complete excision was performed and revealed melanoma in situ, lentigo maligna type. Rare reports describe spontaneous hair repigmentation as a harbinger of lentigo maligna in women. Repigmentation can occur in the setting of proliferation of malignant pigment-producing melanocytes or by paracrine stimulation of benign bulbar melanocytes through receptor tyrosine kinase KIT activation. Presence of prominent dendritic melanocytic hyperplasia and pigment-containing melanocytes within the hair bulbs in our patient's biopsies was suggestive of paracrine or physiologic stimulation of bulbar melanocytes. Given the importance of early melanoma detection and the low visibility of the scalp, this report raises awareness of an extraordinary presentation of lentigo maligna and exemplifies the importance of close clinicopathologic correlation to ensure optimal clinical management and patient outcome.