Urticarial mycosis fungoides: A distinctive presentation with blood involvement and a peculiar immunophenotype.

Mycosis fungoides (MF) has been widely reported to mimick a considerable number of different dermatoses, including scarring alopecia, bullous dermatoses or cysts, and comedones. In atypical presentations, histopathology is essential for the diagnosis. We present two cases of MF with clinical urticarial lesions and a striking blood involvement that responded to mogamulizumab treatment. Histopathologically, both cases had classic MF features and shared a peculiar immunophenotype, with positivity for CD25 and FOXP3. Differential diagnoses included urticarial lymphomatoid drug reactions and other lymphomas, like T-cell prolymphocytic leukemia, atypical Sézary syndrome, or adult T-cell lymphocytic leukemia. A low suspicion threshold is necessary for the diagnosis of atypical presentations of MF.

Cutaneous eruption with reactive endothelial atypia due to emerging targeted cancer therapies: Report of two cases with clinico-pathologic correlation.

Targeted anticancer therapy is being used with greater frequency and dermatologic toxicities are among the most frequent adverse events of these drugs. However, histopathological features of these adverse events are not yet well characterized. We present two cases of clinically different cutaneous toxicities on two patients with hematologic neoplasia. They were treated with different drugs and in both cases medications shared inhibition of PI3K as mechanism of action. The skin biopsy specimen showed endothelial cell atypia with large nuclei and mitotic figures. To the best of our knowledge, no other cases with these striking histopathologic findings have been reported with PI3K inhibitors or other anticancer targeted therapy.

Toker cell hyperplasia in Zuska disease: A tricky association.

Toker cells (TCs) are sometimes present in the nipple epidermis as oval cells with pale cytoplasm and roundish nuclei. In most cases, TCs may be easily distinguished from cancerous cells of Paget disease of the nipple (PCs). Especially in TC hyperplasia, in which mild-to-moderate atypia may be present, it may be challenging to distinguish between TCs and PCs. The combination of chronic inflammatory changes in the nipple, in the context of Zuska disease, and TC hyperplasia, may easily lead to an erroneous diagnosis of mammary Paget disease.

Three additional cases of non-neural granular cell tumor with novel immunohistochemical findings.

BACKGROUND: Non-neural granular cell tumor (NNGCT) is an uncommon neoplasm of controversial histogenesis and its histopathologic differential diagnosis includes, in addition to conventional GCT, other dermal tumors that may exhibit granular cell change. METHODS: Three patients with a diagnosis of NNGCT were identified in the authors' files. Hematoxylin and eosin-stained sections and immunohistochemical studies were performed. RESULTS: Histopathological study of the three lesions showed dermal proliferation of granular cells arranged in thick fascicles between collagen bundles. The lesions showed positivity for Factor XIIIa, CD163, CD68, NKIC3, vimentin, ALK, fascin, and cyclin D1. CONCLUSION: To our knowledge, positivity for cyclin D1 has not been reported to date in NNGCT. In borderline cases, where the diagnosis is unclear despite histopathologic and immunohistochemical findings, positivity for cyclin D1 may favor the diagnosis of NNGCT. Further investigations to assess the differentiation of this rare neoplasm are needed.

Syringocystadenoma papilliferum associated with verrucous carcinoma of the skin in the same lesion: Report of four cases.

The association of syringocystadenoma papilliferum (SCAP) with verrucous carcinoma (VC) of the skin in the same lesion is a rare, but well-documented event. Although human papillomaviruses (HPV) have been proposed to have an etiologic role in the development of the verrucous proliferations associated with SCAP, most of the immunohistochemical and molecular studies have failed to show the presence of their genomic material in these lesions. We report a series of four cases of SCAP associated with VC in anogenital lesions. In two of the cases, we demonstrated the presence of the BRAF V600E mutation by polymerase chain reaction and immunohistochemistry, both in the glandular and in the squamous component. No HPV-related histopathologic changes were found, nor could the presence of viral DNA be showed.

Acrolocalized variant of lichen sclerosus initially manifesting as degenerative collagenous plaques of the hands.

Lichen sclerosus involving the hands is very uncommon. On the other hand, degenerative collagenous plaques of the hands is a rare condition characterized by keratotic, translucent papules in linear array, on the radial border of the hands. Histopathologically, lesions of degenerative collagenous plaques of the hands show increased collagen bundles in upper half of the dermis and dermal elastosis. We describe the clinical and histopathological progression experienced by a woman who initially presented lesions with clinical and histopathological appearance of degenerative collagenous plaques of the hands, which evolved into characteristic lichen sclerosus. We propose that some cases of the so-called degenerative collagenous plaques of the hands may represent an acrolocalized lichen sclerosus at an early stage.

Langerhans cell histiocytosis and multiple reticulohistiocytomas in a patient with TAR syndrome: An association not previously described.

We describe a patient with thrombocytopenia-absent radius (TAR) syndrome, multisystemic Langerhans cell histiocytosis and multiple reticulohistiocytomas. A mutational study by massive sequencing identified the Val600Glu (V600E) BRAF mutation in the Langerhans cell histiocytosis lesions, but no molecular alterations were found in the reticulohistiocytoma lesions. The concomitant presence in the same patient of more than one type of histiocytosis from two different groups recognized in the most recent Histiocyte Society classification is an extremely rare event. Our case is the first reported case of multisystemic Langerhans cell histiocytosis and multiple reticulohistiocytomas in a patient with TAR syndrome.

Plaque-Like Pilar Sheath Acanthoma: Histopathologic and Immunohistochemical Study of 3 Unusual Cases.

Pilar sheath acanthoma is an uncommon, benign follicular neoplasm that frequently presents as a solitary lesion. This neoplasm usually appears on the skin around the upper lip of elderly patients. Histopathologically, the neoplasm usually shows a cystic configuration with epithelial lobules resembling to those of the outer root sheath of the hair follicle at the level of the isthmus emanating radially from the cyst wall. We present 3 peculiar cases of a pilar sheath acanthoma showing a plaque-like architecture because the lesions exhibited a horizontal configuration. To our knowledge, there are no previously reported examples of plaque-like pilar sheath acanthoma.

Dermal Hyperneury and Multiple Sclerotic Fibromas in Multiple Endocrine Neoplasia Type 2A Syndrome.

Importance: Multiple endocrine neoplasia type 2 (MEN 2) syndrome is an autosomal dominant, hereditary cancer disorder caused by germline mutations in the RET (formerly MEN2A, MEN2B) proto-oncogene located on chromosomal band 10q11.21. Two distinct clinical forms have been described as the following phenotypes: multiple endocrine neoplasia type 2A (MEN 2A) and multiple endocrine neoplasia type 2B (MEN 2B) syndromes. The common and necessary nexus that defines these 2 phenotypes is the presence of medullary thyroid carcinoma (MTC). The familial MTC type of MEN 2 syndrome was included within the spectrum of MEN 2A syndrome. Cutaneous manifestations of MEN 2A syndrome include macular amyloidosis, whereas MEN 2B syndrome is traditionally linked to multiple mucosal neuromas. Objectives: To describe a family with cutaneous manifestations not previously described in patients with MEN 2A syndrome and to discuss the association of this disorder with Cowden syndrome. Design, Setting, and Participants: Clinicopathologic correlation of cutaneous lesions and genetic studies in 11 members of a family with familial MTC. Interventions: Cutaneous lesions were histopathologically and immunohistochemically studied. Genetic screening for a germline mutation at the RET gene was performed in 11 family members. Main Outcomes and Measures: Identification of cutaneous lesions not previously described in patients with MEN 2A syndrome. Results: This family of 11 individuals with familial MTC type of MEN 2A syndrome demonstrated the moderate risk RET p.Val804Met (protein valine at residue 804 replaced by methionine) genetic mutation, with 2 of the relatives presenting with dermal hyperneury, cutaneous lesions classically described in MEN 2B syndrome, and 1 relative also showing multiple sclerotic fibromas, a cutaneous manifestation of PTEN (phosphatase and tensin homologue) hamartoma-tumor syndrome. Conclusions and Relevance: Dermal hyperneury and multiple sclerotic fibromas should be added to the list of cutaneous manifestations of patients with the familial MTC type of MEN 2A syndrome.

Genital folliculo-sebaceous cystic hamartoma: A claim of the stroma as a clue in the diagnosis of proliferations with follicular differentiation.

Folliculo-sebaceous hamartomas comprise a series of entities whose boundaries are imprecise. We present the clinical case of a folliculo-sebaceous cystic hamartoma of genital localization where the diagnosis was established based on the epithelial proliferation, but mostly, on the characteristic stroma. Because this lesion lacked of the cystic component, we mention the most frequent differential diagnoses and review the literature of the few cases published on this infrequent localization.