Angiolymphoid hyperplasia with eosinophilia and Kimura disease: A case report and literature review.

Angiolymphoid hyperplasia with eosinophilia (ALHE) is a benign vascular proliferative condition, typically presenting as subcutaneous nodules in the head and neck region of middle-aged women. Kimura disease (KD) is a benign condition that presents with subcutaneous nodules in a similar distribution with lymphadenopathy and eosinophilia, typically in Asian adult males. These diseases are often discussed together, including whether they exist on a spectrum or if they represent separate disease entities. Both are very rare in the pediatric population; in this report we highlight the case of a 10-year-old Caucasian male presenting with ALHE and KD.

Foreign body reaction toward hydrophilic polymer at the site of endovascular procedure: A report of two cases.

Hydrophilic polymer-coated devices have been increasingly utilized for various endovascular procedures, however not been without adverse effects. We report two cases of subacute cutaneous lesions on the neck encountered in our dermatology clinic. Histopathologic findings were significant for a nodular aggregate of epithelioid histiocytes and lymphocytes with numerous foreign body giant cells in the dermis. The granulomatous infiltrate was associated with an amorphous basophilic non-polarizable material. Further chart review reveals both patients receiving a central venous procedure in the past, thus attributing the hydrophilic polymers as the likely source of the foreign material found at the insertion site. Our cases contrast to the more commonly reported distal embolization by these hydrophilic polymer layers. We suspect the incidence of retained hydrophilic polymer at the site of prior endovascular procedures may be underreported in the literature with the more inconspicuous presentations. Therefore, retained foreign material should be considered by both treating physicians and dermatopathologists in presenting cases of lesions that occur at common sites of endovascular procedures.

Poroid adnexal skin tumors with YAP1 fusions exhibit similar histopathologic features: A series of six YAP1-rearranged adnexal skin tumors.

BACKGROUND: Adnexal skin tumors are diagnostically challenging with few known molecular signatures. Recently, however, YAP1-MAML2 and YAP1-NUTM1 fusions were identified in poroid adnexal skin tumors. METHODS: Herein, we subjected eight poroid adnexal skin tumors (three poromas and five porocarcinomas) to fusion gene analysis by whole transcriptome sequencing and next-generation DNA sequencing analysis. RESULTS: YAP1 fusions were identified in six cases. YAP1-NUTM1 fusions were identified in two poromas and three porocarcinomas. A single case of porocarcinoma harbored a YAP1-MAML2 fusion. Two cases were negative for gene fusion. All cases that harbored YAP1-NUTM1 fusions showed nuclear protein in testis (NUT) expression by immunohistochemistry, with NUT being negative in the YAP1-MAML2-positive case. In this case series, we provide a detailed histopathologic description of six YAP1-fused poroid skin tumors, which we show harbor reproducible histopathologic features, to include broad, bulbous tumor tongues with admixtures of basaloid, poroid cells punctuated by squamatized cuticles and ductules, with uniform tumor nuclei featuring frequent grooves and pseudonuclear inclusions. CONCLUSIONS: Awareness of the characteristic histopathologic features of YAP1-fused poroid adnexal skin tumor is a step toward a more reproducible classification of adnexal skin tumors as well as a step toward targeted therapy for metastatic and/or unresectable examples of this poroid group of neoplasms.

Indurated Plaque with Bullae Formation on the Left Arm.

A 72-year-old white man presented to the clinic with a tender, pruritic lesion on the upper part of his left arm that had progressively worsened over 4 months. Physical examination revealed an erythematous to violaceous, indurated, and sclerotic plaque with multiple foci of crusting and erosions (Figure 1). The patient denied any recent trauma, travel, fever, chills, weight loss, or constitutional symptoms. Before presentation, he had undergone treatment with cephalexin, prednisone, and doxycycline without reported improvement. Laboratory studies were negative for antinuclear antibody and SCL70 antibody; however, an absolute eosinophilia of 1478/uL was noted.

Sebaceous Carcinoma of the Eyelid.

BACKGROUND: Periocular sebaceous carcinoma (PSC) is a rare but aggressive neoplasm that tends to clinically and histopathologically mimic other conditions. PSC can be challenging to diagnose using histomorphology alone given its overlap with 2 more common tumors that occur in this area (basal cell carcinoma [BCC] and squamous cell carcinoma [SCC]). Use of immunohistochemistry can help resolve this differential diagnosis. METHODS: A review of the literature was performed, focusing on the epidemiology, morphology, and immunohistochemical features of PSC. RESULTS: The most useful immunostains in the differential diagnosis of PSC are epithelial membrane antigen, Ber-Ep4, androgen receptor (AR), and adipophilin. To discern PSC from BCC, one should use EMA, Ber-Ep4, AR, and adipophilin, whereas discerning PSC from SCC can be achieved by evaluating AR and adipophilin. In addition, p53 and ERBB2 (formally known as HER2/neu) are other potentially useful immunohistochemical markers for the differential diagnosis of PSC. CONCLUSIONS: Use of new immunohistochemical techniques, as well as the elucidation of molecular alterations, such as the presence of ERBB2 amplification, will advance our understanding of PSC.

Vascular tumors have increased p70 S6-kinase activation and are inhibited by topical rapamycin.

Vascular tumors are endothelial cell neoplasms whose cellular and molecular mechanisms, leading to tumor formation, are poorly understood, and current therapies have limited efficacy with significant side effects. We have investigated mechanistic (mammalian) target of rapamycin (mTOR) signaling in benign and malignant vascular tumors, and the effects of mTOR kinase inhibitor as a potential therapy for these lesions. Human vascular tumors (infantile hemangioma and angiosarcoma) were analyzed by immunohistochemical stains and western blot for the phosphorylation of p70 S6-kinase (S6K) and S6 ribosomal protein (S6), which are activated downstream of mTOR complex-1 (mTORC1). To assess the function of S6K, tumor cells with genetic knockdown of S6K were analyzed for cell proliferation and migration. The effects of topical rapamycin, an mTOR inhibitor, on mTORC1 and mTOR complex-2 (mTORC2) activities, as well as on tumor growth and migration, were determined. Vascular tumors showed increased activation of S6K and S6. Genetic knockdown of S6K resulted in reduced tumor cell proliferation and migration. Rapamycin fully inhibited mTORC1 and partially inhibited mTORC2 activities, including the phosphorylation of Akt (serine 473) and PKCα, in vascular tumor cells. Rapamycin significantly reduced vascular tumor growth in vitro and in vivo. As a potential localized therapy for cutaneous vascular tumors, topically applied rapamycin effectively reduced tumor growth with limited systemic drug absorption. These findings reveal the importance of mTOR signaling pathways in benign and malignant vascular tumors. The mTOR pathway is an important therapeutic target in vascular tumors, and topical mTOR inhibitors may provide an alternative and well-tolerated therapy for the treatment of cutaneous vascular lesions.

Gastrointestinal histoplasmosis in a hepatitis C-infected individual.

Gastrointestinal histoplasmosis is a rare manifestation of this fungal infection, typically identified in immunocompromised patients, such as those with HIV/AIDS. Here, we report a case of disseminated histoplasmosis with gastrointestinal involvement in a Hepatitis C-infected patient. The fungal agent was confirmed to be Histoplasma capsulatum by a DNA probe assay performed on a bone marrow sample. We propose that this fungal disease should be kept on the differential of patients infected with the Hepatitis C virus, as it has been reported to have numerous damaging effects on the adaptive immune system.

Granuloma annulare mimicking multicentric reticulohistiocytosis.

We describe a patient with granuloma annulare (GA) who presented with firm periungual papules mimicking "coral beads", a characteristic sign of multicentric reticulohistiocytosis (MRH). We highlight the importance of distinguishing between GA and MRH because the prognoses differ significantly.

Secondary syphilis: a case mimicking erythema multiforme clinically and pathologically.

Secondary syphilis, the hematogenous spread of Treponema pallidum, usually occurs 4-10 weeks after initial exposure. The skin is involved in 70% of cases, with maculopapular, vesiculobullous, and ulcerative morphologies possible at presentation, making the diagnosis of secondary syphilis challenging given its ability to mimic many other conditions. We present an atypical case of secondary syphilis that closely resembled erythema multiforme (EM) clinically and histologically.

Eccrine hidrocystomas presenting as multiple papules on the cheeks.

Hidrocystomas are common, benign adnexal neoplasms most frequently found on the eyelids, canthi, or periocular areas. Herein, we report a case of multiple hidrocystomas distributed over less common facial areas: cheeks and cutaneous lips.

Metachromatic leukodystrophy and its effects on the gallbladder: a case report.

Metachromatic leukodystrophy (MLD) is an autosomal recessive lysosomal storage disorder caused by a deficiency of arylsulfatase A enzyme. This deficiency leads to accumulation of sulfatides in the central nervous system and other organs, such as the gallbladder. Here the authors discuss a 9-year-old Middle Eastern patient with late-infantile-type MLD who presented with symptoms of cholecystitis. Radiographic studies revealed an enlarged gallbladder with a thickened wall and a pericholecystic fluid collection with peripheral calcifications. Gross examination of the gallbladder showed multiple small to medium-sized papillary projections involving the entire mucosal surface. Sections through the gallbladder wall revealed multilocular dilated mucin-producing cystic spaces. Microscopically, the mucosa showed numerous papillary projections with complex folds lined by mucin-producing cuboidal to tall columnar cells. The cystic spaces were composed of numerous markedly distended Rokitansky-Aschoff sinuses filled with mucin. Ultrastructurally, the epithelial cells and macrophages showed frequent secondary lysosomes containing closely packed lamellar amorphous to prismatic material with alternating leaflets and tubules, imparting a "herringbone" or "tuffstone" pattern. This case illustrates the features of gallbladder involvement in MLD and the potential role of ultrastructural examination in diagnosis of MLD.

A Mutational Survey of Acral Nevi.

IMPORTANCE: Acral skin may develop nevi, but their mutational status and association with acral melanoma is unclear. OBJECTIVE: To perform targeted next-generation sequencing on a cohort of acral nevi to determine their mutational spectrum. DESIGN, SETTING, AND PARTICIPANTS: Acral nevi specimens (n = 50) that had been obtained for diagnostic purposes were identified from the pathology archives of a tertiary care academic cancer center and a university dermatology clinic. Next-generation sequencing was performed on DNA extracted from the specimens, and mutations called. A subset of samples was stained immunohistochemically for the BRAF V600E mutation. RESULTS: A total of 50 nevi from 49 patients (19 males and 30 females; median [range] age, 48 [13-85] years) were examined. Analysis of the sequencing data revealed a high prevalence of BRAF mutations (n = 43), with a lower frequency of NRAS mutations (n = 5). Mutations in BRAF and NRAS were mutually exclusive. CONCLUSIONS AND RELEVANCE: In this cohort study, nevi arising on mostly sun-protected acral skin showed a rate of BRAF mutation similar to that of acquired nevi on sun-exposed skin but far higher than that of acral melanoma. These findings are in contrast to the well-characterized mutational landscape of acral melanoma.