Diffuse neurofibroma with hypertrichosis in a toddler.

Diffuse neurofibroma is a rare type of neurofibroma uncommonly reported in infancy. It is a slow growing tumor originating in the peripheral nerve sheath. We present the case of a 17-month-old boy with diffuse neurofibroma of the scalp associated with hypertrichosis. His genetic and clinical workup for neurofibromatosis was negative.

Cutaneous VCL::ALK fusion ovoid-spindle cell neoplasm.

Cutaneous VCL::ALK fusion spindle (ovoid) cell tumor is unique. Recently emerged RAS::MAP tyrosine kinase fusion sarcomas more commonly involve subcutis, skeletal muscle and even bone. We share our experience with a novel cutaneous VCL::ALK spindle cell tumor. An 11-year-old male presented with a back pedunculated pink-red papule thought to be a pyogenic granuloma. Biopsy histopathology revealed an epithelial collarette with pedunculated tumor extending to deep dermis/subcutis interface. The combination of spindled and epithelioid cells, an ovoid myopericytoid appearance within myxoid to collagenous stroma, low to moderate MIB1 and focal S100 protein without SOX10 immunostaining, were suggestive of a novel RAS::MAPK tyrosine kinase fusion sarcoma that is well described. ALK immunostain being positive, a next-generation sequencing comprehensive fusion panel was performed to reveal a VCL::ALK fusion. While epithelioid fibrous histiocytoma shares this fusion and similar dermal location and collarette pedunculation, this and other entities were excluded by older patient age, deeper dermal involvement, ovoid-to-spindled morphology, central pericytoid vasculature, myxoid stroma, moderate cellularity with low to moderate MIB1 expression, superficial ulceration, and focal S100 protein expression. Complete excision was performed with favorable follow-up to date. This novel VCL::ALK fusion spindle (ovoid) cell tumor of the dermis is best considered as part of the recently emerged RAS::MAP tyrosine kinase fusion sarcomas.

Two cases of adenodermatofibroma.

Dermatofibromas (DF) are common skin lesions composed of a dermal proliferation of fibroblasts and histiocytes. Among the variants of DFs, adenodermatofibroma are characterized by a dense proliferation of fibroblasts and histiocytes admixed with entrapped dilated glandular structures. We report two additional cases of adenodermatofibromas, review the literature, theorize on the histopathogenesis of this variant, and suggest that there are different patterns among adenodermatofibromas, from primarily cystic to primarily glandular.

SOX10 Immunostaining in granulomatous dermatoses and benign reactive lymph nodes.

BACKGROUND: SOX10 immunostaining has been considered a highly sensitive and specific marker for melanoma. But there is evidence suggesting that SOX10 positive cells can be present in dermal scars. Therefore, we investigated whether non-melanocytic cell types present in chronic inflammatory processes or benign lymph nodes express SOX10. METHODS: We retrospectively selected 20 benign lymph nodes and 20 cutaneous granulomatous dermatoses. SOX10, CD68, and Melan-A immunohistochemistry was performed in all cases. RESULTS: Scattered SOX10 positivity was found in 85% of lymph nodes, specifically in subcapsular and medullary sinuses and in 85% of granulomatous dermatoses. In granulomatous dermatoses, the Melan-A stain did not label the scattered SOX10 positive cells and it was difficult to determine if CD68 was co-expressed on the SOX10 positive cells. In the lymph nodes, the SOX10 positive cells did not co-express Melan-A or CD68. CONCLUSIONS: We report SOX10 positive cells detected in granulomatous dermatoses and benign lymph nodes. In lymph nodes, SOX10 positive cells were exclusively in subcapsular and medullary sinuses. Therefore, SOX10 is an excellent stain for evaluation of metastatic melanoma with the caveat that positivity in subcapsular and medullary sinuses can be of non-melanocytic origin; the use of additional melanocytic markers is recommended in this situations.

Safety and immunogenicity of a varicella vaccine without human serum albumin (HSA) versus a HSA-containing formulation administered in the second year of life: a phase III, double-blind, randomized study.

BACKGROUND: A new formulation of the live-attenuated varicella vaccine Varilrix (GSK) produced without human serum albumin (HSA) was developed to minimize a theoretical risk of transmission of infectious diseases. A previous study showed that the vaccine was immunologically non-inferior to the HSA-containing vaccine and well-tolerated in toddlers; low-grade fever was numerically higher in children receiving the vaccine without HSA, but the study lacked power to conclude on this difference. METHODS: In this phase III, double-blind, multi-center study, healthy 12-23-month-olds were randomized (1:1) to receive two doses of the varicella vaccine without (Var-HSA group) or with HSA (Var + HSA group) at days 0 and 42. The primary objective compared safety of the vaccines in terms of incidence of fever > 39.0 °C in the 15-day period post-first vaccination. The objective was considered met if the upper limit of the 95% confidence interval for the between-group difference in the incidence of fever > 39.0 °C was ≤5% (Var-HSA group minus Var + HSA group). Safety, reactogenicity and immune responses were evaluated. RESULTS: Six hundred fifteen children in the Var-HSA group and 616 in the Var + HSA group received ≥1 vaccination. Fever > 39.0 °C was reported in 3.9 and 5.2% of participants in the Var-HSA and Var + HSA groups, with a between-group difference of - 1.29 (95% confidence interval: - 3.72-1.08); therefore, the primary objective was achieved. Fever rates post-each dose and the incidence of solicited local and general adverse events (AEs) were comparable between groups. Unsolicited AEs were reported for 43.9 and 36.5% of children in the Var-HSA group and 45.8 and 36.0% of children in the Var + HSA group, during 43 days post-dose 1 and 2, respectively. Serious AEs occurred in 2.1% (group Var-HSA) and 2.4% (group Var + HSA) of children, throughout the study. In a sub-cohort of 364 children, all had anti-varicella-zoster virus antibody concentrations ≥50 mIU/mL post-dose 2; comparable geometric mean concentrations were observed between the groups. CONCLUSIONS: The varicella vaccine formulated without HSA did not induce higher rates of fever during the 15 day-post-vaccination period, as compared with the original HSA-containing vaccine. The two vaccines displayed similar safety and immunogenicity profiles in toddlers. TRIAL REGISTRATION: NCT02570126 , registered on 5 October 2015 (www.clinicaltrials.gov).

Scurvy: a rare case in an adult.

A 69-year-old man presented with unilateral calf pain, swelling, and erythematous rash. He was initially treated with antibiotics for suspected cellulitis. A venous duplex ultrasound, performed to exclude deep venous thrombosis, revealed multiple heterogeneous hypoechoic foci of unknown etiology throughout the calf musculature. His condition did not improve with antibiotics, instead progressing to a necrotic ulcer along the medial malleolus. Clinical suspicion of vascular insufficiency or vasculitis prompted an extensive imaging work-up. CT and MRI revealed the intramuscular abnormalities observed on previous ultrasound represented foci of intramuscular hemorrhage. Marrow signal abnormality was also noted in the proximal tibia. A punch biopsy of the skin rash ultimately demonstrated distorted hair follicles with perifollicular inflammation and hemorrhage concerning for scurvy. The diagnosis was confirmed by low vitamin C levels and dietary history. A resurgence of scurvy has occurred in the pediatric population in recent years. However, this diagnosis remains uncommon in adults, with limited reports of the potential advanced imaging findings in the current literature.

Kaposiform hemangioendothelioma with Kasabach-Merritt phenomenon in an infant: Successful treatment with prednisolone, vincristine, and addition of sirolimus.

A full-term newborn with kaposiform hemangioendothelioma (KHE) affecting the right thigh with thrombocytopenia due to Kasabach-Merritt phenomenon (KMP) was referred to our center. After biopsy, he rapidly evolved to severe thrombocytopenia and severe coagulopathy. Standard therapy was initiated with prednisolone and vincristine. His coagulopathy worsened to life-threatening hemorrhage necessitating aggressive blood products replacement. Sirolimus was added; he became transfusion independent with no further bleeding and reduction in tumor size. Addition of sirolimus to treatment of vascular anomalies with hemostatic complications should be considered as part of early treatment for patients with KMP/KHE.

An independent validation of a gene expression signature to differentiate malignant melanoma from benign melanocytic nevi.

BACKGROUND: Recently, a 23-gene signature was developed to produce a melanoma diagnostic score capable of differentiating malignant and benign melanocytic lesions. The primary objective of this study was to independently assess the ability of the gene signature to differentiate melanoma from benign nevi in clinically relevant lesions. METHODS: A set of 1400 melanocytic lesions was selected from samples prospectively submitted for gene expression testing at a clinical laboratory. Each sample was tested and subjected to an independent histopathologic evaluation by 3 experienced dermatopathologists. A primary diagnosis (benign or malignant) was assigned to each sample, and diagnostic concordance among the 3 dermatopathologists was required for inclusion in analyses. The sensitivity and specificity of the score in differentiating benign and malignant melanocytic lesions were calculated to assess the association between the score and the pathologic diagnosis. RESULTS: The gene expression signature differentiated benign nevi from malignant melanoma with a sensitivity of 91.5% and a specificity of 92.5%. CONCLUSIONS: These results reflect the performance of the gene signature in a diverse array of samples encountered in routine clinical practice. Cancer 2017;123:617-628. © 2016 American Cancer Society.

Keratoacanthoma-Like Growths of Incontinentia Pigmenti Successfully Treated with Intralesional Methotrexate.

We report the case of a 17-year-old girl with incontinentia pigmenti who developed multiple large hyperkeratotic tumors within Blaschkoid hyperpigmented patches on her left leg. Biopsy demonstrated an endoexophytic nodule with irregular invaginations of keratinizing squamous epithelium and a central keratin-filled crater, consistent with keratoacanthoma-like lesions of incontinentia pigmenti. The tumors were successfully treated with intralesional methotrexate.

Cutaneous involvement in multiple myeloma (MM): A case series with clinicopathologic correlation.

BACKGROUND: Disease-specific skin lesions are rare in patients with multiple myeloma (MM). OBJECTIVE: We sought to further characterize the clinical and pathologic features of patients with cutaneous involvement with MM. METHODS: We identified 13 patients with cutaneous lesions of MM. RESULTS: Cutaneous lesions consisted of pink, red, and violaceous papules, nodules, and/or plaques that varied in size. Histopathology revealed atypical plasma cells with occasional plasmablastic features. MM had aggressive biologic features and was at an advanced stage in the majority of patients. Despite aggressive management, including chemotherapy and stem-cell transplantation, most patients died of progressive disease within a few months after the development of cutaneous lesions. LIMITATIONS: The study group was relatively small. CONCLUSIONS: Cutaneous involvement with MM is associated with aggressive biologic behavior and short survival.

Apocrine Fibroadenoma on the Face: Case Report and Review of the Literature.

Apocrine fibroadenoma (AFA) is a common benign entity found in the breast but is rarely seen at other sites. Several studies have documented cases in the anogenital region, but to date, there have been only 4 cases (excluding the current case) of an AFA located in the skin on other parts of the body. The authors present a case of a 66-year-old woman with a 6-year history of a slow growing red nodule on her face. The histopathologic diagnosis was consistent with an AFA. An extensive review of the literature to elucidate a possible pathogenesis of these lesions and relationship to the anogenital counterparts is presented.

Umbilical Granuloma in a 2-Month-Old Patient: Histopathology of a Common Clinical Entity.

Umbilical granulomas are the most common anomaly of the umbilicus in neonates and infants. These lesions are characterized by an overgrowth of granulation tissue that persists at the base of the umbilical cord after its separation. Histologically, they consist of granulation tissue, which is composed of fibroblasts, inflammatory cells, and vascular endothelial cells set in an edematous stroma. Although umbilical granulomas are commonly seen clinically, there are no reports of their histopathology in the literature. The authors present the histology of this clinical finding in a 2-month-old infant, as it is important for the pathologist to be aware of this benign entity and distinguish it from other umbilical anomalies that may be of greater clinical significance.

Gamma-delta T-cell lymphoma arising in a long-standing cutaneous plaque.

The precise classification and characterization of primary cutaneous gamma-delta T-cell lymphoma (PCGD-TCL) has been hindered by clinical and morphologic features that overlap with other lymphomas, especially subcutaneous panniculitis-like T cell lymphoma (SPTCL). The recent World Health Organization/European Organization for Research and Treatment of Cancer (WHO/EORTC) classification distinguishes the more aggressive PCGD-TCL from the usually indolent SPTCL, however. We report a 30-year-old woman with an indurated violaceous plaque on the left cheek that had been present for several years. Biopsies showed a dense lymphocytic infiltrate involving the subcutis and dermis that consisted mostly of small and medium-sized lymphocytes, some with irregular nuclear contours and dense chromatin. These cells were positive for TIA-1, TCR-gamma and CD8, but negative for beta-F1 and granzyme-B. Staging with positron emission tomography-computed tomography (PET/CT), CBC and bone marrow with flow cytometry identified lymphadenopathy as well as blood and marrow involvement by an abnormal TCRgd-positive T-cell proliferation (Ann Arbor Stage IV). The patient's history of a long-standing lesion in this case is unusual, in that gamma-delta T-cell lymphomas are typically rapidly progressive neoplasms. As such, it raises the possibility of 'transformation' of a long-standing inflammatory process into an overt lymphoma.

Lentigo Maligna Melanoma With Local and Distant Blue Nevus-like Metastases.

Melanoma or melanoma metastases can rarely mimic blue nevi clinically and/or histologically, presenting a diagnostic pitfall for both the clinician and the dermatopathologist. We report a case of an invasive lentigo maligna melanoma with subsequent development of multiple, cutaneous blue nevus-like localized metastases followed by a distant metastasis, heralding widespread systemic metastases.