Claudia I. Vidal

The histone variant macroH2A suppresses melanoma progression through regulation of CDK8

Cancer is a disease consisting of both genetic and epigenetic changes. Although increasing evidence demonstrates that tumour progression entails chromatin-mediated changes such as DNA methylation, the role of histone variants in cancer initiation and progression currently remains unclear. Histone variants replace conventional histones within the nucleosome and confer unique biological functions to chromatin. Here we report that the histone variant macroH2A (mH2A) suppresses tumour progression of malignant melanoma. Loss of mH2A isoforms, histone variants generally associated with condensed chromatin and fine-tuning of developmental gene expression programs, is positively correlated with increasing malignant phenotype of melanoma cells in culture and human tissue samples. Knockdown of mH2A isoforms in melanoma cells of low malignancy results in significantly increased proliferation and migration in vitro and growth and metastasis in vivo. Restored expression of mH2A isoforms rescues these malignant phenotypes in vitro and in vivo. We demonstrate that the tumour-promoting function of mH2A loss is mediated, at least in part, through direct transcriptional upregulation of CDK8. Suppression of CDK8, a colorectal cancer oncogene, inhibits proliferation of melanoma cells, and knockdown of CDK8 in cells depleted of mH2A suppresses the proliferative advantage induced by mH2A loss. Moreover, a significant inverse correlation between mH2A and CDK8 expression levels exists in melanoma patient samples. Taken together, our results demonstrate that mH2A is a critical component of chromatin that suppresses the development of malignant melanoma, a highly intractable cutaneous neoplasm.

Cutaneous toxoplasmosis histologically mimicking graft-versus-host disease.

The dermatology service is frequently consulted to assess cutaneous eruptions after hematopoietic stem cell transplantation. We describe a case of cutaneous toxoplasmosis in a stem cell transplant patient where toxoplasmosis trophozoites elicited a reaction pattern mimicking an interface dermatitis. At first blush, these findings may be misinterpreted as either a reaction to a drug or graft-versus-host disease. We hope that this case will prove helpful for dermatopathologists in asserting the correct diagnosis of cutaneous toxoplasmosis-if left untreated or treated incorrectly, this disease has a dismal prognosis.

A unique case of a cutaneous lesion resembling mammary analog secretory carcinoma: a case report and review of the literature.

Mammary analog secretory carcinoma (MASC) is a rare type of salivary gland tumor named for its morphological and genetic similarity to secretory carcinoma of the breast. These tumors are most often found in the parotid gland but have been described in several other mucosal locations of the head and neck. In this case report, a cutaneous lesion most closely resembling MASC was found in a neck mass of a 64-year-old male patient without evidence of a primary salivary gland or oral tumor. The lesion was excised, and the patient remains disease free to date. This case depicts a rare tumor in the skin most closely mimicking MASC and brings additional awareness to dermatopathologists of this tumor.

p63 Immunohistochemisty Is a Useful Adjunct in Distinguishing Sclerosing Cutaneous Tumors

Cutaneous sclerosing epithelial neoplasms are often difficult to diagnose. Though various immunohistochemical markers have proved useful, some cases remain a diagnostic challenge. We aimed to assess the utility of p63 immunohistochemical staining in distinguishing microcystic adnexal carcinoma (MAC) from sclerosing basal cell carcinoma (SBCC) and desmoplastic trichoepithelioma (DTE). Biopsy samples from 20 SBCC, 10 DTE, and 5 MAC were examined after immunohistochemical staining with p63. Although all adnexal tumors examined demonstrated p63 expression, the pattern of staining was strikingly different in MAC when compared with other tumor types. MAC exhibited a scattered pattern with p63-positive cells around the periphery of tumor nests and minimal staining within the center of the tumor islands. This pattern was more pronounced at increased depth of infiltration into the dermis. A robust and consistent diffuse pattern of staining with p63 was observed in all SBCCs and DTEs. We believe this pattern reflects the multidifferentiation pathway of MAC, with eccrine/sebaceous differentiation occurring at deeper levels of the dermis. The different staining patterns of MACs compared with DTEs and SBCCs can thus serve as a useful diagnostic adjunct in difficult lesions.

Identification of Helicobacter pylori in skin biopsy of prurigo pigmentosa.

A 23-year-old Chinese man presented with a 3-year history of a pruritic eruption. On examination, pink urticarial papules associated with hyperpigmented reticulated patches were noted on his neck, back, and upper chest. Histopathology revealed vacuolar interface dermatitis and numerous gram-negative rods within a dilated hair follicle. The organisms were reactive with anti-Helicobacter pylori immunohistochemisty. The histologic findings and clinical presentation support the diagnosis of prurigo pigmentosa. Additional testing demonstrated a positive urease breath test and serum H. pylori IgG antibodies. The patient was referred to gastroenterology and treated with appropriate antibiotics. After treatment, esophagogastroduodenoscopy revealed chronic gastritis without evidence of H. pylori infection and his skin showed reticulated hyperpigmented patches without evidence of active inflammatory papules. Although previous reports have associated prurigo pigmentosa to H. Pylori gastritis, this is the first report of H. pylori organisms identified in a skin biopsy of prurigo pigmentosa.

Pagetoid Reticulosis After Radiotherapy of Primary Cutaneous Anaplastic Large-Cell Lymphoma

We describe a 60-year-old man with a history of primary cutaneous anaplastic large cell lymphoma on the chest, who presented with a new scaly red plaque on the same site 11 years after radiation therapy. Histological examination revealed a dense epidermotropic infiltrate of atypical mononuclear cells consistent with pagetoid reticulosis. Immunohistochemistry revealed the infiltrate to be CD4, CD8, and CD30. Remarkably, all the atypical cells were strongly CD30, and furthermore, the CD30 cells were found exclusively in the epidermis. In the initial cutaneous anaplastic large cell lymphoma lesion, the CD4, CD8, and focally CD30 atypical cells were well confined within the dermis with no epidermal component. To our knowledge, the present case seems to be the first description of pagetoid reticulosis presenting at the site of a previously treated dermal anaplastic large cell lymphoma. This case also represents an extreme presentation of epidermotropism and CD30 expression in pagetoid reticulosis.

A Novel Form of Amyloid Deposited at the Site of Enfuvirtide Injection

Cutaneous amyloidosis represents the extracellular deposition of amphophilic hyaline material, which has characteristic staining properties and a fibrillar ultrastructure. The origins of amyloid are diverse; at least 26 amyloid precursor proteins have been described and six have relevance to the skin. While typically of autologous origin, cutaneous amyloidosis has been rarely associated with deposition of medication within the dermis and subcutis.1 Herein, we present a case of cutaneous amyloidosis at the injection site of the antiretroviral medication, enfuvirtide. A 55 year old female who was seropositive for the human immunodeficiency virus (HIV) presented with large, indurated plaques at the sites of subcutaneous enfuvirtide injections on her arms and abdomen (Figure 1). She reported that the sites became ‘‘hot and red’’ after enfuvirtide injections

Appropriate use criteria in dermatopathology: Initial recommendations from the American Society of Dermatopathology

Appropriate use criteria (AUC) provide physicians guidance in test selection, and can affect health care delivery, reimbursement policy and physician decision‐making.

Review of the current medical literature and assessment of current utilization patterns regarding mismatch repair protein immunohistochemistry in cutaneous Muir-Torre syndrome-associated neoplasms

Muir–Torre syndrome is a clinical variant of Lynch syndrome defined by the synchronous or metachronous occurrence of at least one sebaceous neoplasm and at least one Lynch syndrome‐related internal cancer. Although screening guidelines for patients with colorectal carcinomas have been established, screening guidelines for cutaneous Muir–Torre associated neoplasms are not currently available. As such, we reviewed the current evidence for the use of MLH1, MSH2, MSH6 and PMS2 immunohistochemistry when cutaneous Muir–Torre associated neoplasms are encountered. We identified weak to moderate support overall for the global use of these assays, with some evidence suggesting a tailored approach using clinical parameters as an adjunct. We also assessed the current utilization patterns of attendees of the American Society of Dermatopathology Annual Meeting (Chicago, 2016). We found that 91% of respondents utilize mismatch repair immunohistochemistry, with the majority utilizing these tests only when requested by the submitting clinician.

Review of the current medical literature and assessment of current utilization patterns regarding human papillomavirus in situ hybridization and immunohistochemistry in dermatopathology: LITZNERet al .

Human papillomaviruses have been implicated in many cutaneous diseases. Practicing dermatopathologists often consider using immunohistochemistry and in situ hybridization to help clarify the histologic diagnosis, particularly in cases with borderline or nondiagnostic features. We reviewed the current evidence behind the use of these two techniques in dermatopathology. We identified only two studies utilizing the currently available immunohistochemical antibodies. We found more evidence regarding the use of in situ hybridization; however, the majority of this evidence focuses on diagnosing condylomas and other lesions of the genital skin. We also assessed current utilization patterns of attendees of the American Society of Dermatopathology annual meeting (Chicago, 2016) which revealed a wide spectrum of current utilization ranging from no use to regular use more than once per month. Two‐thirds of respondents utilized these tests primarily when requested by the submitting clinician and one‐third of the respondents utilize these tests reflexively in specific clinical scenarios.