Benign Fibromyxoid Lesion of the Breast: A Distinct Entity From Benign Spindle Cell Tumors of the Mammary Stroma?

Myxoid lesions of the breast can be diagnostically challenging entities. We report 4 cases of CD34+ fibromyxoid lesion that have been previously diagnosed as "benign myxoid lesion," "nodular mucinosis," or "mammary myofibroblastoma, myxoid type" on the basis of CD34-positivity. The lesions were microscopically well circumscribed and composed of a paucicellular spindle cell proliferation in a background of myxoid stroma. No epithelial component was identified. The spindle cells showed immunohistochemical reactivity for CD34 and smooth muscle actin. Based on morphologic and immunohistochemical similarities between these cases and myxoid myofibroblastoma, we compared 4 myxoid lesions with cases of typical myofibroblastoma, utilizing retinoblastoma (Rb) antibody and fluorescent in situ hybridization for 13q14 gene rearrangement (encoding the Rb gene). The myxoid lesions showed retention of Rb protein by immunohistochemistry, whereas Rb expression was lost in cases of myofibroblastoma. We identified loss of 13q14 in 3 of 4 cases of myofibroblastoma. Notably, 13q14 gene rearrangement was not observed in any of the myxoid lesions. Our data show that there is at least a subset of CD34+ fibromyxoid lesions that, despite overlapping morphologic and immunohistochemical phenotype and proposed common histogenesis with myofibroblastomas, is genetically distinct from the latter based on Rb analysis.

FROSTED BRANCH ANGIITIS IN METHIMAZOLE-INDUCED ANTINEUTROPHIL CYTOPLASMIC ANTIBODY-POSITIVE VASCULITIS.

PURPOSE: To describe an unusual case of frosted branch angiitis that developed in a patient with acute onset systemic vasculitis possibly triggered by the antithyroid medication methimazole. METHODS: We conducted a thorough review of the medical records of a 16-year-old female patient who presented with frosted branch angiitis. During the initial hospital admission, the patient underwent an extensive systemic workup to determine the etiology of her disease and ophthalmologic testing including fundus photographs and fluorescein angiography. RESULTS: Our patient presented with a unilateral acute onset loss of vision, whose fundus examination revealed the pathognomonic features of frosted branch angiitis. Extensive systemic workup revealed an antineutrophilic cytoplasmic antibody-positive vasculitis, possibly triggered by methimazole. CONCLUSION: This case is the first reported frosted branch angiitis associated with a drug-induced antineutrophilic cytoplasmic antibody-positive vasculitis triggered by methimazole.

Assessing the Relationship of Mammographic Breast Density and Proliferative Breast Disease.

Increased breast density and a history of benign breast biopsy are both considered risk factors for developing breast cancer. Understanding the specifics of these risk factors and their relationship to each other can lead to a better understanding of a patient's propensity for breast cancer development and improved surveillance strategies. We included 245 women who underwent a benign breast biopsy without atypia between October 2011 and June 2013. Biopsies were performed for suspicious calcifications as well as masses and architectural distortion. Lesions biopsied were divided into two groups: calcified and noncalcified lesions. The patient's breast density was assessed on most recent mammogram and was classified using the American College of Radiology BI-RADS density categories. Based on histologic diagnosis, each case was classified as proliferative or nonproliferative breast disease. The median age of the cohort (n = 245) was 55 years (range, 40-84 years). There were 162 (66%) postmenopausal women in the study. A core biopsy was performed for calcifications in 33.5% cases and for noncalcified lesions in 58% cases. In patients with dense breast tissue, an underlying proliferative histology was found significantly more frequently with calcifications (66.7%) as opposed to noncalcified lesions (35.9%) (RR = 2.3 (1.3-4.0); χ(2) = 8.7; p = 0.003). In nondense breast patients, there was no significant difference (RR = 1.1 (0.7-1.8); χ(2) = 0.1; p = 0.738). In the postmenopausal group, women with dense breasts had proliferative histology significantly more frequently than women with nondense breasts (55.3% versus 38.3%; p < 0.05), regardless of the underlying lesion type. Postmenopausal women with dense breasts who underwent a breast biopsy with benign histology had a significantly higher likelihood of having proliferative breast disease, regardless of underlying lesion type. Women with dense breasts also showed proliferative histology significantly more often for calcifications as opposed to noncalcified lesions.

Blue nevus and "malignant blue nevus:" A concise review.

Blue nevi are a heterogeneous group of lesions that can display a variety of different clinicopathological characteristics. Although attempts are made to classify each lesion into defined subtypes, there can be overlap between the subtypes. The clinical and histolopathologic features of common blue nevi and cellular blue nevi are discussed, as well as blue nevi with atypical features and malignant lesions with features of blue nevi.

"Low-Fat" Pseudoangiomatous Spindle Cell Lipoma: A Rare Variant With Loss of 13q14 Region.

Spindle cell and pleomorphic lipoma constitute a spectrum of lipomatous lesions with characteristic clinical, morphologic, immunohistochemical, and molecular features. Multiple variants have been previously described including vascular, fibrous, plexiform, and those with significantly less fat termed "low-fat" and "fat-free" by Folpe. Cytogenetically, spindle cell lipomas frequently display monoallelic loss of 13q14 region, an abnormality also found in cellular angiofibroma and mammary-type myofibroblastoma. Pseudoangiomatous spindle cell lipoma, originally described by Fletcher et al in 1994, is a rare variant within the spindle cell/pleomorphic lipoma spectrum, with less than 20 published cases. It consists of an admixture of spindle cells, "ropey" collagen, variable amounts of mature fat, and irregular, branching slit-like vascular spaces. The authors present a case of a 1-cm subcutaneous lesion excised from the neck of a 70-year-old man with classic histologic and immunohistochemical features of "low-fat" pseudoangiomatous spindle cell lipoma. Fluorescence in situ hybridization demonstrated a loss of 13q14 region, a characteristic presumed cytogenetic finding of spindle cell lipoma, which has been previously unconfirmed in this variant.

Diffuse pulmonary neuroendocrine cell hyperplasia involving the chest wall.

Diffuse pulmonary neuroendocrine cell hyperplasia (DIPNECH) is characterized by a diffuse hypertrophy of neuroendocrine cells along the distal bronchioles. This condition is characterized by obstructive lung physiology and the development of small carcinoid tumors. We present a case of DIPNECH in a patient undergoing surgery for a primary lung adenocarcinoma. Interestingly, the chest wall also demonstrated involvement of DIPNECH indicated by the presence of small carcinoid tumors. The absence of any lung carcinoid tumor greater than 5 mm and the absence of lymph node metastases render the chest wall involvement unlikely to represent metastatic disease.

Adenocarcinoma of the esophagus with signet ring cell features portends a poor prognosis.

BACKGROUND: Adenocarcinoma with signet ring cell (SRC) features has been reported to be a poor prognostic marker in gastric and colorectal carcinomas. Although uncommon in the esophagus, SRC histology, interestingly, has been correlated with improved survival. Our impression has been that the incidence of esophageal adenocarcinomas with SRC features is increasing and is associated with worse outcomes. We hypothesize that patients with SRC histology present with more advanced disease, respond less well to induction therapy, and have decreased survival after resection compared with patients with non-SRC adenocarcinoma. METHODS: The medical records of 151 consecutive patients who underwent resection for adenocarcinoma of the esophagus or gastroesophageal junction in a prospectively maintained database from 1998 to 2011 were reviewed. Outcomes of 23 patients (15%) with SRC histology (21 men, 2 women; average age, 66 years) were compared with 128 patients (85%) with non-SRC adenocarcinoma (116 men, 12 women; average age, 63 years). Overall survival, stage-specific survival, and response to induction therapy were evaluated. Cox regression multivariate analysis was used to identify independent predictors of 3-year survival. RESULTS: SRC and non-SRC patients were evenly matched for clinical and tumor characteristics. Downstaging achieved with induction therapy was 13.3% (2 of 15) in SRC histology patients vs 67.1% (53 of 79) in non-SRC patients (p ≤ 0.001). Patients with SRC histology who did not respond well to induction treatment demonstrated strong trends toward a worse 3-year survival than patients with non-SRC adenocarcinoma (p = 0.084). The overall 3-year survival was 65.6% in patients without SRC histology vs 34.8% in those with SRC (p = 0.006). Patients with pathologic stage II or III and SRC histology had a 3-year survival of 27.3% compared with 57.4% in patients with non-SRC adenocarcinoma (p = 0.01). Multivariate analysis showed SRC histology trended toward significance as an independent risk factor for poor survival (p = 0.060). CONCLUSIONS: Patients with adenocarcinoma of the esophagus or gastroesophageal junction and SRC histology respond less well to induction therapy and have decreased overall survival compared with patients with non-SRC histology.

Hypertrophic discoid lupus erythematosus.

Hypertrophic discoid lupus erythematosus is a distinct form of chronic cutaneous (discoid) lupus, which is characterized by hyperkeratotic plaques that typically are observed over the face, arms, and upper trunk. We present the case of a 43-year-old man with verrucous plaques that were distributed symmetrically over the face, who initially was treated with oral antibiotics and topical glucocorticoids for acne vulgaris. A biopsy specimen confirmed the diagnosis of hypertrophic discoid lupus erythematosus. The clinical and histopathologic features of this clinical variant are reviewed.

Pemphigoid gestationis.

Pemphigoid gestationis is a rare autoimmune blistering disease of pregnancy. It is characterized by pruritic, urticarial plaques with the development of tense vesicles and bullae within the lesions. Pemphigoid gestationis has been associated with premature delivery, small-for-gestational-age infants. Recurrences with subsequent pregnancies are often more severe. Oral glucocorticoids are the mainstay of therapy. Differentiation of pemphigoid gestationis from pruritic urticarial papules and plaques of pregnancy is essential because management and outcomes differ. In instances in which clinical diagnosis is difficult, direct immunofluorescence tests, immunoblots, or ELISA studies of anti-basement-membrane zone antibodies are useful in establishing the diagnosis.

Incontinentia pigmenti.

Incontinentia pigmenti is an X-linked dominant genodermatosis that can affect the teeth, eyes, and central nervous system as well as the skin. We describe an infant girl with characteristic cutaneous findings, which progressed through the vesicular, verrucous, and hyperpigmented stages in the first year of life. During the neonatal period, recognition of the linear distribution of vesicular lesions and associated peripheral eosinophilia as well as leukocytosis (which might suggest an infectious etiology) can help to establish the diagnosis. This enables early initiation of ophthalmologic care, which can help to prevent visual sequelae.

Familial benign chronic pemphigus (Hailey-Hailey disease).

We present an atypical case of familial benign chronic pemphigus (Hailey-Hailey disease) that manifested with relapsing, flaccid vesicles and erosions, which were limited to the upper chest, anterior aspect of the neck, and anterior aspects of the upper arms without intertriginous involvement. Although individual eruptions in this patient demonstrated asymmetry, relapses did not obey a segmental distribution. To the best of our knowledge, no other patient has been described with symmetric lesions that were localized solely to the anterior upper body without a prior history of lesions at commonly affected disease sites, which include skin folds, the back, and the posterior and lateral aspects of the neck. This unusual presentation of Hailey-Hailey disease highlights the variable nature of the disease.

Atypical mycobacteria infection in an immunocompromised patient.

A 61-year-old woman with systemic lupus erythematosus and Sjögren syndrome presented with a two-month history of symptomatic nodules on the buttocks and thighs that progressed to involve the dorsal aspects of the hands. On examination, infiltrative papules, nodules, and plaques were present in these regions. Biopsy specimens demonstrated granulomatous inflammation and acid-fast bacilli with the use of a Fite stain, although a culture and polymerase chain reaction analysis were negative. The patient continues to improve on long-term clarithromycin therapy. Atypical mycobacterial infections are becoming more common, especially in immunocompromised patients. Antimicrobial therapy, either with a single agent or multiple agents, often is prolonged. A high index of suspicion is warranted in immunocompromised patients, which includes those with connective-tissue diseases that are active or that require immunosuppression. In these patients, the differential diagnosis includes infectious as well as inflammatory, reactive, or neoplastic processes.

MASH1: a useful marker in differentiating pulmonary small cell carcinoma from Merkel cell carcinoma.

Merkel cell carcinoma is the cutaneous counterpart of small cell carcinoma, and the most important differential diagnosis is cutaneous metastasis of small cell carcinoma of the lung. There have been a handful of studies reporting on the utility of a variety of immunohistochemical markers that distinguish between the two entities. Achaete-scute complex-like 1 (MASH1, ASCL1) is important in the development of the brain and the diffuse neuroendocrine system including pulmonary neuroendocrine cells. A recent study, using a cDNA array, identified Mash1 as one of the best classifier genes to differentiate pulmonary small cell carcinoma from Merkel cell carcinoma. We immunohistochemically applied this finding to the diagnostic setting. A total of 30 cases of Merkel cell carcinoma and 59 cases of small cell carcinoma of the lung were immunostained with anti-MASH1 and TTF-1 antibodies. Of 59 small cell carcinomas, 49 (83%) expressed MASH1 in nuclear staining whereas out of 59 small cell carcinomas, 43 (73%) expressed TTF-1 in nuclear staining. MASH1 was completely negative in all 30 Merkel cell carcinomas whereas TTF-1 expression was seen in 1 of the 30 Merkel cell carcinomas (3%). MASH1 is a useful adjunct marker for differentiating small cell carcinoma of the lung from Merkel cell carcinoma.