Inflammation markers on benign breast biopsy are associated with risk of invasive breast cancer in African American women.

PURPOSE: Markers of inflammation, including crown-like structures of the breast (CLS-B) and infiltrating lymphocytes (IL), have been identified in breast tissue and associated with increased risk of breast cancer (BrCa), however most of this work has been performed in primarily non-Hispanic white women. Here, we examined whether CLS-B and IL are associated with invasive BrCa in African American (AA) women. METHODS: We assessed breast biopsies from three 5-year age-matched groups: BrCa-free AA women (50 Volunteer) from the Komen Normal Tissue Bank (KTB) and AA women with a clinically-indicated biopsy diagnosed with benign breast disease (BBD) from our Detroit cohort who developed BrCa (55 BBD-cancer) or did not develop BrCa (47 BBD only, year of biopsy matched to BBD-cancer). Mean adipocyte diameter and total adipose area were estimated from digital images using the Adiposoft plugin from ImageJ. Associations between CLS-B, IL, and BrCa among KTB and Detroit biopsies were assessed using multivariable multinomial and conditional logistic regression models. RESULTS: Among all biopsies, Volunteer and BBD only biopsies did not harbor CLS-B or IL at significantly different rates after adjusting for logarithm of adipocyte area, adipocyte diameter, and BMI. Among clinically-indicated BBD biopsies, BBD-cancer biopsies were more likely to exhibit CLS-B (odds ratio (OR) = 3.36, 95% Confidence Interval (CI): 1.33-8.48) or IL (OR = 4.95, 95% CI 1.76-13.9) than BBD only biopsies after adjusting for total adipocyte area, adipocyte diameter, proliferative disease, and BMI. CONCLUSIONS: CLS-B and IL may serve as histological markers of BrCa risk in benign breast biopsies from AA women.

"Pigmented Extramammary Paget Disease"-A Potential Mimicker of Malignant Melanoma and a Pitfall in Diagnosis: A Case Report and Review of the Literature.

Extramammary Paget disease (EMPD) is a rare intraepithelial carcinoma and an uncommon variant of Paget disease affecting areas of the apocrine-rich skin of the perineum, vulva, and less commonly, axilla. Women in their sixth to eighth decades are commonly affected. It is exceedingly rare for EMPD to present on the face, chest, abdomen, or other nonapocrine sites and even more unusual for EMPD to present as a pigmented lesion. The relationship between Paget cells in pigmented extramammary Paget disease (PEMPD) and reactive proliferation and colonization by melanocytes has been poorly explored. The relevance of this rare entity resides in its potential to be misdiagnosed clinically and histopathologically as malignant melanoma in situ. Therefore, application of a panel of immunostains and careful analysis and interpretation of these findings are essential to arrive at the correct diagnosis. We report a new case of PEMPD on a nonapocrine site. The specimen was examined by routine microscopy including hematoxylin and eosin stain as well as immunostains. Histologic examination revealed characteristic features of PEMPD confirmed with immunohistochemical stains.

Eosinophilic Dermatosis of Myeloproliferative Disease in a Young Adult With Diffuse Large B-Cell Lymphoma.

Exaggerated insect bite reactions present as exuberant papular and vesiculobullous lesions in patients with hematologic malignant neoplasms. The most commonly reported hematological malignancy with exaggerated insect bite reactions is chronic lymphocytic leukemia. Other reported reactions have been seen in patients with mantle cell lymphoma. Clinical presentation may vary with many patients unaware of a previous insect bite. Therefore, the terms "exaggerated bite-like reaction" and "eosinophilic dermatosis of myeloproliferative disease" have been proposed. The lesions may wax and wane or persist for many years, and they seem to be unrelated to the underlying hematologic disorder course or therapy. In some circumstances, the lesions may actually precede the diagnosis of the hematological malignancy. In this study, we describe a case of "eosinophilic eruption of myeloproliferative disease" associated with diffuse large B-cell lymphoma in a young adult. To the best of our knowledge, this is the first case reported in association with diffuse large B-cell lymphoma.

Langerhans Cell Histiocytosis Associated With Underlying Hematolymphoid Disorders in Adults: Report of 2 Cases and Review of the Literature.

Langerhans cell histiocytosis (LCH) is an uncommon disorder characterized by proliferation of abnormal LCs usually affecting children and adolescents. LCH in adults first presenting in the skin is rare. Although LCH and even LCH with a second malignancy may be more common in children, cutaneous LCH with a second hematologic malignancy has been more commonly identified in adults. The authors report 2 new cases of LCH in adult patients with underlying myelodysplasia and follicular lymphoma. The specimens were examined by routine microscopy and immunohistochemical stains for S100 protein and CD1a. Patients were elderly men with established diagnoses of follicular lymphoma and myelodysplasia, presented with follicular lesions and erythematous plaques involving intertriginous areas. Histologic examination revealed collections of mononuclear cells in upper dermis, which demonstrated strong positivity for S100 and CD1a, confirming their identity as LCs. BRAF analysis returned negative for detection of BRAF V600E mutation in both patients. The authors have recently encountered 2 cases of adult patients with skin-limited LCH predated by other lymphoproliferative disorders. The association between LCH and hematopoietic disorders may be explained by a common bone marrow precursor that is differentiating along different cell lines. Cutaneous LCH may be associated with underlying lymphoproliferative disorders and should be considered in the differential diagnosis of cutaneous eruptions in patients with hematopoietic disorders. Clinical follow-up evaluation of patients diagnosed with LCH for peripheral blood abnormalities and lymphadenopathy or "B symptoms" may be prudent in patients not already carrying a diagnosis of an underlying hematologic disorder.

An Update Regarding the Molecular Genetics of Melanocytic Neoplasms and the Current Applications of Molecular Genetic Technologies in Their Diagnosis and Treatment.

Molecular genetic technologies are used to aid in diagnosis and treatment of borderline melanocytic tumors as an adjuvant to the gold standard histopathologic evaluation. A specific set of fluorescence in situ hybridization probes is widely used to aid in diagnosing challenging melanocytic lesions. New melanoma probe cocktails have revealed increased sensitivity and specificity in ambiguous melanocytic cases. Array comparative genomic hybridization is a more complex technology used for the work-up of diagnostically problematic Spitzoid melanocytic proliferations. Cutting-edge technologies, including next-generation sequencing and cell-free nucleic acid analysis, are promising biomarker applications for mutation detection towards personalized patient management.

New variant lymphomatoid papulosis type E preceding and coexisting with mycosis fungoides - a case report and review of the literature.

Angioinvasive (type E) lymphomatoid papulosis (LyP) is a recently described subtype of LyP presenting with eschar-like lesions that can be mistaken for aggressive forms of angiocentric cutaneous T-cell lymphoma. None of the cases of angioinvasive LyP described thus far have been associated with mycosis fungoides (MF). Herein, we describe a case of angioinvasive LyP type E coexisting with MF. The patient presented with an eschar on his chest and over time developed new nodules and large plaques with eschar formation, all of which resolved spontaneously over a period of a few weeks without intentional therapy. Biopsy revealed a CD30+ atypical inflammatory cell infiltrate with marked angiocentricity. Later, he developed erythematous annular scaly patches histologically consistent with MF. Our patient's clinical course confirms the indolent behavior characteristic of LyP despite the aggressive clinical and histologic appearance of lesions. The co-occurrence of angioinvasive LyP and MF in our patient highlights the propensity for LyP type E to coexist with MF, as is characteristic of other LyP subtypes, and supports the theory that LyP and MF are related T-cell lymphoproliferative disorders. Patients with LyP can present with large lesions exhibiting eschar formation and an atypical angiocentric/angiodestructive lymphoid infiltrate and should be spared overtreatment.

Werner syndrome in an Iranian family.

A 49-year-old man was first seen in our department for the evaluation of scleroderma-like skin changes and a nonhealing ulcer on his leg from years before referral. His medical history was of long duration. His growth was stunted at the age of 12. At 21 years of age, the patient noted graying of the scalp hair, most prominent on his temples, and the process was progressively completed by the age of 23. At the same age, atrophy and thinning of the skin and loss of subcutaneous fat resulted in a tense, shining, and adherent appearance of his skin, most obvious on his face and extremities. Soon after, he developed a high-pitched, hoarse voice. He had undergone bilateral cataract surgery at the age of 30. Around the age of 46, he developed a unilateral nonhealing chronic leg ulcer (Figure 1). He had separated from his wife because of infertility. He was the first offspring of his second-degree healthy relative parents. The other 3 siblings had similar signs and symptoms. Our patient gave the history of premature graying of the hair of his younger brother at the age of 18 and his 2 younger sisters at the age of 12 and 16. His brother had recently received diagnoses of bilateral cataract and diabetes mellitus. All of the siblings had ceased growth from early adolescence. On physical examination, our patient's weight was 48 kg and his height was 150 cm. He had normal intelligence. He was speaking with a high-pitched and childish voice. He had a bird-like appearance with a beak-shaped nose. Mottled and diffuse pigmentation and poikiloderma appearance was conspicuous on his neck (Figure 2). The entire skin was smooth, shiny, and scleroderma-like, and a marked decrease in the subcutaneous fat was noted over the extremities. A deep cutaneous ulcer was evident on his slimmed leg. Digital ulcers were not found, and radial and dorsalis pedis pulses were palpable. Clinodactyly of the toes were conspicuous. His nails were dystrophic and he had used dentures from the age of 20. On examination of the external genitalia, his testes were smaller than normal. In the biopsy taken from the leg ulcer, there were no signs of malignancy. There were no signs ofosteomyelitis on x-ray. Biopsy of the normal skin revealed atrophic epidermis and thick dermis with hyalinization of the collagen fibers and absence of pilosebaceous structures (Figure 3). The patient's scalp hair was thin and sparse and there were few axillary and pubic hairs. His fasting plasma glucose level was normal.

Ectodermal dysplasia with alopecia, onychodysplasia, hypohidrosis, keratoderma, abnormal teeth and deafness.

The ectodermal dysplasias are a heterogeneous group of disorders with primary defect in hair, teeth, nail and sweat gland function. Numerous types have been described and several classifications exist. Here, we present a patient with ectodermal dysplasia with alopecia, dysplastic nails, hypohidrosis, sensorineural deafness, palmoplantar keratoderma, abnormal teeth and dry skin. To our knowledge, combination of all these features in ectodermal dysplasia has not been reported in the past. The etiology is unknown, but consanguinity of parents points to an autosomal recessive inheritance.