Do Not Skip the Retroflexion: A Case of Disseminated Anorectal Mucosal Melanoma.

Less than 4% of melanomas are of mucosal origin, with primary anorectal mucosal melanomas comprising a small subset. Mucosal melanomas are often diagnosed at an advanced stage due to delay in patient presentation and obscured tumor origins leading to a more aggressive behavior and less favorable prognosis when compared with cutaneous melanomas. We present a case of metastatic anorectal mucosal melanoma with a negative colonoscopy 1 year earlier.

Cytopathology milestones: can you get to level 5?

INTRODUCTION: ACGME Milestones describe 6 areas of proficiency, indicating readiness for practice. Each is divided into 5 levels of mastery; Level 1 (new trainees) through Levels 4 (graduation) and 5 (aspirational). Milestones reporting began Spring 2016. We used Milestones to assess graduated fellows. MATERIALS AND METHODS: We conducted phone interviews with previous fellows and collected demographic information including practice setting. We asked graduates if they fulfilled each example of mastery and recorded their answers. RESULTS: A total of 22 fellows graduated from 2010 to 2017; 15 responded (10 academic, 5 private). Milestones in which nearly all respondents performed well (Level 4+) were: PC1, MK1, SBP2, SBP4, PROF1-4, ICS1-3. Some were more challenging (PC2, MK2, SBP1/3/5, PBL1). For PC2, 2 respondents achieved Level 1 (did not perform fine-needle aspirations). For MK2, 2 respondents achieved Level 1 (did not evaluate Papanicolaou). For SBP1, 80% in private practice achieved Level 5; 50% in academics achieved Level 3. For SBP3, 80% in private practice achieved Level 4+; 100% in academics achieved maximum Level 2. For SBP5, 60% of all respondents achieved maximum Level 3; only 1 achieved Level 5. CONCLUSIONS: Many Milestones are attainable. Eleven of 18 yielded Level 4+ from most respondents. Three (PC2, MK1, MK2) yielded rare Level 1 due to scope of practice. Others (SBP1, SBP3) reflect more of an all-or-nothing phenomenon. For SBP5, most respondents achieved Level 3; only 1 achieved Level 5. Some Milestones are highly dependent on practice setting, and others remain aspirational.

Mammary Extranodal Rosai-Dorfman Disease With and Without Associated Axillary Lymphadenopathy: Insights for Practitioners of Breast Pathology.

Rosai-Dorfman disease is a rare proliferative histiocytic disorder of lymph nodes that is descriptively known as sinus histiocytosis with massive lymphadenopathy. Extranodal involvement of the parenchyma of the breast is uncommonly reported, with fewer than 50 cases of mammary extranodal disease detailed in the English-language literature. We characterize a retrospective series of adult female patients from a single institution with Rosai-Dorfman disease of the breast and axillary lymph nodes. Because Rosai-Dorfman disease of the breast and axillary lymph nodes may clinically, radiographically, and histologically mimic breast carcinoma and other conditions, we present an illustrated review of the disease and its relevant differential diagnoses in hopes of raising awareness and allowing for accurate management of affected patients.

Androgen Receptors in Resected Ductal Carcinoma In Situ of Breast: Novel Insights With Possible Implications for Testing and Targeted Endocrine Chemoprevention Trials.

Mammary ductal carcinoma in situ (DCIS) is classically treated by combinations of excision, radiation, and endocrine therapy, based upon the specific needs of individual patients. Estrogen receptor (ER) status is generally assessed by immunohistochemistry (IHC) in newly diagnosed cases of DCIS, and endocrine therapy in this setting is thought to be chemopreventive. The potential impact of androgens on mammary carcinogenesis has been studied in recent years, and several authors have proposed androgen receptor (AR) IHC testing and targeted antiandrogenic therapy in patients with locally advanced or metastatic triple-negative invasive breast cancer (ie, negative for ER and progesterone receptor and HER-2). Very little has been published on AR in DCIS. We report results of AR IHC on archival tissue blocks from 221 adult female patients, each of whom underwent definitive breast resection of DCIS. Of the 221 cases, 72 (33%) were shown to express AR in their DCIS at or above the 10% threshold often used for invasive carcinoma. AR expression was seen in all grades of DCIS. Of the 72 positive AR cases, 21 (29%) were ER negative, corresponding to 10% (21/221) of all patients. The majority of the AR-positive cases were high grade, and the most common histologic subtype in this subset was a solid growth pattern with apocrine features. Early data from clinical trials evaluating AR antagonists in invasive/metastatic triple-negative breast cancer suggest that some patients may benefit from androgen blockade. IHC testing and potential clinical trials of AR antagonists for chemoprevention in patients with AR-positive and ER-negative DCIS could be considered.

Mammary mesenchymal and fibroepithelial lesions: An illustrated cytomorphologic update with differential diagnoses.

The Uniform Approach to Breast Fine Needle Aspiration Biopsy was put forward by a learned group of breast physicians in 1997. This landmark manuscript focused predominantly on diagnosis and reporting of mammary epithelial lesions. Today, most American practitioners turn initially to core biopsy rather than aspiration biopsy for the first line diagnosis of solid breast lesions; however, recent efforts from the International Academy of Cytology have produced a system called the Standardized Reporting of Breast Fine Needle Aspiration Biopsy Cytology (colloquially labeled in 2017 as the "Yokohama System"), suggesting a new interest in breast fine needle aspiration (FNA), especially in resource limited settings or clinical practice settings with experienced breast cytopathologists. Fibroepithelial lesions of the breast comprise a heterogeneous group of biphasic tumors with epithelial and stromal elements. Mesenchymal lesions of the breast include a variety of neoplasms of fibroblastic, myofibroblastic, endothelial, neural, adipocytic, muscular, and osteo-cartilaginous derivations. The cytology of mesenchymal breast lesions is infrequently described in the literature and is mainly limited to case reports and small series. This illustrated review highlights the cytologic features of fibroepithelial and mesenchymal mammary proliferations and discusses differential diagnoses and histomorphologic correlates.

"Triple hit" lymphomas: A retrospective cytology case series of an uncommon high grade B-cell malignancy with C-MYC, BCL-2 and BCL-6 rearrangements.

The Revised fourth Edition World Health Organization (WHO) Classification of Tumors of Hematopoietic and Lymphoid Tissues suggests novel categories, including "high grade B-cell lymphoma with MYC and BCL2 and BCL6 gene rearrangements." These diseases are known colloquially as "double hit" and "triple hit" lymphomas. The "first-hit" in these cases is the harboring of a MYC rearrangement. Concurrent derangements of BCL2 and BCL6 can be the "second-hit" or "third-hit." To our knowledge, this is the first report of "triple-hit" lymphomas in cytology specimens. The files of the Cleveland Clinic (January 2007 through December 2017) were searched for all "triple hit" lymphomas. Four cases met inclusion criteria (cytology slides in files and histologically confirmed "triple hit" lymphoma). All slides were reviewed. The mean age was 65 years, with a male predominance. All patients presented at advanced stage and showed progressive disease despite therapy. FISH studies (histologic sections) confirmed translocations of MYC (8q24), BCL2 (18q21) and BCL6 (3q27) in all patients. All cases were characterized by high cellularity, dispersed cells, presence of stripped nuclei, lymphoglandular bodies, apoptotic bodies, cytomegaly, nucleomegaly, nuclear envelope irregularities, macronucleoli (most often single), recognizable mitoses and presence of cytoplasmic vacuoles (variable). The WHO recommends that all large B-cell lymphomas be investigated using cytogenetic or molecular techniques. Concurrent inhibition of MYC and BCL2 is a potentially effective treatment strategy for triple hit lymphomas, and an expanding literature exists regarding predictive biomarkers and therapeutic regimens. It is our intention to raise awareness of this uncommon mature B-cell neoplasm within the cytodiagnostic community.

The incidence of celiac disease antibodies in plasma specimens with low hemoglobin levels.

Antibodies to gliadin and tissue transglutaminase (TTG) are associated with celiac disease. Celiac patients often present with low hemoglobin levels; however, the incidence of celiac disease in patients with low hemoglobin levels is unknown. We investigated the incidence of celiac disease-associated antibodies in plasma obtained from individuals with low and normal hemoglobin levels. Our objective was to determine if antigliadin and anti-TTG antibodies are more prevalent in individuals with low hemoglobin levels than in control subjects with normal hemoglobin levels. Following IRB approval, we obtained 86 plasma specimens with hemoglobin levels less than or equal to 10 g/dL and 88 plasma specimens from individuals with hemoglobin levels greater than or equal to 13 g/dL. IgA and IgG antibodies to gliadin and TTG were determined by ELISA assays provided by BioRad, Inc. IgG antigliadin Ab was present in 6 out of 86 low hemoglobin specimens and in two of the normal hemoglobin specimens. The IgA antigliadin ELISA assay was positive in 19 out of 86 low hemoglobin specimens and in 21 out of 88 normal hemoglobin specimens. IgA anti-TTG was detected in 9 out of 86 low hemoglobin specimens and in 3 out of 88 normal hemoglobin specimens. IgG anti-TTG was not present in any of the specimens. IgA antibodies to TTG were more prevalent in individuals with low hemoglobin levels. The incidence of IgG anti-TTG and IgG and IgA antibodies to gliadin was not related to plasma hemoglobin levels in our sample.