Significance of flat epithelial atypia on mammotome core needle biopsy: Should it be excised?

The aim of this study was to determine the morphologic types, associations, and significance of flat epithelial atypia (FEA) with or without atypical ductal hyperplasia (ADH) in mammotome core needle biopsies. We evaluated the correlation of FEA in core biopsies with follow-up excision biopsies to predict the likelihood of upgrade to carcinoma. We also investigated the utility of Ki-67 in predicting which lesions were associated with carcinoma in the excisional biopsies. Core biopsies with a diagnosis of atypia were categorized as pure FEA, pure ADH, or both. The following parameters were recorded: indication for core biopsies, presence of microcalcifications, inflammation, and stromal changes. A total of 60 core biopsies from 56 patients were studied. Pure ADH, pure FEA, and concomitant FEA and ADH were seen in 13%, 23%, and 64% of core biopsies, respectively. The most common architectural pattern of FEA resembled blunt duct adenosis (52%), followed by cystically dilated ducts with secretions (38%) and apocrine features (10%). Chronic inflammation and stromal changes were noted in 29% and 36% of FEA, respectively. Excisional biopsies in 48 of 56 patients demonstrated ductal carcinoma in situ and/or invasive carcinoma in 10 patients (21%), lobular carcinoma in situ or atypical lobular hyperplasia in 5 (11%), residual ADH in 11 (23%), and no atypia in 24 patients (50%). Three (21%) of 14 pure FEA upgraded to ductal carcinoma in situ and/or invasive carcinoma on excisional biopsy. The staining for Ki-67 in FEA/ADH was similar regardless of whether they were upgraded to carcinoma or not. In summary, we found a strong association between FEA and ADH, which may reflect a biologic progression. Most FEAs have a low-power appearance of a well-circumscribed group of ducts. Chronic inflammation and stromal changes are present in a subset of cases. Flat epithelial atypia shows a risk of upgrade to carcinoma similar to that of ADH and, hence, should be recognized and warrants a follow-up excision.     

Calcifications in a clear cell mucoepidermoid carcinoma: a case report with histological and immunohistochemical findings

The aim of this study was to report an unusual case of mucoepidermoid carcinoma (MEC) in a 39-year-old woman. The tumor showed a prominent population of clear and intermediate basal cells. Clear cells rarely predominate over other cell types. Such cases are called clear cell variant of MEC. The case also revealed a variable amount of calcified material in the tumor mass. Calcifications are rare in clear cell MEC. These structures were periodic acid-Schiff positive and diastase resistant, excluding glycogen origin. Immunohistochemistry was performed, and the epidermoid component was positive for cytokeratin (CK)7, CK13, CK14, and CK19. The mucous and clear cells presented mild staining for CK7. Cytokeratins 7, 13, and 19 stained luminal cells, and intermediate cells exhibited positivity for CK7, CK14, and vimentin. The origin of the calcifications is speculated to be the result of dystrophic calcification of the amorphous eosinophilic material secreted by intermediate basal cells.     

Endocrine Dysfunction in Children with Zika-Related Microcephaly Who Were Born during the 2015 Epidemic in the State of Pernambuco,Brazil

Congenital viral infections and the occurrence of septo-optic dysplasia, which is a combination of optic nerve hypoplasia, abnormal formation of structures along the midline of the brain, and pituitary hypofunction, support the biological plausibility of endocrine dysfunction in Zika-related microcephaly. In this case series we ascertained the presence and describe endocrine dysfunction in 30 children with severe Zika-related microcephaly from the MERG Pediatric Cohort, referred for endocrinological evaluation between February and August 2019. Of the 30 children, 97% had severe microcephaly. The average age at the endocrinological consultation was 41 months and 53% were female. The most frequently observed endocrine dysfunctions comprised short stature, hypothyroidism, obesity and variants early puberty. These dysfunctions occurred alone 57% or in combination 43%. We found optic nerve hypoplasia (6/21) and corpus callosum hypoplasia (20/21). Seizure crises were reported in 86% of the children. The most common—and clinically important—endocrine dysfunctions were pubertal dysfunctions, thyroid disease, growth impairment, and obesity. These dysfunctions require careful monitoring and signal the need for endocrinological evaluation in children with Zika-related microcephaly, in order to make early diagnoses and implement appropriate treatment when necessary.     

A Quantitative Approach to SIV Functional Latency in Brain Macrophages

Journal of Neuroimmune Pharmacology - Lentiviruses are retroviruses that primarily infect myeloid cells, leading to acute inflammatory infections in many tissues particularly, lung, joints and the...     

Acellular pertussis vaccine based on outer membrane vesicles capable of conferring both long-lasting immunity and protection against different strain genotypes

Despite high vaccination coverage rates, pertussis continues to be a global concern, with increased incidence widely noted. The current pertussis epidemiologic situation has been mainly attributed to waning immunity and pathogen adaptation. To improve the disease control, a new generation of vaccines capable to overcome those weaknesses associated to the current vaccines need to be developed. Previously we have demonstrated that the outer membrane vesicles obtained from the recombinant Bordetella pertussis strain expressing PagL enzyme (OMVs_BpPagL) are good vaccine candidates to protect against pertussis. In this work the OMVs_BpPagL formulated with diphtheria and tetanus toxoids (Tdap_OMVsBpPagL) was used to evaluate its capacity to offer protection against Argentinean clinical isolates and to induce long-term immunity. To these aims BALB/c mice were immunized with Tdap_OMVsBpPagL and challenged with sublethal doses of the clinical isolate Bp106 selected as a representative circulating isolate. Comparisons with a current commercial Tdap vaccine used at a dose in which pertussis toxin level was equivalent to that of Tdap_OMVsBpPagL were performed. With the normalized doses of both vaccines we observed that Tdap_OMVsBpPagL protected against the clinical isolate infection, whereas current commercial Tdap vaccine showed little protection against such pathogen. Regarding long-term immunity we observed that the Tdap_OMVsBpPagL protective capacity against the recommended WHO reference strain persisted at least 9 months. In agreement with these results Tdap_OMVsBpPagL induced Th1 and Th2 immune response. In contrast, commercial Tdap induced Th2 but weak Th1 responses. All results presented here showed that Tdap_OMVsBpPagL is an interesting formulation to be considered for the development of novel acellular multi-antigen vaccine.     

Dietary and nutraceutical approach to type 2 diabetes

Nutritional medical treatment is the first step to achieve adequate glycemic control and prevent diabetic complications. Lifestyle changes include moderate weight loss (7%) and regular physical activity (150 min/week). The appropriate diet composition is < 30% total fat, < 10% saturated fats, > 15 g/1000 kcal fiber, half soluble, 45–60% of carbohydrates with amoderate intake of sugar (50 g/day) and protein intake of 15–20% of the total calories a day. Patients need to limit the intake of saturated fats to < 7% of the daily calorie intake. Monounsaturated fatty acids such as olive oil and other vegetable oils are recommended. L-carnitine, α-lipoic acid, berberine and ω-3 fatty acids can be useful supplements.     

Cytomorphology of intraductal oncocytic papillary neoplasm of the liver

We describe the first cytology case report of an intraductal oncocytic papillary neoplasm (IOPN) of the liver. A 51‐year‐old male presented with recurrent cholangitis. Magnetic resonance imaging and endoscopic retrograde cholangiopancreatogram revealed a 1.1 × 0.9 cm polypoid lesion within the left intrahepatic bile duct. Fine‐needle aspiration and needle core biopsy (NCB) revealed nests, 3‐dimensional or papillary clusters of columnar or cuboidal cells with loss of polarity. The nuclei were uniform with even chromatin, and cytoplasm was granular or vacuolated. No mitosis or necrosis was seen. The cytologic and histologic diagnosis was “consistent with Intraductal Oncocytic Papillary Neoplasm (IOPN), intermediate grade (borderline).” The patient then underwent a left lateral liver segmentectomy. Microscopic examination showed histology similar to the NCB with no stromal invasion identified. Hepatic IOPN poses a diagnostic challenge due to its broad differential diagnoses. Both malignant and non‐malignant IOPNs may present with similar clinical symptoms, pathology, histology, cytomorphology, and immunohistochemistry. Hepatic IOPN should be excised as it is a precursor lesion of adenocarcinoma. Diagn. Cytopathol. 2014;42:895–898. © 2013 Wiley Periodicals, Inc.     

Irinotecan-eluting stents inhibited neointimal proliferation in hypercholesterolemic rabbit aortas.

OBJECTIVE: To assess the effect of irinotecan-eluting stents (IS) on neointimal growth in the aortas of hypercholesterolemic rabbits and to determine other local histopathological effects such as necrosis, fibrin, and inflammatory reaction. METHODS: Phosphorylcholine-coated stents were deployed in the aortas of hypercholesterolemic rabbits. Group 1 (control; n = 8) received unloaded stents, group 2 (n = 7) and group 3 (n = 9) received IS with 0.046 mg and 1.29 mg of irinotecan, respectively. Eight weeks after implantation the rabbits were killed. Neointimal thickness (NT) was assessed by morphometry. Semiquantitative injury score (from 0 to 3+) was used to analyze inflammatory infiltrate, fibrin deposits, and necrosis in the stented segments. RESULTS: NT was reduced only in high-doses IS (G1, 167.4 +/- 20.8 mu; G2, 170.24 +/- 21.2 mu; G3, 111.56 +/- 12.7 mu; P < 0.05, G3 vs G1 and G2). Necrosis decreased significantly with IS [1.00 +/- 0.10 in G1 to 0.33 +/- 0.07 and 0.02 +/- 0.01 in G2 and G3, respectively] only in the media layer. The inflammatory infiltrate was present in the three layers of aortas from G1, but only decreased significantly in the intimae layer of the high-dose group [1.50 +/- 0.15 in G1 vs 1.00 +/- 0.18 in G3, P < 0.05]. CONCLUSION: Stents loaded with high-dose irinotecan inhibit NT in the aortas of hypercholesterolemic rabbits. This effect was accompanied by decreased inflammatory infiltrate and media necrosis.