A SOX10+/AR- immunoprofile may identify a subset of low positive ER carcinomas with a wider range of ER expression.

BACKGROUND: Invasive breast carcinomas (IBC) that strongly express SOX10 are almost always negative for androgen receptor (AR). Furthermore, this SOX10+/AR- subset of IBC is nearly always estrogen receptor and progesterone receptor negative (ER-/PR-), being most commonly seen in triple negative breast carcinomas (TNBC), but also in a small subset of HER2+/ER-/PR- IBC. Following our previous work demonstrating the expression of SOX10 in a subset of IBC with "low positive" ER expression (i.e. 1-10 % ER+ staining based on CAP guidelines, here referred to as "ER-low"), we sought to investigate the expression of both SOX10 and AR in a larger cohort of ER-low tumors. As our previous work also revealed occasional SOX10 expression in IBC with >10 % ER+ staining, we also included tumors with any percentage of ER staining, as long as the staining intensity was weak (this subset is referred to as "ER-weak"). METHODS: We screened cases of HER2-/ER+ IBC diagnosed at our institution over a 10 year period, identified both ER-low and ER-weak tumors and stained both groups with SOX10 and AR. RESULTS: Strong SOX10 expression was seen in 12/25 (48 %) ER-low tumors and 13/24 (54 %) ER-weak tumors. ER staining in the SOX10+ subset of ER-weak tumors ranged from 15 %-80 % (median 25 %). As expected, AR was negative in all but 1 of the SOX10+ tumors in both groups. While case numbers in these groups were too small for a meaningful statistical analysis, we did note that all SOX10+/AR- tumors within both the ER-low and ER-weak groups were histologic grade 3. CONCLUSION: The presence of a SOX10+/AR- profile in a significant subset of ER-low tumors confirms the findings of our previous work and provides further support for the proposed functionally ER negative status of this group. Furthermore, the fact that the same SOX10+/AR- profile is seen in a roughly equal subset of ER-weak tumors suggests that a wider range of ER staining may be acceptable as "low positive" in SOX10+/AR- tumors, as long as the ER staining is of weak intensity. However, given the small number of cases in this single institution study, we emphasize the need for larger studies to establish the biological and clinical significance of this tumor subset.

A novel and improved selective media for the isolation and enumeration of Klebsiella species.

Bacterial pathogens are fostered in and transmitted through wastewater. Hence, monitoring their impact on sanitation and hygiene is imperative. As part of the monitoring process, culture-based methodologies are primarily used, which centre on the use of selective and differential media. Media available today are, at best, difficult to formulate and, at worst, prohibitively expensive. To address this lacuna, the study proposes a selective and differential medium for Klebsiella spp. Klebsiella blue agar (KBA) is completely selective against selected gram-positive bacteria (Bacillus spp., Staphylococcus aureus) and a few gram-negative bacteria (Acinetobacter baumanii, Serratia marcescens). On the other hand, it supports the growth of the chosen members of the Klebsiella pneumoniae species-complex with a characteristic green colouration. Methylene blue, tryptophan, and bile salt make up the selective components of KBA. Moreover, methylene blue, 0.6% NaCl, and glycerol render it differential. KBA was more selective than HiCrome™ Klebsiella Selective Agar Base (KSA) in replica plating experiments. KBA promoted only 157 CFUs against 209 CFUs in KSA when stamped with 253 CFUs grown on LB. The colonies so isolated were predominantly Klebsiella spp., on identification through colony polymerase chain reaction. Moreover, the differential nature of KBA distinguished Klebsiella aerogenes from other species. On the contrary, KSA lodged colonies indistinguishable from each other and Klebsiella spp. Due to its ease of formulation, high selectivity, differential nature, and cost-effective composition, KBA is a viable option for the routine culture of Klebsiella spp. in environmental and clinical settings. KEY POINTS: • Formulated a novel selective and differential media for Klebsiella spp., named Klebsiella Blue agar • Facile formulation methodology • Can be employed to isolate Klebsiella spp. from complex sources such as wastewater.

Cyto-histo correlation and false-negative urine: Before and after the Paris system for reporting urinary cytology.

BACKGROUND: The impact of implementing the Paris system (TPS) on the rate of discrepant cases in the negative for high-grade urothelial carcinoma (NHGUC) category that had a subsequent diagnosis of high-grade urothelial carcinoma (HGUC) on histology is not well studied. METHODS: We adopted TPS in May 2019. We searched discrepant cases with negative urine cytology 2017-2019 in our cyto-histo correlation database. The urine cytology and follow-up biopsy/resection were reviewed by a cytopathologist who also did Genitourinary (GU) Pathology subspecialty sign-out. Voided urine and instrumented urine were included in this study. RESULTS: There were total of 70 discrepant cases with negative cytology interpretation but HGUC on the subsequent biopsy or resected specimen. Following the TPS criteria, the rate of discrepant negative cytology cases increased from 6 cases between January 2017 and May 2019 to 64 cases after May 2019 when we adopted TPS. There were 2 discrepant negative cases in 2017, 3 cases in 2018, and 65 cases in 2019. Out of 65 cases in 2019, 64 cases were identified after May 2019. Additional 55 urine cytology slides were reviewed according to the TPS criteria, of which, the diagnoses remained unchanged in 45 (82%) cases and 10 (19%) cases were reassigned to either atypical or suspicious categories. The discrepancy was noted more on the instrumented urine and the upper tract urine. However, the false-negative rate rose faster in voided urine and lower tract urine. The risk of HGUC with the category of NHGUC was 0.03% in 2017, 0.05% in 2018, and 1.06% in 2019 at our institution. The increase in false-negative rate could not be attributed to a single cytopathologist. CONCLUSION: After adopting TPS for reporting urine cytology, there was an increase in HGUC from negative urine cytology which was subsequently confirmed on histology as cases of HGUC. The quality control of negative urines could be important monitoring the process when implementing TPS.

MDM2 amplification in malignant Brenner tumors may play a role in progression to malignancy and aid in separation from urothelial and other ovarian carcinomas.

Malignant Brenner tumor (MBT) is diagnosed in the setting of invasive high-grade carcinoma with urothelial-like morphology and the presence of an adjacent benign Brenner tumor (BBT) or borderline Brenner tumor (BLBT). MDM2 amplification was recently detected by next-generation sequencing on a small number of MBTs, potentially significant for future targeted therapy. Experience is limited, however, and evaluation of widely available MDM2 immunohistochemistry (IHC) has not been performed to determine clinical utility. After confirming all diagnoses morphologically and immunohistochemically, we performed MDM2 IHC on 4 MBTs, 3 BLBTs, 26 BBTs, 142 high-grade serous carcinomas (HGSC), 6 ovarian endometrioid carcinomas (OEC) with urothelial-like morphology, and 49 high-grade urothelial carcinomas (HGUC). MDM2 IHC was considered positive with diffuse (>25%) nuclear reactivity; in cases of patchy staining (10-25% nuclear reactivity), MDM2 was considered equivocal. Positive staining in <10% of cells was considered negative. In cases with positive or equivocal staining, MDM2 amplification was evaluated by fluorescence in-situ hybridization (FISH). Three MBTs (75%) showed diffuse nuclear reactivity for MDM2 by IHC, a finding corroborated by amplification of MDM2 in all three cases. One MBT and 2 BLBTs showed equivocal MDM2 IHC, but all three were negative for MDM2 amplification. The final BLBT, as well as all BBTs, HGSC, OEC, and HGUC, were negative for MDM2. In conclusion, our limited cohort confirms MDM2 amplification in MBT and suggests that MDM2 IHC may have an influence in rare diagnostically challenging cases.

Bone and soft tissue sarcomas in cerebrospinal fluid and effusion: A 20-year review at our institution.

BACKGROUND: The literature on bone and soft tissue sarcomas (BSTSs) involving effusions and cerebrospinal fluid (CSF) is very limited. METHODS: A computerized search for fluid cytology with a sarcoma diagnosis from 2000 to 2020 was performed. All available cases, including the clinical follow-up, were reviewed. RESULTS: A total of 57 fluids specimens from 36 BSTSs were identified (9 rhabdomyosarcomas, 6 angiosarcomas, 5 epithelioid hemangioendotheliomas, 3 dedifferentiated liposarcomas, 2 chondrosarcomas, 1 extraskeletal myxoid chondrosarcoma, 3 Ewing sarcomas, 2 undifferentiated sarcomas, 3 osteosarcomas, 1 synovial sarcoma, and 1 hybrid low-grade fibromyxoid sarcoma/sclerosing epithelioid fibrosarcoma). There were 22 males and 14 females. The age range was 4 to 82 years (median, 45 years). Sites of involvement included pleural fluid (n = 38), peritoneal fluid (n = 14), and CSF (n = 5). Twenty-four cytology cases were available for review. The cytologic features were nonspecific and ranged from dyshesive to clusters of round, epithelioid, pleomorphic, and occasionally spindle-shaped malignant cells that could easily mimic other non-BSTS malignant tumors. The diagnosis of BSTS was made by comparison with a prior specimen and/or ancillary studies (molecular or immunohistochemical stains). The prognosis was poor because 95% of the patients died of their disease. CONCLUSIONS: The incidence of BSTS in fluid cytology is extremely rare, and it can have cytologic features similar to those of non-BSTS malignancies. Although, in most cases, a comparison with a prior known BSTS specimen may suffice, the use of ancillary studies is extremely helpful in arriving at the correct diagnosis. However, in cases with no known prior malignancy, including BSTS in the differential diagnosis is prudent for preventing misdiagnosis.

Smooth muscle tumors of the gastrointestinal tract: an analysis of prognostic features in 407 cases.

Smooth muscle tumors represent the second most common mural mesenchymal neoplasm in the gastrointestinal tract, but established criteria for prognostic assessment of these tumors are lacking. A large cohort of surgically resected intramural gastrointestinal smooth muscle tumors from 31 institutions was analyzed to identify potential prognostic features. Pathologic features were assessed by expert gastrointestinal and/or soft tissue pathologists at each center. Immunohistochemical confirmation was required. A total of 407 cases from the esophagus (n = 97, 24%), stomach (n = 180, 44%), small bowel (n = 74, 18%), and colorectum (n = 56, 14%) were identified. Patients ranged in age from 19 to 92 years (mean 55 years), with a slight female predominance (57%). Mean tumor size was 5.4 cm, with the largest tumor measuring 29 cm. Disease progression following surgery, defined as local recurrence, metastasis, or disease-related death, occurred in 56 patients (14%). Colorectal tumors were most likely to progress, followed by small bowel and gastric tumors. None of the esophageal tumors in this series progressed. Receiver operator characteristic analysis identified optimal cutoffs of 9.8 cm and 3 mitoses/5 mm2 for discriminating between progressive and non-progressive tumors. Histologic features strongly associated with progression by univariate analysis included moderate-to-severe atypia, high cellularity, abnormal differentiation (defined as differentiation not closely resembling that of normal smooth muscle), tumor necrosis, mucosal ulceration, lamina propria involvement, and serosal involvement (P < 0.0001 for all features). Age, sex, and margin status were not significantly associated with progression (P = 0.23, 0.82, and 0.07, respectively). A risk assessment table was created based on tumor site, size, and mitotic count, and Kaplan-Meier plots of progression-free survival for each subgroup revealed progression-based tiers. Based on our findings, it appears that nonesophageal gastrointestinal smooth muscle tumors measuring >10 cm and/or showing ≥3 mitoses/5 mm2 may behave aggressively, and therefore close clinical follow-up is recommended in these cases.

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.

Effect of two herbal mouthwashes on gingival health of school children.

This study aimed at determining the effect of indigenously prepared neem and mango chewing stick mouthwashes on plaque and gingival indices. A sample of 105 children aged 12-15 years was randomized into three groups, namely neem, mango, and chlorhexidine mouthwash groups. All the children were examined at baseline and gingival and plaque indices were recorded. Baseline scores for plaque and gingivitis were fair and moderate, respectively, in all the three groups and there existed no statistically significant difference among them. Ten millilitres each of herbal and chlorhexidine mouthwashes (0.2%) were administered according to the group allocation twice daily for 21 days. Indices were reassessed at 21 days (immediately after intervention) and at 1 month, 2 months, and 3 months after discontinuing the mouthwashes. Statistically significant reduction (P < 0.001) in plaque index was found in all the three mouthwash groups at 21 days and at 1 month from discontinuing the mouthwash. Chlorhexidine additionally showed statistically significant reduction in plaque index at 2 months from discontinuing the mouthwash. Statistically significant reduction (P < 0.001) in gingival index was found in all the three mouthwash groups at 21 days (immediately after discontinuing the mouthwash) and at 1 and 2 months from discontinuing the mouthwash. To conclude, all the three mouthwashes were effective antiplaque and antigingivitis agents. Chlorhexidine and neem possess equivalent efficacy in reducing plaque, while chlorhexidine has superior antigingivitis properties.

Fulminant neonatal sepsis due to Streptococcus alactolyticus - A case report and review.

Group D streptococci have rarely been associated with neonatal infections. We report a case of fulminant respiratory distress syndrome (RDS) caused by Streptococcus alactolyticus in a term neonate. Gram staining revealed gram-positive cocci and culture grew group D streptococci in samples taken from trachea, ear, and nasopharynx. Streptococcus alactolyticus was identified using automated microbial identification system (Vitek 2). Histopathology showed massive pulmonary inflammation with intra-alveolar granulocytosis and secondary pulmonary bleeding as etiology of fatal outcome. To our knowledge, this is first case presenting neonatal infection caused by Streptococcus alactolyticus.

Relationship between serum lithium, salivary lithium, and urinary lithium in patients on lithium therapy.

Lithium carbonate is used in the treatment of both psychiatric and nonpsychiatric disorders. The aim of this study was to explore the relationship between serum lithium, salivary lithium, and urinary lithium. Blood, saliva, and urine samples were collected from 50 patients, and estimation of serum, salivary, and urine lithium was done using an atomic absorption spectrophotometer. Mean serum lithium was 0.75 ± 0.25 mEq/L, mean salivary lithium was 1.91 ± 0.80 mEq/L, and mean urine lithium was 7.16 ± 4.84 mEq/L. A significant direct correlation was found between serum lithium and salivary lithium (r = 0.695, p < 0.001). This correlation was higher in females (r = 0.770, p < 0.001) when compared to males (r = 0.665, p < 0.001). Even though a significant correlation was found between serum and salivary lithium levels, more studies are needed in this domain to establish salivary therapeutic monitoring as a feasible option for patients on lithium carbonate therapy.