Cystic neutrophilic granulomatous mastitis: A clinicopathologic study of a distinct entity with supporting evidence of a role for Corynebacterium-targeted therapy.

Cystic neutrophilic granulomatous mastitis (CNGM) is a distinct histopathologic entity characterized by neutrophilic and granulomatous inflammation surrounding clear cystic spaces. Rare gram-positive bacilli are sometimes identified within these cystic spaces. Studies in the literature have identified these gram-positive bacilli to be Corynebacterium species. We describe the clinicopathologic features of 7 cases of CNGM, including a case with evidence of Corynebacterium amycolatum. Patients were young to middle aged parous women ranging in age from 28 to 53 years (median age: 41 years). Gram-positive bacilli were identified in 4 cases, all within cystic spaces. Microbial culture from a 41-year old Hispanic woman grew Corynebacterium species on multiple occasions and Corynebacterium amycolatum was identified by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) on two separate occasions. Antibiotic susceptibility testing performed both times showed resistance to multiple antibiotics and susceptibility to vancomycin. Follow-up of all patients (range 3-12 months, median 6 months) showed a widely variable clinical course and varying response to a variety of treatment modalities. Five of the seven CNGM patients were parous, reproductive-aged Hispanic women who were born outside of the United States. Our findings further support the association of CNGM with corynebacteria and gram-positive bacilli. Furthermore, this study shows that Corynebacterium amycolatum, a nonlipophilic and multidrug-resistant corynebacterium can be associated with CNGM, hence the need for targeted antibiotic therapy. We propose identifying corynebacteria to the species level and performing antibiotic susceptibility testing in patients with CNGM because of the varied susceptibility testing profile that has been reported among different species of corynebacteria.

Prevalence of HPV Infection in Racial-Ethnic Subgroups of Head and Neck Cancer Patients.

The landscape of HPV infection in racial/ethnic subgroups of head and neck cancer (HNC) patients has not been evaluated carefully. In this study, a meta-analysis examined the prevalence of HPV in HNC patients of African ancestry. Additionally, a pooled analysis of subject-level data was also performed to investigate HPV prevalence and patterns of p16 (CDNK2A) expression amongst different racial groups. Eighteen publications (N = 798 Black HNC patients) were examined in the meta-analysis, and the pooled analysis included 29 datasets comprised of 3,129 HNC patients of diverse racial/ethnic background. The meta-analysis revealed that the prevalence of HPV16 was higher among Blacks with oropharyngeal cancer than Blacks with non-oropharyngeal cancer. However, there was great heterogeneity observed among studies (Q test P<0.0001). In the pooled analysis, after adjusting for each study, year of diagnosis, age, gender and smoking status, the prevalence of HPV16/18 in oropharyngeal cancer patients was highest in Whites (61.1%), followed by 58.0% in Blacks and 25.2% in Asians (P<0.0001). There was no statistically significant difference in HPV16/18 prevalence in non-oropharyngeal cancer by race (P=0.682). With regard to the pattern of HPV16/18 status and p16 expression, White patients had the highest proportion of HPV16/18+/p16+ oropharyngeal cancer (52.3%), while Asians and Blacks had significantly lower proportions (23.0% and 22.6%, respectively) [P <0.0001]. Our findings suggest that the pattern of HPV16/18 status and p16 expression in oropharyngeal cancer appears to differ by race and this may contribute to survival disparities.

Pattern of cervical biopsy results in cases with cervical cytology interpreted as higher than low grade in the background with atrophic cellular changes.

OBJECTIVE: The cytomorphological changes associated with atrophic cellular pattern (ACP) in cervical cytology smears may mimic high-grade squamous intraepithelial lesion (HSIL). Due to this, there may be higher chances of cytomorphological overinterpretation in cases with ACP. Estrogen therapy (ET) (topical or systemic) would reverse the changes related to atrophy and repeat Pap smear after ET should correct the false positives. This approach would minimize the unindicated invasive interventions. However, performing immediate biopsies following "higher than low-grade squamous intraepithelial lesion (LSIL) (atypical squamous cells-cannot exclude HSIL, low-grade squamous intraepithelial lesions-cannot exclude HSIL, and HSIL) interpretations" in such cases, is a general trend. Pap smears with "higher than LSIL interpretations" in association with ACP over a period of 10 years were selected. MATERIALS AND METHODS: A total of 657,871 cases over 10 years were reviewed, of which 188 Pap smears interpreted as higher than LSIL interpretations with ACP were selected randomly for this study. RESULT: Of these 188 cases, 67 underwent biopsies which were reviewed and compared with 67 biopsies performed for "higher than LSIL interpretation" cases without ACP. The follow-up biopsy material was reviewed including elective p16 immunohistochemistry with other clinical details including high-risk HPV test results as indicated. CONCLUSION: The findings demonstrated that Pap smears with ACP have higher false positives due to tendency for cytomorphologic overinterpretation as compared to non-ACP group.

Synchronous Diagnosis of De Novo Acute Myeloid Leukemia with inv(16)(p13q22) and Chronic Lymphocytic Leukemia: A Case Report and Review of the Literature.

The occurrence of de novo acute myeloid leukemia (AML) with chronic lymphocytic leukemia (CLL) is rare. Most cases of hematologic malignancies such as AML occurring in patients with pre-existing CLL are therapy-related. In this report, we describe a 65-year-old male with no past history of a hematolymphoid malignancy, who presented with abdominal pain. He was evaluated for acute diverticulitis, and incidentally found to have 14% circulating blasts upon peripheral blood smear review for anemia and thrombocytopenia. Bone marrow biopsy revealed 30-40% blasts and lymphoid aggregates. In conjunction with cytogenetics studies, a diagnosis of de novo AML with inv(16)(p13q22) CBFB-MYH11, trisomy 8, monosomy 18, and concurrent CLL with trisomy 12 was made. Serial FISH studies were used to demonstrate that the nuclei with (CBFB-MYH11) fusion did not have trisomy 12 and it was concluded that AML and CLL cells arose from separate clones. He died 3 weeks following presentation from complications of diverticulitis. To our knowledge, this is the second reported case of de novo AML with inv(16) and CLL.

siRNA-Encapsulated Hybrid Nanoparticles Target Mutant K-ras and Inhibit Metastatic Tumor Burden in a Mouse Model of Lung Cancer.

There is an unmet need in the development of an effective therapy for mutant K-ras-expressing non-small-cell lung cancer (NSCLC). Although various small molecules have been evaluated, an effective therapy remains a dream. siRNAs have the potential to downregulate mutant K-ras both at the protein and mRNA levels. However, a safe and effective delivery of siRNAs to tumors remains a limitation to their translational application in the treatment of this highly debilitating disease. Here we developed a novel hybrid nanoparticle carrier for effective delivery of anti-mutant K-ras to NSCLC (AKSLHN). The ability of this treatment modality to regress lung tumors in mouse models was evaluated as a monotherapy or as a combination treatment with erlotinib. Further, the toxicity of this treatment modality to healthy tissues was evaluated, along with its ability to elicit immune/inflammatory reactions. The results suggest that this treatment modality is a promising prospect for the treatment of mutant K-ras-expressing NSCLC without any accompanying toxicity. However, further understanding of the cellular-level interaction between AHSLHN and erlotinib needs to be attained before this promising treatment modality can be brought to the bedside.