The estrogen receptor (ER)-beta isoform has been recently identified to be distinct from ERalpha isoform and regulates separate sets of genes, and can exert opposite signaling functions depending on the ligand and response elements. Previous studies of ERbeta have been at the mRNA level and few by immunohistochemistry, and the results are inconsistent. In this study the authors compared expression of ERbeta with those of other prognostic biomarkers by immunohistochemistry on tissue microarray slides, and with morphologic parameters on 147 cases of primary breast cancer. Immunoreactivity of more than 10% of cancer cells was considered to be positive. Associations between categoric variables were analyzed using the chi test, and a P value less than 0.05 was considered to be significant. ERbeta was expressed in benign epithelium and stromal cells, and breast cancer cells in 59% of different histologic types of breast cancer. ERbeta was coexpressed with ERalpha in 45% of cases. There was a statistically significant association between expression of ERbeta and Her-2/neu (P<0.000), cathepsin D (P<0.02), p53 (P<0.03), and PS2 (P<0.002). Ki-67 was almost exclusively expressed in ERbeta-positive cells. No statistically significant association was seen between ERbeta expression and histologic grade, DNA ploidy, or S-phase.

Oncotype DX is a 21-gene assay that quantifies the recurrence risk in estrogen receptor-positive breast cancer, which is expressed as the recurrence score (RS). Studies have shown that patients with a high-risk RS will most likely benefit from adjuvant chemotherapy, but there is no proven advantage for patients with a low-risk RS who still face an average recurrence risk of 7%. In this study, the relationship between the RS and the cell cycle-related antigen Ki-67 was assessed in 32 breast carcinomas and evaluated for a potential association. Comparison of the RS with tumor type, grade, and the Ki-67 proliferation index (PI) revealed an overall concordance. However, some tumors with a low RS revealed a surprisingly high Ki-67 PI. These cases may correspond to the 7% of low-risk RS carcinomas that recur. Therefore, the authors propose a combined evaluation of the RS and Ki-67 PI to identify tumors with high recurrence potential from the low-risk and intermediate-risk RS groups.

The distinction between lobular neoplasia and infiltrating lobular carcinoma from ductal neoplasia and infiltrating duct carcinoma with equivocal histologic features may present a challenge as this distinction has important therapeutic implications. Although E-cadherin staining has been of value in helping to make this determination, the variability of the E-cadherin staining pattern and the immunohistochemistry techniques can be problematic in clinical practice. A total of 161 cases of breast lesions previously diagnosed as lobular neoplasia and infiltrating lobular carcinoma were selected from the departmental files. Three surgical pathologists interpreted them in a blinded manner for the histology diagnoses and E-cadherin staining. E-cadherin staining was conducted on the paraffin-embedded sections of the breast lesions using two different source antibodies. Our results using morphology and E-cadherin stain agreed with the previous diagnoses of lobular neoplasia and infiltrating lobular carcinoma in 140 of 161 cases (86.9%). Among the 140 cases, three pathologists agreed with the morphologic diagnoses of lobular neoplasia and infiltrating lobular carcinoma in 100 (71.4%), two pathologists in 26 (18.6%) and one pathologist in 14 (10%). All three pathologists disagreed with the previous diagnoses of lobular neoplasia and infiltrating lobular carcinoma but reevaluated as ductal lesions in 21 cases (13.0%). E-cadherin staining was confirmatory in 136 of total 161 cases (84.5%) of both lobular and duct lesions by showing the loss of staining in lobular lesions and the presence of complete membrane staining in duct lesions. Aberrant E-cadherin reactions were retained weak or partial incomplete thin membrane reaction in lobular-type lesions and reduced membrane reaction in ductal-type lesions were seen in 25 of the total 161 cases (15.5%). E-cadherin immunoreaction with two different antibodies showed discrepant results in 5 of 78 cases tested (6.4%). This study illustrates (1) interobserver variability of the morphologic diagnoses of lobular neoplasia/infiltrating lobular carcinoma and duct neoplasia/infiltrating duct carcinoma, (2) the occasional presence of aberrant E-cadherin stain pattern in these breast lesions and (3) variability of E-cadherin immunostaining results by two different antibodies.

Patient: Male, 61Final Diagnosis: Strongyloides stercolaris-associated diarrheaSymptoms: Diarrhea • epigastric pain • nausea • weight lossMedication: IvermectinClinical Procedure: Colonic biopsiesSpecialty: Infectious DiseasesObjective:Rare diseaseBackground:Strongyloides stercoralis infection is endemic in subtropical and tropical regions but is reported rather sporadically in temperate countries. In the USA, the highest rates of infection are from the southeastern states, predominantly among immigrants. There is paucity of case reports on S. stercoralis infection among HIV-infected patients who were born and raised in the USA.Case Report:A 61-year-old male with known HIV infection (CD4 count: 235 cells/uL, undetectable HIV RNA, on antiretroviral therapy) presented with a 3-month history of diarrhea. He was initially diagnosed to have diarrhea secondary to norovirus and later with Escherichia coli. He was treated with levofloxacin but the diarrhea persisted. Stool PCR, Clostridium difficile enzyme-linked immunoassay, cryptosporidium and giardia antigen, cyclospora and isospora smear, and fecal microscopy were all negative. Peripheral blood eosinophil count was 1,000 eosinophils/mcL. Colonic biopsies revealed fragments of S. stercoralis larvae within the crypts. The patient was treated with ivermectin with improvement of symptoms. Social history revealed that he was born and raised in the northeastern USA. He was a daily methamphetamine user and engaged in anal sex with men. He denied travel to endemic areas, except for a visit to Japan more than 30 years ago.Conclusions:Our case highlights that S. stercoralis may be an underdiagnosed/under-reported cause of chronic diarrhea among HIV-infected patients. What makes this case peculiar is that the patient was born and raised in the continental USA, absence of recent travel to endemic areas, and relatively high CD4 counts. Parasitic infections, such as S. stercoralis, should be considered among HIV-infected patients with persistent diarrhea and eosinophilia regardless of ethnicity or recent travel history.

Primary ovarian malignant melanomas are extremely rare. The wide range of morphologic appearances assumed by melanomas in the ovary can cause considerable difficulty in diagnosis. The clinicopathologic features of 4 definite and 1 probable primary ovarian melanomas are presented. The patients ranged in age from 41 to 71 years. Four tumors were within teratomas with 2 showing a lentiginous pattern of melanoma in the squamous epithelium. Unusual histologic features were noted. Immunostains for S-100, HMB-45, and Melan-A were positive in all tumors. Premelanosomes were identified in 2 tumors ultrastructurally. Metastatic sites included regional nodes, peritoneal surfaces, omentum, lung, liver, brain, and bone. All 5 patients died within 18 months. Immunohistochemistry and electron microscopy aid considerably in the diagnosis of ovarian melanomas where pigmentation or teratomatous elements are absent. Familiarity with the wide range of morphologic patterns presented here will raise awareness and facilitate detection of future cases of ovarian melanoma.