Human epidermal growth factor receptor-2 (HER2) expression in FIGO3 high-grade endometrial endometrioid carcinoma: Clinicopathologic characteristics and future directions.

OBJECTIVES: To study the expression of HER2 in high-grade FIGO3 endometrial endometroid carcinoma (EEC) and to correlate our findings with the clinicopathologic characteristics of this tumor. METHODS: HER2 expression by immunohistochemistry (IHC) was performed on 10% formalin-fixed paraffin embedded tissue on cases diagnosed as FIGO3 EEC. HER2 expression was interpreted as negative (0), low (1+ and 2+) or positive (3+) using similar criteria as in the breast. HER2 amplification by Fluorescence in situ hybridization (FISH) was performed on cases interpreted as 2+ and 3+ by IHC. RESULTS: One hundred and forty-three FIGO3 EEC were identified. Of these, 70 (49%) cases were HER2 negative (IHC 0), and 73 (51%) cases expressed/amplified HER2 by IHC and/or FISH. Of the 73 cases expressing or amplifying HER2, 59 cases were IHC 1+, 12 cases were IHC 2+, and 2 cases were IHC 3+. FISH testing was performed in 12 cases. Only one of the two HER2 IHC 3+ cases showed HER2 gene amplification by FISH and the other 11 cases were not amplified. The 5-year overall survival (OS) rate for HER2 IHC 1+ cases was 92.20% (95% CI: 83.97-100.00), and the 5-year OS rate for HER2 IHC 2+/3+ cases was 89.50% (95% CI: 56.41-100.00). CONCLUSION: Our findings indicate that about one half of FIGO3 EEC variably expresses HER2 and with the emerging concept of "HER2 low", anti-HER2 agents may be explored as potential therapeutic options in these patients, for possible survival benefits.

Low-level expression of human Epidermal growth Factor Receptor-2 (HER2) in High-Grade Mullerian Tumors: Implications for therapy decision making.

Introduction: Reclassification of HER2-negative breast cancers to HER2 low-level expression allowed targeted anti-HER2 therapy in about 60% of patients, improving outcome. The high recurrence rates and often dismal outcomes with current therapies of high-grade Mullerian carcinomas, offers opportunity to explore anti-HER2 therapies in the gynecologic tract carcinomas. We investigated HER2 low expression as currently defined in breast carcinomas. Methods: We reviewed all high-grade Mullerian cancers between 2016 and 2021, where HER2 by IHC and/or FISH tests were available. Additional clinical information was recorded, and statistical analysis was performed using SPSS (version 27). Results: Forty (49.4%) tumors were endometrial, 20 (24.7%) ovarian, 16 (19.8%) fallopian tubal, and 5 (6.2%) primarily peritoneal. Overall, 17 (21.0%) were HER2 positive (IHC 3+/IHC 2+/FISH amplified), 31 (38.3%) HER2 low (IHC 1+/2+/FISH non-amplified), and 30 (37.0%) were HER2 negative (IHC = 0). HER2 low expression was noted in 15% ovarian, 25% fallopian tubal, 53% endometrial, and 60% peritoneal tumors; 34% and 21% of serous carcinomas, 63% and 13% of carcinosarcomas, and 67% and 33% of endometrioid carcinomas were HER2 low and HER2 positive respectively. HER2 negative and HER2 low expression had a significant association with primary tumor location (p = 0.001); endometrium and peritoneal tumors were more likely to be HER2 low and HER2 negative. During a mean follow-up of 13.2 months (range: 1-34), 5% of the patients were deceased. Conclusions: Based on the current HER2-low recommendations in the breast, about one-third of patients with high-grade Mullerian carcinomas might qualify for anti-HER2 therapy with a potential for improved progression-free and overall survival.

Mammary stromal-epithelial lesions with myofibroblastic stroma and HMGA2 overexpression linked smooth muscle differentiation, a case series from single institution.

Fibroadenoma and phyllodes tumor are the prototypical mammary fibroepithelial lesions (FELs). Recently, a subset of FELs, identified as stromal-epithelial lesion (SEL) with myofibroblastic stroma have been labelled as myofibroepithelial nodule (MFN). The MFN stromal cells are diffusely positive for SMA immunostaining and frequently show unusual histological features including irregular borders. There is limited literature on FELs with myofibroblastic or smooth muscle stroma. The etiology of the variation in the FEL stromal histology and its clinical significance is unknown. In this short report we describe clinicopathologic features of six FELs with myofibroblastic and/or smooth muscle stroma. We also report immunohistochemical overexpression of HMGA2 in 2 FELs that contained stromal smooth muscle differentiation suggesting a link to mammary myoid hamartoma. On limited follow up all the 6 FELs with myofibroblastic or smooth muscle stroma had benign outcome. The HMGA2 overexpressing FEL with smooth muscle stroma and myoid hamartoma of the breast show overlapping etiology, and histological features.

Medullary colonic carcinomas present with early-stage disease and do not express neuroendocrine markers by immunohistochemistry.

Background: Medullary colonic carcinoma (MCC) is a rare and distinct phenotype of colorectal cancers characterized histologically by sheets of malignant cells with vesicular nuclei, prominent nucleoli, and abundant eosinophilic cytoplasm, exhibiting prominent infiltration by lymphocytes and neutrophilic granulocytes. We present the clinicopathologic and immunohistochemical characteristics of this rare tumor in our patient population. Methods: Eleven cases diagnosed with MCC from 1996-2020 met the diagnostic histologic criteria and had tissue blocks available for further analysis. Immunohistochemistry for mismatch repair deficiency, CDX2, synaptophysin, and chromogranin, and microsatellite instability testing by polymerase chain reaction were performed. Additional clinical information was obtained from the electronic medical records. Results: The median age at diagnosis was 69 years. MCC was more common in women (64%) than men (36%) and all (100%) cases involved the right colon. The median carcinoembryonic antigen level at diagnosis was 2.8 ng/mL. Lymphovascular invasion and perineural invasion occurred in 64% and 9% of cases, respectively. Synaptophysin and chromogranin showed no expression in any of the cases (0%), and CDX2 was only expressed in 18% of cases by immunohistochemistry. Most patients (73%) presented with stage II disease and 7 (64%) cases were microsatellite instability-high. Only lymph node metastasis showed an association with overall survival (OS) (hazard ratio 0.04, 95% confidence interval 0.0003-0.78; P=0.035). During a median follow up of 1.25 years, the median OS was not estimable as the survival curve did not reach the median point of survival, indicating that more than half of the patients were still alive at the end of the study. Conclusion: Based on our experience, neuroendocrine markers, including synaptophysin and chromogranin, are not expressed in MCC, and many patients present with early-stage disease.

Variants of in situ carcinoma of the endometrium: Clear cell and gastrointestinal types, with a review of the literature.

Two precursor lesions are commonly associated with endometrial carcinoma. Atypical endometrial hyperplasia/endometrial intraepithelial neoplasia is a known precursor lesion of endometrial endometrioid carcinoma, while endometrial intraepithelial carcinoma, is a recognized precursor lesion of endometrial high-grade serous carcinoma. Other than these two recognized entities, other rare precursor lesions for endometrial carcinoma do exist, although reported cases are relatively few and not universally recognized. This therefore poses diagnostic challenges in clinical practice. Here, we describe a series of rare precursor lesions of the endometrium identified at our institution, including clear cell and gastrointestinal variants, their morphologic and immunohistochemical characteristics, and review current literature regarding these variants. The information provided may guide the proper diagnosis and ultimately lead to effective clinical management in every-day practice.

A clinicopathologic and immunohistochemical study of primary and secondary breast angiosarcoma.

BACKGROUND: We aimed to study the clinicopathologic and immunohistochemical (IHC) (CD117, c-Myc, and p53) characteristics, and overall survival of primary and secondary breast angiosarcoma (BAS). METHODS: This was a retrospective study of BAS cases diagnosed between 1997 and 2020 at our institution. Hematoxylin and eosin-stained slides were reviewed for tumor morphology, margin status, and lymph node metastasis. CD117, p53, D2-40, CD31, and c-Myc IHC stains were performed on 11 viable tissue blocks. Additional clinical information was obtained from the electronic medical records. RESULTS: Seventeen patients with BAS were identified. Of these, five (29%) were primary and 12 (71%) were secondary BAS, respectively. The median age at diagnosis for primary BAS was 36 years. The median age at diagnosis for secondary BAS was 67 years. The median time to secondary BAS development following radiotherapy was 6.5 years (range, 2 to 12 years). There was no significant difference between primary and secondary BAS in several histopathologic parameters examined, including histologic grade, necrosis, mitotic count, lymph node metastasis, and positive tumor margins. There was also no difference in CD117, p53, D2-40, CD31, and c-Myc expression by IHC between primary and secondary BAS. During a median followup of 21 months, primary BAS had two (40%) reported deaths and secondary BAS had three (25%) reported deaths. However, this difference in survival between both groups was not statistically significant (hazard ratio, 0.51; 95% confidence interval, 0.09 to 3.28; p = .450). CONCLUSIONS: BAS is a rare and aggressive disease. No histologic, IHC (CD117, c-Myc, and p53), or survival differences were identified between primary and secondary BAS in this study.

Estrogen receptor status has no prognostic relevance in metaplastic breast carcinoma.

BACKGROUND: Metaplastic breast carcinoma (MBC) is a rare histologic variant of breast cancer characterized by the presence of glandular and non-glandular components. The prognostic significance of estrogen receptor (ER) status has been scarcely studied in these tumors. We therefore investigated the prognostic relevance of ER status in MBC within our patient population. DESIGN: We reviewed MBC cases (n = 125) between January 2000 and September 2019. Histologic slides were reviewed for variables including tumor morphology and hormonal status. Additional clinical information was obtained from the electronic medical records. RESULTS: Of the 125 patients, 15 (12%) had ER positive tumors and 110 (88%) had ER negative tumors. Eleven (73%) ER positive tumors had ER positivity > 10% and 4 (27%) had ER positivity ≤ 10%. ER positive tumors had a smaller median tumor size of 2.5 cm, compared with ER negative tumors with median tumor size 3.05 cm, however this difference was not statistically significant (P = 0.82). There were no statistical differences between ER positive and ER negative tumors in terms of histologic grade (P = 0.34), histologic subtype (P = 0.65), clinical stage (P>0.99) or human epidermal growth factor receptor 2 (HER2) expression (P = 0.29). There was also no difference in overall survival (OS) between ER positive and ER negative metaplastic breast cancers (HR = 0.35, 95% CI, 0.003-2.67, P = 0.39). CONCLUSION: Our experience suggests that ER positivity has no prognostic relevance in MBC. Regardless of ER expression status, there were no statistically significant differences in overall survival between ER positive and ER negative MBC.

COVID-19 Vaccine Hesitancy among Arab Americans.

(1) Background: Coronavirus disease-2019 (COVID-19) vaccines have a significant impact on reducing morbidity and mortality from infection. However, vaccine hesitancy remains an obstacle in combating the pandemic. The Arab American (AA) population is understudied; thus, we aimed to explore COVID-19 attitudes within this community. (2) Methods: This was a cross-sectional study. An anonymous online survey was distributed to members of different AA associations and to the community through the snowball method. (3) Results: A total of 1746 participants completed the survey. A total of 92% of respondents reported having received at least one dose of a COVID-19 vaccine. A total of 73% reported willingness to receive a booster, and 72% plan to give their children the vaccine. On multivariate analysis, respondents were more likely to be vaccine-hesitant if they were hesitant about receiving any vaccine in general. They were less likely to be vaccine-hesitant if they were immigrants, over the age of 40, up to date on their general vaccination and if they believed that COVID-19 vaccines are safe and effective in preventing an infection. The belief that all vaccines are effective at preventing diseases was also associated with lower hesitancy. (4) Conclusions: This sample of AAs have higher vaccination rates and are more willing to vaccinate their children against COVID-19 when compared to the rest of the population. However, a reemergence of hesitancy might be arising towards the boosters.

Colorectal adenocarcinoma with enteroblastic differentiation: diagnostic challenges of a rare case encountered in clinical practice.

Colorectal adenocarcinoma with enteroblastic differentiation (CAED) is a rare subtype of colonic adenocarcinoma characterized by increased α-fetoprotein (AFP) production and the expression of at least one enteroblastic marker including AFP, glypican 3 (GPC3), or Spalt like transcription factor 4 (SALL4). We report a case of a 26-year-old female who presented with low back pain and constipation which persisted despite supportive measures. Imaging revealed multiple liver lesions and enlarged retroperitoneal nodes. Tumor markers including AFP were markedly elevated. On biopsy, samples from the liver revealed infiltrating glands lined by columnar-type epithelium with mostly eosinophilic granular to focally clear cytoplasm. By immunohistochemistry, the tumor showed immunoreactivity with AFP, hepatocyte antigen, GPC3, SALL4, CDX2, SATB2, and cytokeratin 20. A colonoscopy performed subsequently revealed a mass in the sigmoid colon and biopsy of this mass revealed a similar histology as that seen in the liver. A diagnosis of CAED was made, following the results of gene expression profiling by the tumor with next-generation sequencing which identified pathogenic variants in MUTYH, TP53, and KDM6A genes and therefore supported its colonic origin. Cases such as this underscores the use of ancillary diagnostic techniques in arriving at the correct diagnosis in lesions with overlapping clinicopathologic characteristics.

Clinicopathologic Characteristics and Outcome Descriptors of Metaplastic Breast Carcinoma.

CONTEXT.­: Metaplastic breast carcinoma is an aggressive form of breast cancer that accounts for 0.5% to 3% of all breast cancers. OBJECTIVE.­: To study the clinicopathologic characteristics and outcomes of this rare disease. DESIGN.­: Retrospective study of patients with a diagnosis of metaplastic breast carcinoma between 2000 and 2019. Hematoxylin-eosin-stained slides were reviewed and additional clinical data were obtained from electronic medical records. Univariable and multivariable Cox proportional hazard regression analyses were used to determine associations between overall survival and several clinicopathologic variables. RESULTS.­: Of the 125 patients with metaplastic breast carcinoma identified, only patients with high-grade disease (N = 115) were included in the data analysis. A total of 38 participants (33%) were white, 66 (57%) were African American, and 11 (10%) belonged to other ethnicities. The median age at diagnosis was 57 years. The median tumor size was 3 cm. Heterologous histology was seen in 30% of cases. Multivariable analyses showed that patients with a larger tumor size had worse overall survival (hazard ratio [HR], 1.25; 95% CI, 1.10-1.44; P < .001). Distant metastatic disease was also associated with worse overall survival on multivariable analysis (HR, 10.27; 95% CI, 2.03-55.54; P = .005). In addition to treatment with either partial or complete mastectomies, 84 patients (73%) received chemotherapy. Multivariable analyses showed that chemotherapy had no effect on overall survival (HR, 0.53; 95% CI, 0.09-6.05; P = .55). CONCLUSIONS.­: A larger tumor size and distant metastatic disease are associated with worse overall survival in patients with metaplastic breast carcinoma. Additional studies are needed to further characterize our findings.

Evaluation of COVID-19 Vaccine Attitudes among Arab American Healthcare Professionals Living in the United States.

BACKGROUND: Vaccine hesitancy is the next great barrier for public health. Arab Americans are a rapidly growing demographic in the United States with limited information on the prevalence of vaccine hesitancy. We therefore sought to study the attitudes towards the coronavirus disease 2019 (COVID-19) vaccine amongst Arab American health professionals living in the United States. METHODS: This was a cross sectional study utilizing an anonymous online survey. The survey was distributed via e-mail to National Arab American Medical Association members and Arab-American Center for Economic and Social Services healthcare employees. Respondents were considered vaccine hesitant if they selected responses other than a willingness to receive the COVID-19 vaccine. RESULTS: A total of 4000 surveys were sent via e-mail from 28 December 2020 to 31 January 2021, and 513 responses were received. The highest group of respondents were between the ages of 18-29 years and physicians constituted 48% of the respondents. On multivariable analysis, we found that respondents who had declined an influenza vaccine in the preceding 5 years (p < 0.001) and allied health professionals (medical assistants, hospital administrators, case managers, researchers, scribes, pharmacists, dieticians and social workers) were more likely to be vaccine hesitant (p = 0.025). In addition, respondents earning over $150,000 US dollars annually were less likely to be vaccine hesitant and this finding was significant on multivariable analysis (p = 0.011). CONCLUSIONS: Vaccine hesitancy among health care providers could have substantial impact on vaccine attitudes of the general population, and such data may help inform vaccine advocacy efforts.

Human Papillomavirus Infection and Cervical Dysplasia in a Subset of Arab American Women.

Background: With limited health data on Arab Americans (AAs), we sought to describe the health-seeking behaviors, prevalence of abnormal cervical cytology and high-risk human papillomavirus (HPV) serotypes, and the relationship with socioeconomic factors among a subset of AA women. Methods: Retrospective observational cohort study of women undergoing routine cancer screening at the Arab-American Center for Economic and Social Services clinic. Data collected included demographics, tobacco use, gross monthly income, prior Papanicolaou (Pap) smear history, and results of cervical cytology and high-risk HPV testing. Results: Of 430 women, 74 (17%) reported that they had never had a Pap smear. Three hundred eighty-eight (90%) women had cervical cytology interpreted as "negative for intraepithelial lesion," the remaining 42 (10%) women had abnormal results. Thirteen (3%) women reported prior abnormal Pap smear, which was significantly associated with additional abnormal Pap smear on multivariable analyses (odds ratio 65.46; 95% confidence interval [CI] 17.01-338.62; p < 0.001). One hundred twenty-five (29%) women were tested for high-risk HPV serotypes; 106 (91%) had negative results, 4 (3%) were positive for HPV-16, 7 (6%) were positive for other high-risk serotypes, and 8 results were not recorded. A negative HPV screen was significantly associated with a negative Pap smear (Fisher's exact test p = 0.006). There was no significant association between abnormal cervical cytology and evaluated socioeconomic factors. Conclusions: Additional population based-studies to determine cervical dysplasia/cancer and HPV prevalence in women of Middle Eastern descent are needed.

A Rare Case of GATA3 Positivity in Pleomorphic Lung Carcinoma in a Patient with History of Intracystic Papillary Carcinoma of the Breast: Primary Lung or Metastatic Disease?

Pleomorphic lung carcinoma is a rare and aggressive neoplasm accounting for <1% of all lung tumors. It is more common in men and consists of spindle and/or giant cells with an epithelial component. In patients with known histories of malignancies at other sites, diagnosis of a new lung lesion may prove challenging with respect to classification as either primary or metastatic disease, especially in cases with overlapping immunohistochemical staining patterns. This was a case of a 67-year-old female with a newly discovered 1.5 cm nodule in her left lower lung lobe. Her past medical history was significant for an intracystic papillary carcinoma of the right breast diagnosed 8 years prior. Histopathologic examination of the new lung lesion revealed highly pleomorphic cells composed predominantly of neoplastic giant cells and atypical mitotic figures, with geographic areas of necrosis. However, no areas reminiscent of intracystic papillary carcinoma or other forms of breast carcinoma were seen. Immunohistochemistry showed that the tumor cells were immunoreactive for GATA3, TTF1, and napsin A and nonimmunoreactive for p40. Therefore, although this index lung tumor did show positivity with GATA3 staining, it was morphologically different from her original intracystic papillary carcinoma of the breast. In addition, intracystic papillary carcinomas are known to rarely metastasize to other organs, and GATA3 staining has been rarely reported in lung carcinomas. In summary, this case typifies the overlapping immunohistochemical staining patterns that may be seen in different tumors and the role of histopathologic morphology in arriving at the correct diagnosis.

Autopsies are indispensable in the advancement of patient care: Report of an unusual presentation and fatal outcome of an autopsy-diagnosed case of advanced idiopathic interstitial pneumonia.

Idiopathic interstitial pneumonias (IIPs) are a group of fibrosing lung disorders conferring significant morbidity and mortality to patients. Most patients with IIP first present with dyspnea and/or cough. Here, we report the case of a 53-year-old male who presented with severe abdominal pain and weight loss of approximately 100 pounds of 3-month duration. Symptoms of mild dyspnea and cough were obtained during additional history taking. Physical examination and computed tomography of the chest were suggestive of pneumonia, and he was placed on multiple antibiotics but developed worsening respiration that necessitated hyperbaric oxygen and died after 10 days. Histopathological examination of autopsy lung specimen, revealed severe lung damage secondary to a mixed IIP pattern of diffuse alveolar damage, superimposed on extensive interstitial fibrosis, with features of honeycombing, consistent with advanced interstitial/end-stage lung disease. This case typifies an unusual and fatal presentation of IIP, which may be useful in clinical practice.