Androgen Receptor Immunohistochemical Expression in Undifferentiated/Dedifferentiated Endometrial Carcinoma.

Uterine undifferentiated (UC)/dedifferentiated (DEAC) carcinomas are rare malignant neoplasms. They tend to pursue an aggressive clinical course with an advanced stage at presentation. It has been found that androgen receptor (AR) might play a role as a prognostic and therapeutic marker in endometrial carcinoma. However, its expression in UC/DEAC has not been investigated. Herein, the aim of this study was to evaluate the expression of AR along with estrogen receptor (ER), progestin receptor (PR), and HER2 in UC/DEAC and also in other subtypes of high-grade endometrial carcinomas. Review of our pathology database over the period of 2011 to 2019 identified 16 UC/DEAC cases (N=16). We also randomly selected other high-grade endometrial carcinomas including FIGO 3 endometrioid carcinoma (N=9), serous carcinoma (N=8), clear cell carcinoma (N=12) and carcinosarcoma (N=10) for comparison. Immunohistochemical stains for AR, ER, PR, and HER2 were performed on all 55 cases. The protein expression was evaluated both quantitatively and qualitatively. In DEAC cases both the undifferentiated component and the well-differentiated component were recorded separately. Overall, variable degrees of AR reactivity (by Allred scoring method) was present in 63% of UC/DEACs(10/16), 67% of FIGO 3 endometrioid carcinomas (6/9), 88% of serous carcinomas (7/8), 80% of carcinosarcomas (8/10), and 9% of clear cell carcinoma (1/12). AR expression was most often seen with PR (70%) or ER (60%) staining in UC/DEACs. Thirteen cases of UC/DEACs were positive for at least 1 hormone receptor. HER2 was negative in all UC/DEACs. Almost all other high-grade carcinoma cases were negative for HER2 except 20% of carcinosarcoma (2/10) and 13% of serous carcinoma (1/8) which showed 3+ HER2. Loss of AR appears to be associated with worse clinicopathologic parameters in UC/DEAC. AR is highly expressed in UC/DEAC, and in the majority of FIGO 3 endometrioid carcinomas, serous carcinomas, and carcinosarcoma. These findings suggest a potential role for androgen inhibitors in the management of patients with these tumors.

COVID-19 in recent heart transplant recipients: Clinicopathologic features and early outcomes.

BACKGROUND: The impact of COVID-19 on heart transplant (HTx) recipients remains unclear, particularly in the early post-transplant period. METHODS: We share novel insights from our experience in five HTx patients with COVID-19 (three within 2 months post-transplant) from our institution at the epicenter of the pandemic. RESULTS: All five exhibited moderate (requiring hospitalization, n = 3) or severe (requiring ICU and/or mechanical ventilation, n = 2) illness. Both cases with severe illness were transplanted approximately 6 weeks before presentation and acquired COVID-19 through community spread. All five patients were on immunosuppressive therapy with mycophenolate mofetil (MMF) and tacrolimus, and three that were transplanted within the prior 2 months were additionally on prednisone. The two cases with severe illness had profound lymphopenia with markedly elevated C-reactive protein, procalcitonin, and ferritin. All had bilateral ground-glass opacities on chest imaging. MMF was discontinued in all five, and both severe cases received convalescent plasma. All three recent transplants underwent routine endomyocardial biopsies, revealing mild (n = 1) or no acute cellular rejection (n = 2), and no visible viral particles on electron microscopy. Within 30 days of admission, the two cases with severe illness remain hospitalized but have clinically improved, while the other three have been discharged. CONCLUSIONS: COVID-19 appears to negatively impact outcomes early after heart transplantation.

Th17 and non-Th17 interleukin-17-expressing cells in chronic lymphocytic leukemia: delineation, distribution, and clinical relevance.

BACKGROUND: The levels and clinical relevance of Th17 cells and other interleukin-17-producing cells have not been analyzed in chronic lymphocytic leukemia. The objective of this study was to quantify blood and tissue levels of Th17 and other interleukin-17-producing cells in patients with this disease and correlate blood levels with clinical outcome. DESIGN AND METHODS: Intracellular interleukin-17A was assessed in blood and splenic mononuclear cells from patients with chronic lymphocytic leukemia and healthy subjects using flow cytometry. Interleukin-17A-producing cells were analyzed in formalin-fixed, paraffin-embedded spleen and lymph node sections using immunohistochemistry and immunofluorescence. RESULTS: The absolute numbers of Th17 cells in peripheral blood mononuclear cells and the percentages of Th17 cells in spleen cell suspensions were higher in patients with chronic lymphocytic leukemia than in healthy subjects; in six out of eight paired chronic lymphocytic leukemia blood and spleen sample comparisons, Th17 cells were enriched in spleen suspensions. Circulating Th17 levels correlated with better prognostic markers and longer overall survival of the patients. Two "non-Th17" interleukin-17-expressing cells were identified in chronic lymphocytic leukemia spleens: proliferating cells of the granulocytic lineage and mature mast cells. Granulocytes and mast cells in normal spleens did not express interleukin-17. Conversely, both chronic lymphocytic leukemia and healthy lymph nodes contained similar numbers of interleukin-17+ mast cells as well as Th17 cells. CONCLUSIONS: Th17 cells are elevated in chronic lymphocytic leukemia patients with better prognostic markers and correlate with longer survival. Furthermore, non-Th17 interleukin-17A-expressing cells exist in chronic lymphocytic leukemia spleens as maturing granulocytes and mature mast cells, suggesting that the microenvironmental milieu in leukemic spleens promotes the recruitment and/or expansion of Th17 and other IL-17-expressing cells. The pathophysiology of Th17 and non-Th17-interleukin-producing cells in chronic lymphocytic leukemia and their distributions and roles in this disease merit further study.

Utility of cytokeratin 5/6 and high-molecular-weight keratin in evaluation of cauterized surgical margins in excised specimens of breast ductal carcinoma in situ.

Evaluation of the surgical margins of excision specimens for ductal carcinoma in situ (DCIS) of breast is challenging due to cautery artifact introduced in the specimen at the time of surgery. Cautery destroys the cytoarchitectural features at the tissue margins and makes the distinction between usual ductal hyperplasia (UDH) and DCIS difficult. Previous studies have shown the value of immunohistochemical staining for cytokeratin 5/6 (CK5/6) and high-molecular-weight keratin (HMWK) in distinguishing UDH from DCIS. We hypothesized that staining for CK5/6 and HMWK (34bE12) may be helpful in evaluating the cauterized surgical margins, given the 2 antibodies follow the same pattern as described in the preserved foci of the 2 entities. Forty-three excised breast specimens were stained for CK5/6 and HMWK (34bE12). Study material was divided into 5 groups: DCIS without cautery artifact, UDH without cautery artifact, UDH with cautery artifact, DCIS with mild-to-moderate cautery artifact morphologically recognizable as involving the surgical margin on hematoxylin and eosin stain, and DCIS with severe cautery artifacts precluding the evaluation of surgical margins on hematoxylin and eosin stain. A comparative evaluation of pattern, extent, and intensity of the 2 immunostains was done. Our results strongly suggest that antibodies for CK5/6 and HMWK (34bE12) may be useful in determining the presence of DCIS at surgical margins even in the event of severe cautery artifact.

Mucinous Cystadenocarcinoma of the Breast: Report of 2 Cases Including One With Long-Term Local Recurrence.

Primary mucinous cystadenocarcinoma (MCA) of breast is an exceedingly rare tumor with histologic resemblance to MCA arising in ovary, pancreas, and gastrointestinal tract. In this article, we present 2 additional cases of MCA of breast, one highlighting the diagnostic challenges of a rare entity that may potentially lead to unnecessary chemotherapy and the second case presenting with recurrence after 8 years of primary surgical excision defying the indolent behavior reported in the literature. To our knowledge, this is the first reported instance of such behavior.

Young investigator challenge: Cadherin-17 and SATB2 in cytology specimens: Do these new immunostains help in differentiating metastatic colorectal adenocarcinoma from adenocarcinomas of other origins?

BACKGROUND: Cadherin-17 (intestinal peptide-associated transporter) and SATB2 (SATB homeobox 2) immunoexpression has recently been described in surgical pathology to have value in establishing the colorectal origin of metastatic adenocarcinoma. However, to the authors' knowledge, the role of these markers in metastatic colorectal adenocarcinoma (MCA) in cytology has not been addressed to date. In the current study, the authors evaluated the contribution of cadherin-17 and SATB2 to the diagnosis of MCA in cytology specimens and compared these two novel markers with the standard gastrointestinal immunohistochemistry panel in an attempt to identify the optimal panel. METHODS: A total of 43 MCA cytology cases and 68 metastatic noncolorectal adenocarcinoma (non-MCA) cytology controls were stained for SATB2; cadherin-17; and the standard panel of cytokeratin (CK) 7, CK20, and Caudal-Type Homeobox Transcription Factor 2 (CDX2). Staining intensity and percentage of positive cells were recorded. Sensitivity and specificity values for immunostains individually and in combination were computed and compared. RESULTS: Despite specificities of 83.8% and 91.2%, respectively, for cadherin-17 and SATB2, when critically examining the new immunostains together with the standard panel, there was no significant difference noted with regard to prediction of MCA (vs non-MCA) compared with the standard panel alone (P < .6). CONCLUSIONS: The results of the current study reinforce that the standard gastrointestinal immunohistochemistry panel remains the gold standard for distinguishing MCA from non-MCA in cytology.

Bronchial-associated lymphoid tissue lymphoma: a clinical study of a rare disease.

Bronchial-associated lymphoid tissue (BALT) lymphoma is a distinct subgroup of low-grade B-cell extranodal non-Hodgkin's lymphoma, classified as marginal-zone lymphoma. This study was performed in order to assess the natural history of this rare entity. We evaluated retrospectively the clinical data of 22 patients with biopsy-proven BALT lymphoma at two tertiary-care institutions from 1996 to 2002. Immunophenotyping was done to confirm the abnormal populations of B-lymphoid cells in all cases, and clonality was determined by flow cytometry or molecular studies. There were 11 men and 11 women in the sample, median age 61 years (range 21-80 years); nine were asymptomatic at diagnosis. All 13 symptomatic patients had non-specific pulmonary complaints. On computed tomographic examination of the chest, 11 patients had bilateral disease, 12 had lung nodules, and 10 had a mass or air-space consolidation. In all but one case the disease was localised to the lung at diagnosis and none had peripheral blood or bone marrow involvement. Out of 22 patients, 20 received treatment in various combinations, 12 had chemotherapy and/or rituximab, six had surgery, and two received radiation therapy as primary treatment. A complete response (CR) was achieved in nine patients and a partial response was obtained in 10 patients. Seven of 10 patients who had unilateral disease achieved a CR. The estimated progression-free survival was 53 months. All patients were alive during the median follow-up period of 36 months (range 12-76 months). It appears that BALT lymphoma tends to be localised to lung at the time of diagnosis, responds well to local or systemic therapy, and has a favourable prognosis.

Comparative study in the expression of p53, EGFR, TGF-alpha, and cyclin D1 in verrucous carcinoma, verrucous hyperplasia, and squamous cell carcinoma of head and neck region.

Verrucous carcinoma (VC) is a locally invasive, nonmetastasizing variant of squamous cell carcinoma (SCC) with distinct clinical and histologic features. Molecular alterations detectable by immunohistochemical analyses in VC have not been extensively studied. This study investigates the expression of p53, epidermal growth factor receptor (EGFR), transforming growth factor-alpha (TGF-alpha), and cyclin D1 in VC, verrucous hyperplasia (VH), and classic SCC of the head and neck. Twenty-six cases of VC, 12 cases of SCC of various differentiations, and 4 cases of VH were studied. Formalin-fixed, paraffin-embedded archival material was used for immunohistochemistry (avidin-biotin immunoperoxidase technique) to study the expression of oncogenes and their tumor markers. Identification of p53 protein was found in 100% of VH, 88% of VC, and 100% of SCC. EGFR expression was noted in 25% of VH, 54% of VC, 40% of well-differentiated SCC (WDSCC), and 100% of moderately and poorly differentiated SCC (MDSCC/PDSCC). TGF-alpha was detected in 25% of VH, 88% of VC, 80% WDSCC, and 100% of MDSCC/PDSCC. Cyclin-D1 expression was seen in 75% of VH, 35% of VC, 100% of WDSCC, 67% of MDSCC, and 50% of PDSCC. Correlation between the level of expression of all markers and the grade of this group of squamous lesions revealed statistically significant correlation coefficients for p53 and EGFR but not for TGF-alpha and cyclin D1.

Role of PAX-8, CD5, and CD117 in distinguishing thymic carcinoma from poorly differentiated lung carcinoma.

AIM: To determine if PAX-8, CD5, and CD117 can differentiate thymic carcinoma from poorly differentiated lung carcinoma. DESIGN: Archived cases of thymic (n=13) and poorly differentiated lung (n=15) carcinoma were analyzed for intensity and proportion of expression of PAX-8, CD117, and CD5. RESULTS: PAX-8 was positive in 69.2% of thymic and 5.8% of lung carcinomas. CD117 was positive in 84% of thymic and 26.6% of lung carcinomas. A total of 53% of thymic and none of the lung carcinomas were positive for CD5. Forty-six percent, 53%, and 69% of thymic carcinomas were dual positive for combinations of CD5/PAX-8, CD117/CD5, and CD117/PAX-8, respectively. None of the lung carcinomas were dual positive. Positivity for any 2 of the 3 markers was seen in 84% of thymic and none of the lung carcinomas. Triple positivity was seen in 53% of thymic carcinomas. CONCLUSION: Adding PAX-8 to CD117 and CD5 increases the diagnostic yield for thymic carcinoma.

Usefulness of GATA3 and p40 immunostains in the diagnosis of metastatic urothelial carcinoma in cytology specimens.

BACKGROUND: GATA3 (GATA-binding protein 3) expression in urothelial carcinoma (UC) and mammary carcinomas has been recently reported. However, to the authors' knowledge, studies examining GATA3 staining of metastatic UC (MUC) in cytology specimens are lacking. Delta Np63 (p40) has been shown to be expressed highly selectively in squamous cell carcinomas (SCCs) but the literature concerning the expression of p40 in UC is limited and controversial. In the current study, the authors evaluated the usefulness of GATA3 and p40 in the diagnosis of MUC in cytology specimens. METHODS: Thirty-two MUC cytology cases and 44 controls (22 UC cases and 22 SCC cases) were stained for GATA3, p40, and p63 and nuclear staining intensity and the percentage of positive cells were recorded and compared. RESULTS: MUC cytology cases stained positive for GATA3, p40, and p63 in 78.13%, 80.65%, and 61.29% of cases, respectively, with moderate/strong staining intensity. MUC cases had a significantly higher percentage of GATA3 positivity compared with SCC controls (P<.001), but GATA3 positivity was not found to be significantly different from UC controls (90.91%) (P = .28). For p40 positivity, there was no significant difference observed between MUC cases, UC controls (95.45%), and SCC controls (90.91%) (P=.29). p63 positivity was found to be significantly lower in MUC cases compared with UC controls (95.45%) and SCC controls (95.45%) (P<.01). CONCLUSIONS: The results of the current study demonstrate that GATA3 is useful in confirming the diagnosis of MUC in cytology specimens and in distinguishing between MUC and SCC. p40 is a valuable adjunct to GATA3 in the diagnosis of MUC in cytology specimens, especially when SCC is not part of the clinical differential diagnosis.

Ossifying fibromyxoid tumor of the breast mimicking fibroadenoma: a case report and differential diagnoses.

An 80-year-old woman presented with a palpable mass in the right breast. Mammographic findings were consistent with calcified fibroadenoma. An ultrasound was performed that showed a solid nodule with peripheral calcification. A core biopsy was obtained that revealed a spindle cell proliferation with a shell of mature bone. The histologic features, in combination with immunohistochemical studies, were those of an ossifying fibromyxoid tumor. Complete excision of the specimen further confirmed the diagnosis. To the best of our knowledge, this is the first reported case of ossifying fibromyxoid tumor occurring in the breast. We review the current literature on ossifying fibromyxoid tumor and discuss the differential diagnoses when confronted with bland spindle cells on a core biopsy of the breast.

Consolidation of the North Shore-LIJ Health System anatomic pathology services: the challenge of subspecialization, operations, quality management, staffing, and education.

OBJECTIVES: To describe our experience, both in meeting challenges and in reporting outcomes, of the consolidation of anatomic pathology services in the North Shore-LIJ Health System in February 2011. METHODS: We addressed issues of governance, personnel, physical plant, quality programming, connectivity, and education. CONCLUSIONS: The highly regulated nature of the laboratory industry and the fact that patient care necessarily never pauses require that such a consolidation take place without a break in service or degradation in turnaround time and quality while engaging personnel at all levels in the extra duties related to consolidation. Subspecialization has allowed us to better meet the needs of our in-system health care community while increasing our access to the competitive outreach marketplace.

Differentiating high-grade cervical intraepithelial lesion from atrophy in postmenopausal women using Ki-67, cyclin E, and p16 immunohistochemical analysis.

OBJECTIVE: In postmenopausal women, differentiating high-grade cervical intraepithelial neoplasia (CIN 2,3) from atrophic uterine cervical squamous epithelium histologically may pose a diagnostic challenge. Recent studies have indicated the value of using a combination of Ki-67, cyclin E, and p16 immunohistochemical analysis in recognizing CIN 2,3. In this study, we compared the staining features of Ki-67, cyclin E, and p16 in cervix specimens from postmenopausal women to distinguish CIN 2,3 from atrophy. METHODS: Twenty-six formalin-fixed paraffin-embedded archival cervical specimens (4 biopsy, 8 laser cone, and 14 total hysterectomy samples) were selected from 25 women 50 to 80 years of age (mean = 64 years). Cases included CIN 2,3 (n = 10), atrophy (n = 9), and coexistent CIN 2,3 and atrophy (n = 6). Slides were stained with monoclonal antibodies to Ki-67, cyclin E, and p16 using the avidin-biotin-peroxidase method. Strength of staining was graded as 1+ to 3+. Pattern of staining was described as diffuse, patchy, or scattered. Ki-67 staining restricted to the basal/parabasal zone was scored as negative. RESULTS: All CIN 2,3 cases demonstrated variable positivity for Ki-67, cyclin E, and p16. Most CIN 2,3 cases showed strong p16 (81.3%) and Ki-67 (75.0%) reactivity, while only 31.3% of them showed strong cyclin E activity. Some CIN 2,3 cases demonstrated strong p16 but weak Ki-61 and cyclin E reactivity. All atrophic epithelia were negative for p16, cyclin E, and Ki-67. In coexistent CIN 2,3 and atrophy cases, the three-antibody panel clearly demarcated the transition from benign to neoplastic epithelia. CONCLUSION: P16 is the most valuable marker followed by Ki-67 for differentiating CIN 2,3. While cyclin E appears to add limited value on these two markers. Therefore, although the three-antibody immunohistochemical panel (p16, Ki-67, and cyclin E) can be a valuable adjunct to routine hematoxylin-eosin staining, it is also possible to use the two-antibody panel (p16 and Ki-67) to effectively distinguish CIN 2,3 from atrophy in postmenopausal women.