Ovarian Malignant Mixed Germ Cell Tumor With Prominent Embryoid Bodies (Polyembryoma Background): A Case Report and Literature Review.

Ovarian malignant mixed germ cell tumors are rare tumors occurring in young women. The presence of prominent embryoid bodies in these tumors is extremely uncommon. Herein, we report such a case, with a histomorphologic description and immunohistochemical and fluorescence in situ hybridization analyses.

Single organ microenvironment and the common features of tumors of leukemia, lymphoma, and myeloma cells growing there: A literature review.

OBJECTIVE: To explore whether the growth and treatment resistance of lymphoma and myeloma tumors is similar to that previously observed in leukemic and solid tumors growing in the same organ microenvironment. METHODS: All published cases of 3 primary hematologic malignancies in breast, without systemic involvement, were identified, with follow-ups solicited from authors. Treatment approaches were analyzed to highlight the most effective. RESULTS: Similar histologic features and biology among primary tumors of leukemia, lymphoma, plasmacytoma, and solid breast cancer was revealed. Review of treatments: tumor-directed, chemotherapy, or combination showed the benefit of tumor removal, and use of systemic agents in adjunct, not primary, treatment. Optimal assessment is limited by few cases of PET/CT verifying limited tumor extent. The common biology observed and cases of long survival after tumor/stroma eradication point to the complicity of organ microenvironment in the chemoresistance and treatment failure commonly observed in patients. CONCLUSIONS: The interaction of an organ microenvironment, particularly its adipocytes, with malignant cells, results in similar histologic changes, metastatic potential, and chemoresistance in 3 hematologic malignancies and solid cancers. Improved survival in hematologic malignancies could result from adopting PET/CT to find tumor and its extent, eradicating tumor, and elucidating common therapeutic targets.

Ultrasound-guided fine-needle aspiration biopsy of thyroid neoplasms with lipomatous stroma: Report of two cases.

Thyroid tumors with abundant adipose tissue component are rare, reportedly accounting for 0.98-2.8% of all thyroid nodules, and include entities such as thyroid lipoadenoma and thyroid carcinoma with lipomatous stroma (TCLS). They may be encountered on fine-needle aspiration biopsy (FNAB), which is widely used in evaluation of thyroid nodules. However, due to their relative rarity, adipose elements rarely are recognized preoperatively in these tumors. Herein, we report two cases of thyroid tumors with abundant adipose tissue, along with cytologic, histologic, and ultrasonographic features. Although an intermixture of adipose tissue and thyroid follicular cells is the key cytologic feature of thyroid tumors with adipose stroma, other cytologic findings, such as abundant fat droplets or isolated fragments of adipose tissue, also should raise the possibility of a fat-containing tumor, particularly when a biopsy is performed by a cytopathologist under ultrasonographic guidance and adequate radiologic-pathologic correlation. Cytopathologists should be aware that overlooking lesional adipose tissue within a thyroid neoplasm might give the false impression of a non-diagnostic or sparsely cellular FNAB specimen.

The significance of ASC-H and LSIL dual interpretation with risk stratification: one institution experience.

INTRODUCTION: The 2014 Bethesda System categorizes squamous lesions as low-grade squamous intraepithelial lesions (LSIL) and high-grade squamous intraepithelial lesions (HSIL). It also includes intermediate morphologic terminology, such as atypical squamous cells of undetermined significance (ASC-US) and atypical squamous cells, cannot rule out a high grade squamous intraepithelial lesion (ASC-H). Consensus is lacking if when ASC-H is present in an unequivocal LSIL (LSIL + ASC-H) versus ASC-H alone predicts a neoplasm with a different biologic behavior and which is its association with high-risk human papillomavirus (HPV). MATERIALS AND METHODS: We reviewed the Columbia University Medical Center Pathology department patient's database from October 2012 through December 2014 and found 2498 cytology samples of LSIL, ASC-H, HSIL, and LSIL + ASC-H with both follow-up histologic samples and HPV tests by Roche cobas. Our objective was to identify, if any, differences in biologic behavior and HPV status present in LSIL + ASC-H compared with ASC-H and other lesions. RESULTS: CIN2+ was documented in tissue examination in 102 from 311 LSIL + ASC-H (32.8%), 101 from 219 ASC-H (46.1%), 252 from 326 HSIL+ (77.3%), and 150 from 1642 LSIL (9.08%). HPV distribution shows significant differences between all diagnostic categories. CONCLUSIONS: LSIL + ASC-H appears to have a distinctive HPV distribution pattern that clearly differs from ASC-H and LSIL and approaches HSIL; however, the predictive value for CIN2+ appears higher for ASC-H than LSIL + ASC-H. Our literature review identified conflicting findings, probably suggesting a lack of reproducibility in cytologic criteria and the need for consistent inclusion of ASC-H and LSIL when both are present.

Third-trimester placentas of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive women: histomorphology, including viral immunohistochemistry and in-situ hybridization.

AIMS: The wide variety of affected organ systems associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection highlights the need for tissue-specific evaluation. We compared placentas from SARS-CoV-2-positive and SARS-CoV-2-negative women in our hospital in New York City, which became the epicenter of the coronavirus disease 2019 pandemic in March 2020. To date, some limited studies have been published on placentas from SARS-CoV-2-positive women. The aim of our study, in addition to describing histomorphology, was to utilize in-situ hybridization (ISH) for the S-gene encoding the spike protein and immunohistochemistry (IHC) with the monoclonal SARS-CoV-2 spike antibody 1A9 for placental evaluation. METHODS AND RESULTS: In this study, 51 singleton, third-trimester placentas from SARS-CoV-2-positive women and 25 singleton, third-trimester placentas from SARS-CoV-2-negative women were examined histomorphologically according to the Amsterdam Criteria and with ISH and/or IHC. The corresponding clinical findings and neonatal outcomes also were recorded. Although no specific histomorphologic changes related to SARS-CoV-2 were noted in the placentas, evidence of maternal-fetal vascular malperfusion was identified, with placentas from SARS-CoV-2-positive women being significantly more likely to show villous agglutination (P = 0.003) and subchorionic thrombi (P = 0.026) than placentas from SARS-CoV-2-negative women. No evidence of direct viral involvement was identified with ISH and IHC. CONCLUSIONS: In this study, third-trimester placentas from SARS-CoV-2-positive women were more likely to show evidence of maternal-fetal vascular malperfusion; however, ISH and IHC provided no evidence of direct viral involvement or vertical transmission.

Ectopic ACTH Syndrome Emerging 5 Years after the Diagnosis of Neuroendocrine Tumor.

Ectopic ACTH syndrome (EAS) arising years after the diagnosis of a neuroendocrine tumor (NET) is exceedingly rare. We describe a case of EAS occurring five years after the diagnosis of a metastatic lung NET in a 61-year-old woman. She presented with severe hypokalemia but was not overtly Cushingoid on exam. Serum cortisol was 61mcg/dL after an overnight 1mg dexamethasone suppression test (<1.8mcg/dL) and urinary free cortisol was 7544 mcg/24h (<45mcg/24h), establishing the diagnosis of Cushing's syndrome. Plasma levels of peptides which have been associated with EAS, Agouti-related peptide (AgRP) and the ACTH precursors POMC (31-kDa) and pro-ACTH (22-kDa), were elevated. Metyrapone was initiated, but hypercortisolism persisted and the patient succumbed to pneumonia shortly after presentation. Retrospective examination of biopsy tissues showed rare ACTH immunoreactivity at the time of initial diagnosis, followed by staining in a greater proportion of cells as the disease progressed, consistent with EAS arising years after the diagnosis of NET. Given the increase in mortality associated with EAS, this unusual case highlights the importance of early detection and raises the possibility that early immunohistochemical stains for ACTH and measurements of ACTH precursors may facilitate the identification of NETs at high risk for EAS.

Extramedullary leukemia behaving as solid cancer: clinical, histologic, and genetic clues to chemoresistance in organ sites.

Recent studies of leukemic tumors in individual extramedullary sites showed they adopt the clinical and metastatic behavior of solid cancers originating in those sites. To elucidate features of leukemic tumors that render them resistant to agents effective against marrow leukemia, we analyzed a series of AML breast tumors by histology, immunohistochemistry, and RNA sequencing. Striking histologic similarities to solid cancers were found: a single-filing architectural pattern virtually identical to that of invasive lobular breast carcinoma and dense desmoplastic keloid-like fibrosis similar to colon, gallbladder, and pancreas carcinomas. Sequencing found 2157 genes significantly downregulated in AML breast tumors compared to normal breast. Comparison to triple-negative breast cancer found 859 genes similarly downregulated. At least 30 of these genes have been associated with poor prognosis in breast cancers. Five were reported in AML marrow studies to correlate with poor prognosis. The findings of this pilot study suggest the seed-and-soil interaction recognized in solid cancer growth may help explain how leukemic cells, in some patients, adopt solid tumor behavior in non-marrow sites. Transformed cells that metastasize from tumor to marrow can impart chemoresistance and be an unrecognized cause of treatment failure and death. Further studies comparing leukemic tumor to simultaneous marrow could potentially identify biomarkers that predict extramedullary resistance and lead to new therapeutic targets. Recognizing the potential for leukemia to adopt solid tumor phenotype, and implementation of body scanning and ablative tumor treatment, could decrease the persistently high rates of marrow resistance and treatment failure.

Cytologic features of needle aspiration of ovarian sex cord tumor with annular tubules: Report of two cases and literature review.

Sex cord tumor with annular tubules (SCTAT) is a rare ovarian tumor with characteristic microscopic morphologic features. Diagnosis most often is based on examination of tissue specimens. Cytologic features of this tumor rarely have been described in the English literature. Herein, we report cytologic findings of cyst aspiration fluid in two cases of SCTAT, with cyto-histologic correlation.

Uterine Carcinosarcomas: Clinical, Histopathologic and Immunohistochemical Characteristics.

Carcinosarcomas (malignant mixed Müllerian tumors or MMMT) are rare malignant tumors in the female genital tract composed of both malignant epithelial and malignant mesenchymal components. They comprise <5% of all neoplasms in the gynecologic tract and have an aggressive clinical course. The purpose of this study is to evaluate the immunophenotype and possible histogenesis of carcinosarcomas of the uterus. Sixty-two cases of uterine carcinosarcomas diagnosed between 1995 and 2011 were retrieved from the gynecologic pathology files at Columbia University Medical Center. Representative tissue blocks containing both epithelial and mesenchymal components were selected from each case for histologic and immunohistochemical studies. Clinical data from each case were retrieved. The epithelial component was poorly differentiated adenocarcinoma in the majority (80.7%) of cases; in 17.7%, the carcinoma was moderately differentiated, and in only 1.6% the carcinoma was well differentiated. 53% of the tumors had homologous stromal elements and 47% displayed heterologous stromal elements. Immunohistochemical study revealed almost equal staining in both epithelial and mesenchymal components of carcinosarcomas for p16 and p53. PAX8 positivity was noted in 73% of epithelial components, but only 13% of stromal components, and PAX8 stromal positivity was never seen in the absence of PAX8 epithelial positivity. Expression of p16, p53, and PAX8 in both malignant components lends support to the monoclonal theory of uterine carcinosarcoma tumorigenesis. The roles of these tumor markers in the diagnosis and pathogenesis of this tumor and associations between clinical characteristics, tumor pathologic features, and prognosis are discussed.

Urinary tract involvement of mantle cell lymphoma diagnosed by urine cytology.

Urinary tract lymphoma is unusual, with the kidney being the most commonly reported site of involvement. Urinary bladder involvement by lymphoma is rare. Mantle cell lymphoma (MCL) is a relatively uncommon type of lymphoma. Herein, we report a case of MCL of the urinary bladder diagnosed by urine cytology, with confirmatory immunocytochemical stains, which has not previously been reported in the literature.

Metastatic tonsillar squamous cell carcinoma masquerading as a pancreatic cystic tumor and diagnosed by EUS-guided FNA.

Metastatic carcinoma to the pancreas is uncommon and head and neck squamous carcinoma metastatic to the pancreas is extremely rare. Metastatic squamous cell carcinoma to the pancreas presents a unique diagnostic challenge: in addition to mimicking the rare primary squamous cell carcinoma of the pancreas based on cytologic, histologic, and immunohistochemical features, it may be mistaken for a cystic neoplasm of the pancreas because of its high predilection for cystic degeneration in metastatic sites. Herein, we report a case of tonsillar squamous cell carcinoma with a cystic pancreatic metastasis diagnosed by ultrasound-guided fine needle aspiration biopsy (EUS-FNA). This represents a third reported case of metastatic squamous cell carcinoma to the pancreas from the head and neck region. Metastatic squamous cell carcinoma should be considered in the differential diagnosis of EUS-FNA during evaluation of pancreatic cystic lesion.

Pneumocystis jirovecii immunostain versus Gomori/Grocott methenamine silver stain of bronchoalveolar lavage in cell blocks: an institutional experience.

INTRODUCTION: Current approaches to Pneumocystis jirovecii (PCJ) screening on bronchioalveolar lavage samples (BAL) include Gomori/Grocott methenamine silver stain (GMS), toluidine blue O stain, Wright-Giemsa stain, immunofluorescent antibody stain, and polymerase chain reaction. Another method available is PCJ immunohistochemistry stain (PCJ IHC). There are no published series evaluating the efficacy of PCJ IHC in cell block preparation of BAL, we sought to compare GMS versus PCJ IHC at our institution. MATERIALS AND METHODS: We performed a retrospective analysis at our institution of all BAL with cell blocks where PCJ IHC and GMS were done simultaneously since March 2015. RESULTS: 982 BAL samples were identified from 640 patients (median age: 54 years; range: 1-84 years). For 895 cases, GMS and PCJ IHC were performed simultaneously. PCJ was identified in 14 samples, from 13 patients (2.2% of patients) using PCJ IHC. GMS stains were read as positive in only 6 of these 14 cases (42.8%); in two of those cases, PCJ was easily identified on routine Papanicolaou stains. We repeated GMS staining on those 14 cases following before-schedule maintenance in our Ventana Benchmark Autostainer, identifying 12 cases positive. In addition, a significantly higher number of organisms was seen on repeat GMS (median: 58) than the original GMS (median: 8.7). Nevertheless, a statistically significant higher number of organisms was detected by PCJ IHC (median: 474). CONCLUSIONS: PCJ IHC performed in cell block is more sensitive and specific than GMS and is a reliable marker when a low number of PCJ organisms are present.

Outbreak of Rapidly Growing Nontuberculous Mycobacteria Among Patients Undergoing Cosmetic Surgery in the Dominican Republic.

Rapidly growing nontuberculous mycobacteria (RG-NTM), which can contaminate inadequately sterilized medical instruments, have been known to cause serious postsurgical skin and soft tissue infections that often are characterized by a prolonged incubation period and a disfiguring clinical course. Historically, these infections have been associated with surgical procedures performed outside the United States. The Centers for Disease Control and Prevention recently reported an outbreak of RG-NTM infections among women who underwent cosmetic surgery in the Dominican Republic. Because of the large Dominican American community in upper Manhattan, we have recently observed a number of these cases at NewYork-Presbyterian Hospital/Columbia University Medical Center. We highlight the case of a 55-year-old woman who developed a postsurgical RG-NTM infection after bilateral breast reduction in the Dominican Republic; she experienced progressive deformity of her left breast until the causative pathogen was identified 20 months after her initial surgery. To assist in the timely diagnosis and treatment of these infections, we aim to promote greater awareness among physicians who are likely to encounter such patients. We present the pathologic findings of a review of 7 cases of RG-NTM infections seen at NewYork-Presbyterian Hospital/Columbia University Medical Center and discuss the diagnostic and therapeutic challenges associated with these infections, such as prolonged incubation periods, the need for acid-fast stains and mycobacterial cultures, and the combination of surgical therapy and lengthy antibiotic courses that are often required for treatment.

Targeted Next-Generation Sequencing Analysis of a Pendred Syndrome-Associated Thyroid Carcinoma.

Pendred syndrome is an autosomal recessive disorder characterized by hearing loss and goiter and is caused by bi-allelic mutations (homozygous or compound heterozygous) of the PDS (SLC26A4) gene. The incidence of Pendred syndrome is 7.5-10/100,000 in the general population, and it carries a 1 % risk of developing thyroid carcinoma. Herein, we report a case of a patient with Pendred syndrome who developed a follicular variant of papillary thyroid carcinoma (FVPTC)-that is approximately at an odd of 1/1,000,000. Targeted next-generation sequencing with ThyroSeq v2 was performed on the tumor, and only a TP53 mutation (TP53 p.R175H) was identified. The mutation was limited to the tumor nodule of FVPTC as shown by immunohistochemistry. This report represents the first extensive molecular study of a Pendred syndrome-associated thyroid carcinoma. The evidences support that thyroid carcinomas arising from dyshormonogenetic goiter require additional genetic alteration in addition to the purported thyroid-stimulating hormone (TSH) overstimulation. It is intrigue to note that the mutant p53 is involved in the development of a low-grade malignant thyroid tumor as FVPTC in this patient.

Cytological features of choricarcinoma in a Pap smear: A case report and literature review.

Choriocarcinoma is an aggressive malignant trophoblastic tumor that mostly occurs during reproductive years. Cytological features of choriocarcinoma in gynecologic Pap smears have not been described. Herein, we report a case of choriocarcinoma in a Pap smear of a patient who had a history of choriocarcinoma with metastatic disease.

Mutations of TSHR and TP53 Genes in an Aggressive Clear Cell Follicular Carcinoma of the Thyroid.

Clear cell follicular carcinoma is a rare type of thyroid cancer and some with aggressive biological behavior. The cytoplasmic clearing of the neoplastic cells has been attributed to the accumulation of various substances, such as glycogen, lipid, mucin, and thyroglobulin, or distension of mitochondria or endoplasmic reticulum. However, the molecular mechanisms responsible for the characteristic appearance of the cell cytoplasm and the biological behavior remain unknown. We report here a case of aggressive clear cell follicular carcinoma of the thyroid with molecular profile using targeted next generation sequencing (NGS) that presented as a metastatic tumor in a woman with a history of breast carcinoma. The NGS data revealed the coexisting of a well-characterized loss-of-function TP53 R248Q mutation and a putative gain-of-function mutation of TSHR L272V, which was suggested by the overexpression of thyroglobulin and SLC5A5 (NIS) genes in this tumor. TP53 mutations are usually related with dedifferentiation, progression, and metastasis of thyroid carcinomas. Identification of TP53 R248Q in this tumor correlated with its aggressive clinical behavior. Gain-of-function mutation of TSHR can overstimulate the thyroid follicular cells as the elevated level of TSH does and might have contributed to the development of clear cell morphology in this tumor. This report represents the first case of clear cell follicular carcinoma of the thyroid with NGS analysis and more molecular characterization is needed to elucidate the pathogenesis and provide more prognosis-relevant information for this uncommon variant of thyroid carcinomas.

Infiltrating adenomyosis of the cervix with features of a low-grade stromal sarcoma: a case report and a literature review.

Adenomyosis is a common, non-neoplastic, chronic gynecologic disorder that is detected in 5% to 70% of hysterectomy specimens. It is characterized by the presence of ectopic endometrial glands and stroma within the myometrium, and it occurs mostly in late reproductive age women. Adenomyosis has a propensity to present in the uterine fundus and is rarely seen in the cervix. At present, the most reliable way to diagnose adenomyosis is by pathologic examination of the hysterectomy specimens. Herein, we report a case of infiltrating adenomyosis in the cervix with unusual clinical and pathologic findings.

Cytological diagnosis of angiosarcoma arising in an immunosuppressed patient 6 years after multi-visceral transplantation: a case report and literature review.

Angiosarcoma is a rare and aggressive malignant tumor of soft tissue. It can arise in almost any part of the body, most commonly in the skin and the superficial soft tissue in the head and neck region. Although the etiology of angiosarcoma is unknown, there are several well-known risk factors, such as chronic lymphedema, exposure to radiation, toxins, and foreign bodies. It rarely occurs in transplant patients. Cytological criteria for the diagnosis of angiosarcoma have not been fully established, having been described only in a few cases, mostly fine-needle aspiration biopsies (FNAB). Herein, we present a case of angiosarcoma arising in an immunosuppressed patient status post multi-visceral transplantation and diagnosed by cytology. To the best of our knowledge, this is the first report of such a case in the English literature. The cytological findings from endoscopic ultrasound-guided FNAB and ascites fluid are discussed.