Metastatic malignant peripheral nerve sheath tumor of the uterus and cervix: Diagnostic Challenges, prognostic determinants and treatment.

•MPNST is an uncommon sarcoma of the nerve sheath that is rarely found in the female reproductive tract.•Preoperative uterine mass imaging should include pelvic MRI and thorough evaluation of imaging by an expert pelvic MRI radiologist.•Metastatic MPNST has a poor prognosis and systemic treatment options lack efficacy.

Mesonephric Adenocarcinoma and Mesonephric-like Adenocarcinoma of the Urinary Tract.

Given the association of mesonephric adenocarcinoma (MA) of the uterine cervix with florid mesonephric hyperplasia, one would expect MAs to rarely arise in other anatomical locations that harbor mesonephric remnants. In contrast, mesonephric-like adenocarcinoma (MLA) is thought to arise from Müllerian origin without an association with mesonephric remnants. The current case series characterizes 4 cases of MA arising in the urinary bladder (1 woman and 3 men), 1 case of MA in the perirenal region (woman), and 1 case of MLA in the ureter (woman). All cases displayed morphologic features similar to MA of the uterine cervix and MLA of the ovary and endometrium, characterized by predominant tubular and focal glandular/ductal architecture. Mesonephric remnants in the bladder wall were closely associated with adjacent MA in cases 1 and 4. MLA in case 6 was associated with mesonephric-like proliferations and endometriosis. All cases (6/6) were diffusely positive for Pax8, and all displayed a luminal pattern of CD10 staining, except case 4 for which CD10 immunostain was not available for review. Gata3 was either focally positive (cases 1, 2, and 6), negative (case 3), or diffusely positive (case 5). TTF-1 was diffusely expressed in cases 1 and 3 and negative in cases 2, 5, and 6. Although a KRAS G12C somatic mutation was detected in case 6, hotspot mutations in KRAS, NRAS, and PIK3CA were not present in other tested cases. Our study demonstrates that MAs and MLAs of the urinary tract share similar histopathogenesis, morphology, and immunophenotype to their counterparts in the female genital tract. We propose that, in the urinary tract, MA might be classified as a distinctive tumor that arises from mesonephric remnants or presumed Wolffian origin if they are not related to Müllerian-type precursors. The tumor displaying similar morphology and immunoprofile to MA but associated with Müllerian-type precursors should be classified as MLA.

Twin/Multiple Gestations With a Hydatidiform Mole: Clinicopathologic Analysis of 21 Cases With Emphasis on Molecular Genotyping and Parental Contribution.

Complete hydatidiform moles (CHMs) and partial hydatidiform moles (PHMs) are abnormal gestations characterized by vesicular chorionic villi accompanied by variable trophoblastic hyperplasia, with or without embryonic development. CHMs are purely androgenetic (only paternal [P] chromosome complements), mostly homozygous/monospermic (~85%) but occasionally heterozygous/dispermic, whereas PHMs are overwhelmingly diandric triploid (2 paternal [P] and 1 maternal [M] chromosome complements) and heterozygous/dispermic (>95%). The presence of a fetus in a molar pregnancy usually indicates a PHM rather than a CHM; however, CHMs and PHMs rarely can be associated with a viable fetus or a nonmolar abortus in twin pregnancies and rare multiple gestation molar pregnancies have been reported. A "one-oocyte-model," with diploidization of dispermic triploid zygotes, has been proposed for twin CHM with coexisting fetus, and a "two-oocyte-model" has been proposed for twin PHM with coexisting fetus. Among 2447 products of conception specimens, we identified 21 cases of twin/multiple gestations with a molar component, including 20 CHMs (17 twins, 2 triplets, 1 quintuplet) and 1 PHM (twin). P57 immunohistochemistry was performed on all; DNA genotyping of molar and nonmolar components was performed on 9 twin CHMs, 1 triplet CHM, 1 quintuplet CHM, and 1 twin PHM. All CHM components were p57-negative and those genotyped were purely androgenetic. Twin CHMs had genotypes of P1M1+P2P2 in 5, P1M1+P1P1 in 1, and P1M1+P2P3 in 1, consistent with involvement of 1 oocyte and from 1 to 3 sperm-most commonly a homozygous CHM but involving 2 sperm in the whole conception-and compatible with a "one-oocyte-model." The triplet CHM was P1M1+P1P1+P2M2 and the quintuplet CHM was P1M1+P2M2+P2M2+P3M3+P4P4, consistent with involvement of 2 sperm and at least 2 oocytes for the triplet and 4 sperm and at least 3 oocytes for the quintuplet. The twin PHM had a P1M1+P2P3M2 genotype, consistent with involvement of 2 oocytes and 3 sperm. p57 immunohistochemistry is highly reliable for diagnosis of CHMs in twin/multiple gestations. Refined diagnosis of molar twin/multiple gestations is best accomplished by correlating morphology, p57 immunohistochemistry, and molecular genotyping, with the latter clarifying zygosity/parental chromosome complement contributions to these conceptions.

Acute abdomen caused by a large solitary jejunal diverticulum that induced a midgut volvulus. Report of a case.

BACKGROUND: Jejunal diverticula are a rare subtype of false diverticula found in the gastrointestinal tract. When present, they are usually multiple, in the proximal jejunum and asymptomatic. Rarely, they can cause acute complications that can develop into an acute abdomen requiring surgical intervention. We present the rare manifestation of a single jejunal diverticulum causing midgut volvulus and bowel ischemia. Early surgical intervention with small bowel derotation allowed complete recovery. METHODS: Data regarding the case, operative intervention, and patient follow-up was prospectively accumulated with permission of the patient at an academic institution. All patient identifiers were removed. All research steps were performed under guidance outlined in the SCARE criteria. RESULTS: We present the case of a 78-year-old man who presented to our institution with an acute abdomen. CT imaging demonstrated a whirlpool sign without an obvious lead point. The patient was without prior surgical intervention. Urgent exploratory laparotomy revealed a midgut volvulus with associated bowel ischemia and impending infarction secondary to adhesive disease from a large single jejunal diverticulum. Derotation resulted in gradual recovery of bowel vascularity. Resection of the portion of the jejunum containing the diverticulum resulted in full clinical recovery of the patient. CONCLUSIONS: Complications of jejunal diverticula, although rare, should be considered as part of the differential diagnosis of an acute abdomen of unknown etiology. Urgent surgical intervention was required to avoid a potential catastrophic outcome.

Correlation of Expression of Breast Biomarkers in Primary and Metastatic Breast Carcinomas: A Single-Institution Experience.

OBJECTIVE: Changes in the status of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) in metastatic breast carcinomas are frequently reported. We examined the change in the status of biomarkers in metastatic breast carcinomas. STUDY DESIGN: This study cohort was composed of 137 metastatic breast carcinomas (58 surgical and 79 cytological specimens) with existing primary tumors during a study period from 2013 to 2015. RESULTS: The overall change rates in metastases were 9, 21 and 6% for ER, PR and HER2, respectively. All changes were from positive in the primary tumor to negative in the metastases. The ER change rate was significantly higher in the cytological than in the surgical metastases. Six of 14 cytological metastases with positive HER2 in primary tumors showed a change in HER2 status, including 5 fluid specimens and 1 fine-needle aspiration (FNA); the other 8 had no change in HER2 status, and included 7 FNAs and 1 fluid specimen. CONCLUSION: The significant percentage of cases with a change in biomarker status supports the recommendation by the College of American Pathologists to test breast biomarkers in metastases. HER2 status change was mostly identified in fluid specimens; however, the small sample size in our cohort and the fact that HER2 fluorescence in situ hybridization was not performed may warrant further studies.

Surgical follow-up results for apocrine adenosis and atypical apocrine adenosis diagnosed on breast core biopsy.

Apocrine adenosis (AA) and atypical apocrine adenosis (AAA) are uncommon findings in breast biopsies that may be misinterpreted as carcinoma. The clinical significance and risk implications of AAA diagnosed on core biopsy are not well established. This study aimed to determine the frequency of carcinoma on follow-up excision in patients with a diagnosis of AA or AAA on core biopsy. Forty-one breast core biopsies of AA (n=29) and AAA (n=12) were identified during a study period of 12 years. Of the 41 core biopsies with AA or AAA, 10 biopsies showed coexisting/concurrent atypical hyperplasia or carcinoma. In the absence of coexisting/concurrent atypical hyperplasia or carcinoma in core biopsy, none of the follow-up excision specimens after a diagnosis of AA or AAA showed ductal carcinoma in situ or invasive carcinoma. In conclusion, AA or AAA by itself is an uncommon core biopsy diagnosis that may not require surgical excision.

Placental site trophoblastic tumor: Immunohistochemistry algorithm key to diagnosis and review of literature.

•Histologic morphology is frequently equivocal for PSTTs.•Histology combined with immunohistochemical staining was necessary to make the diagnosis.•PSTT confined to the uterus was successfully treated with surgery alone.

Bright-field HER2 dual in situ hybridization (DISH) assay vs fluorescence in situ hybridization (FISH): focused study of immunohistochemical 2+ cases.

OBJECTIVES: To compare the INFORM HER2 bright-field dual in situ hybridization (DISH) DNA probe cocktail assay with the PathVysion fluorescence in situ hybridization (FISH) assay on 103 invasive breast carcinomas with a 2+ score on immunohistochemistry (IHC). METHODS: The cases were categorized as positive, equivocal, or negative for HER2 gene amplification using the 2007 American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) HER2:CEP17 ratio criteria and also based on mean HER2 gene copies/cell. The third criterion used a HER2:CEP17 ratio of 2 to categorize cases as positive or negative. RESULTS: The agreement between FISH and DISH was 85% using the 2007 ASCO/CAP ratio criterion, 79% using the mean HER2 gene copies/cell criterion, and 92% using the 2.0 cutoff HER2:CEP17 ratio criterion. In addition, 20 known IHC 3+ breast carcinomas analyzed by DISH showed clusters of the HER2 gene consistent with unequivocal amplification. CONCLUSIONS: Despite some technical and interpretational issues associated with DISH, it compares favorably with FISH in this group of challenging breast cancer cases.

Breast Mass and Lytic Bone Lesions: A Rare Presentation of Non-Hodgkin's Lymphoma Arising in the Breast.

Background. Primary breast lymphoma is a rare malignancy representing less than 1% of all tumors presenting in the breast. Case Presentation. A 55-year-old woman presented with altered mental status due to severe hypercalcemia and was found to have a large breast mass with lytic bone lesions in the calvarium of the skull. Biopsy of the mass revealed diffuse large B-cell lymphoma. Staging workup did not reveal any visceral organ or distant lymph node involvement. The patient's bone marrow biopsy was positive for involvement with lymphoma. Interestingly, the patient also had a non quantifiable IgA kappa monoclonal protein in the serum. Conclusion. Here, we describe a common presentation in medical oncology, that is, a patient presenting as a clinically advanced breast tumor with hypercalcemia from lytic bone lesions. However, diagnostic workup led to the diagnosis of another common malignancy in an uncommon location, namely, diffuse large B-cell lymphoma arising in the breast.

Clinicopathologic study of serous tubal intraepithelial carcinoma with invasive carcinoma: is serous tubal intraepithelial carcinoma a reliable feature for determining the organ of origin?

In the past several decades, the concept of serous ovarian carcinoma has been revised repeatedly. However, the exact pathogenesis remains controversial. The most popular current concept is origin from the epithelium of the fimbriated ends of the fallopian tubes. The objective of our study was to evaluate the characteristic clinical and morphologic features of serous tubal intraepithelial carcinoma (STIC) and associated invasive carcinomas. One hundred sixteen consecutive cases of STIC seen from 2007 to 2011 were included in this study. High-grade serous carcinoma (HGSC) with or without a mixed component was identified in 107 cases (92.2%), non-HGSC in 5 cases, and STICs without invasive carcinoma in 4 cases. Using conventional criteria, HGSCs were classified as fallopian tube in origin in 65 cases (60.7%), as ovarian in 30 (28.0%), as peritoneal in 9 (8.4%), and as endometrial in 3 (2.8%). Among the 107 cases with HGSCs, most STICs (86; 80%) were present unilaterally, whereas invasive tumors more commonly involved the ovaries bilaterally (79%; 84 cases). These findings support the hypothesis that STIC acts as a precursor lesion for most fallopian tube, ovarian, and peritoneal HGSCs, but not for endometrial HGSC.

Is PAX2 a reliable marker in differentiating diffuse malignant mesotheliomas of peritoneum from serous carcinomas of müllerian origin?

Diffuse peritoneal malignant mesotheliomas (DPMM) are often disseminated in the peritoneal cavity as multiple nodules including localized masses in the ovaries that are clinically and histologically similar to serous adenocarcinomas of müllerian origin. It is imperative to differentiate these tumors given their diverse responses to chemotherapy and/or radiotherapy. PAX2 gene was recently demonstrated in benign epithelial cells of the female genital tract and in serous carcinomas (SC) of müllerian origin. The aim of our study was to determine if PAX2 can reliably be used in differentiating DPMM from SC. A total of 59 cases to include 25 cases of DPMM and 34 cases of SC were retrieved. All cases were stained with PAX2, Wilm tumor gene 1, calretinin and the results were compared. Our results demonstrate that PAX2 can be used reliably as a Müllerian marker in formulating an efficient panel to differentiate DPMM and SC.

Histopathologic follow-up and human papillomavirus DNA test results in 290 patients with high-grade squamous intraepithelial lesion Papanicolaou test results.

BACKGROUND: The study documents histopathologic outcomes and high-risk (hr) human papillomavirus (HPV) test results in a large cohort of patients with high-grade squamous intraepithelial lesion (HSIL) liquid-based cytology (LBC) Pap test results. METHODS: A total of 352 patients with HSIL results (338 cervical and 14 vaginal) who had hrHPV testing and 290 patients with biopsy follow-up were studied. hrHPV detection rates were compared at different ages, with or without an endocervical/transformation zone sample (EC/TZS), and for cervical and vaginal HSIL Pap smears. Histopathologic follow-up findings were also compared. hrHPV-negative HSIL slides were re-evaluated in a blinded manner. RESULTS: A total of 325 of 338 (96.2%) cervical HSIL and 12 of 14 (87.5%) vaginal HSIL tested hrHPV-positive. A total of 271 of 281 (96.4%) EC/TZS-positive cervical HSIL and 54 of 57 (94.7%) EC/TZS-negative cervical HSIL tested hrHPV-positive. The percentage of hrHPV-positive HSIL declined slightly with increasing age. 197 of 273 (72.3%) hrHPV-positive cervical HSIL had histopathologic cervical intraepithelial neoplasia (CIN) 2/3+ follow-up, including 8 squamous carcinomas, compared with 4 of 12 (33.3%) hrHPV-negative HSIL with CIN2/3 (no carcinomas). 167 of 241 (69.2%) EC/TZS-positive HSIL had CIN2/3+ follow-up, compared with 34 of 44 (77.3%) EC/TZS-negative HSIL. Equivocal HSIL morphology characterized some HPV-negative HSIL without CIN2/3+ follow-up. CONCLUSIONS: hrHPV was detected in LBC vials from 96.2% of 338 cervical HSIL and 85.7% of 14 vaginal HSIL. CIN2/3+ was significantly more likely with hrHPV-positive cervical HSIL than with hrHPV-negative cervical HSIL. Presence or absence of an EC/TZS did not significantly impact HSIL hrHPV or CIN2/3+ rates. Some hrHPV-negative HSIL cases may represent HSIL cytologic mimics.

Cytomorphology of crystal storing histiocytosis in the breast associated with lymphoma: a case report.

Crystal storing histiocytosis (CSH) is a very rare immunoglobulin (Ig) deposition disorder in which macrophages accumulate light chains or Ig crystalline inclusions. It is frequently associated with lymphoproliferative disorders, but can be seen in some reactive conditions too. This article reports the cytomorphologic, histopathologic, and ancillary study findings of a marginal zone B cell lymphoma of the breast with CSH in a 54-year-old woman. To the best of our knowledge, this is the first report describing CSH in the breast and one of a few reports describing the cytomorphology of CSH. In breast fine-needle aspiration biopsies, CSH can be confused with benign processes such as fat necrosis and histiocytic lesions. Thus, awareness of this rare entity and its frequent association with lymphoproliferative disorders is useful in order to triage a specimen appropriately and exclude the possibility of a lymphoproliferative process.

Clinical importance of histologic grading of lobular carcinoma in situ in breast core needle biopsy specimens: current issues and controversies.

Lobular carcinoma in situ (LCIS) is considered a risk factor for development of invasive carcinoma (IC). Many variants of LCIS have been described based on pathologic features such as nuclear grade, pleomorphism, and necrosis, but little is known about the biology of these variants. The proposed 3-tier grading system for LCIS has not been validated or endorsed across laboratories. We found significant upstaging of pure pleomorphic LCIS (LCIS with nuclear grade [NG] 3), up to 25% in core needle biopsy (CNB) specimens, in an earlier study. The aim of the current study was to address the importance of pure classical LCIS (NGs 1 and 2) in CNB specimens along with clinicopathologic follow-up. In follow-up resection specimens, IC or ductal carcinoma in situ was seen in 18% (7/39), a high incidence of residual LCIS was seen in 69% (27/39), and other high-risk lesions, such as atypical ductal hyperplasia, were seen in 36% (14/39) of LCIS NG 2 cases. Our study illustrates the importance of grading LCIS; we recommend follow-up excision in LCIS NG 2 cases owing to a high incidence of residual LCIS and the likelihood of identifying other high-risk lesions.