Vesicular Nuclei Research Articles

Lymphoepithelioma-like carcinoma of the skin

Primary cutaneous lymphoepithelioma-like carcinoma is a rare disease with low metastatic potential. Its morphologic and pathological features are similar to those of nasopharyngeal lymphoepithelial carcinoma. We report the case of a 60-year-old man with an infrapalpebral pearly papule, measuring 0.6 cm in diameter. The lesion was excised with a clinical hypothesis of basal cell carcinoma or squamous cell carcinoma. Histopathological analysis revealed a malignant neoplasm with syncytial arrangement of cells with vesicular nuclei, associated with dense lymphocytic infiltrate. Immunohistochemistry revealed cytokeratin-positive cells (AE1/AE3) and p63 protein, indicating epithelial histogenesis and squamous differentiation. A negative Epstein-Barr virus test result was achieved by immunohistochemistry. Primary lymphoepithelioma-like carcinoma of the skin is a differential diagnosis of lesions with prominent inflammatory infiltrates.

Analysis of DNA methylation and microRNA expression in NUT (nuclear protein in testis) midline carcinoma of the sinonasal tract: a clinicopathological, immunohistochemical and molecular genetic study.

The aim of this study was a detailed clinicopathological investigation of sinonasal NUT midline carcinoma (NMC), including analysis of DNA methylation and microRNA (miRNA) expression. Three (5%) cases of NMC were detected among 56 sinonasal carcinomas using immunohistochemical screening and confirmed by fluorescence in situ hybridization. The series comprised 2 males and 1 female, aged 46, 60, and 65 years. Two tumors arose in the nasal cavity and one in the maxillary sinus. The neoplasms were staged pT1, pT3, and pT4a (all cN0M0). All patients were treated by radical resection with adjuvant radiotherapy. Two patients died 3 and 8 months after operation, but one patient (pT1 stage; R0 resection) experienced no evidence of disease at 108 months. Microscopically, all tumors consisted of infiltrating nests of polygonal cells with vesicular nuclei, prominent nucleoli and basophilic cytoplasm. Abrupt keratinization was present in only one case. Immunohistochemically, there was a diffuse expression of cytokeratin (CK) cocktail, CK7, p40, p63, and SMARCB1/INI1. All NMCs tested negative for EBV and HPV infection. Two NMCs showed methylation of RASSF1 gene. All other genes (APC, ATM, BRCA1, BRCA2, CADM1, CASP8, CD44, CDH13, CDKN1B, CDKN2A, CDKN2B, CHFR, DAPK1, ESR1, FHIT, GSTP1, HIC1, KLLN, MLH1a, MLH1b, RARB, TIMP3, and VHL) were unmethylated. All NMCs showed upregulation of miR-9 and downregulation of miR-99a and miR-145 and two cases featured also upregulation of miR-21, miR-143, and miR-484. In summary, we described three cases of sinonasal NMCs with novel findings on DNA methylation and miRNA expression, which might be important for new therapeutic strategies in the future.

Utility of Cytokeratin7 Immunocytochemistry in the Cytopathological Diagnosis of Fibrolamellar Hepatocellular Carcinoma.

Objective:To distinguish fibrolamellar hepatocellular carcinoma (FL-HCC) variant from the conventional hepatocellular carcinoma (HCC) by cytology, immunocytochemistry, and morphometry.Study Design:Retrospective detailed cytomorphological, immunocytochemical, and morphometric analysis was performed in 6 cases of FL-HCC reported on fine needle aspiration. Cell block immunocytochemistry (CB-ICC) for CK7 and CD68 was performed in four cases. Morphometry was carried out with Cell A software. Area of the cell, nucleus and nucleolus was measured in 50 nuclei per case in 6 cases each of FL-HCC and HCC.Results:The mean age of patients with FL-HCC was 19 years and all had normal serum alpha-fetoprotein levels. Fine needle aspiration smears showed large polygonal cells with abundant cytoplasm, vesicular nucleus and prominent nucleolus, associated with variably cellular fibrous stromal fragments. Intranuclear inclusions, cytoplasmic eosinophilic inclusions, and bile were also noted. FL-HCC showed strong membrano-cytoplasmic CK7 positivity and cytoplasmic granular and canalicular positivity for CD68. In contrast, HCC showed weak focal positivity for CK7 and only canalicular CD68 positivity. Morphometry revealed that FL-HCC cells were 2.19 times the size of HCC.Conclusion:CK7 immunocytochemistry on cell blocks is useful for confirming and distinguishing it from HCC.

Microscopic Anatomy of Sertoli and Leydig Cells During Fetal Development in Baladi Rabbit

Fifty three baladi rabbit embryos and fetuses were used in this study. The results revealed that the testicular differentiation occurred with the formation of the testicular cords with their constituents, gonocytes and primitive Sertoli cells at the 18^th day postconception. The Sertoli cells were increased in number from 20^th day postconception onwards and they appeared as small sized cells with oval darker nuclei. The Leydig cells were demonstrated at the 20^th day of gestation life as clusters of polyhedral large cells with strongly acidophilic finely granular cytoplasm and large, vesicular, spherical and eccentric nuclei. At 28^th day postconception up to the full term rabbit fetus, the Leydig cells of the testis showed a marked reduction in size and number.

Effect of Inhalation of Formaldehyde on the Structure of Hippocampus of Albino Rat and the Possible Protective Role of Omega-3

ABSTRACTBackground: Formaldehyde (FA) is a vastly used chemical structure with which every physician had a first-hand experience in his early days of training in the anatomy laboratory. The National Institute of Occupational Safety and Health listed 52 occupations that expose people to FA. Omega-3 polyunsaturated fatty acids (PUFAs) are important for brain development and performance especially in the hippocampus. They improve spatial and long term memory and learning functions, enhance synaptogenesis and boost hippocampal neurite development.Aim of work: To investigate the effect of exposure to FA vapor on the structure of hippocampus and to study the possible protective role of Omega-3.Material and Methods: Rats were divided into three groups; each group was composed of eight rats. Group I: used as control. Group II: rats were exposed to 10% FA for 6 hours/ day, every other day for 6 weeks. Group III: rats were exposed to 10% FA for 6 hours/ day, every other day for 6 weeks; simultaneously Omega-3 was given orally as 300 mg/kg body weight daily throughout the 6 weeks. At the end of the experiment, the rats were anaesthetized, brains dissected and specimens were processed for light microscopy.Results: Histological study indicated that in FA exposed group, some regions of cornu Ammonis (CA) showed pyramidal cells with large rarefied lightly stained nuclei while other regions showed degenerated pyramidal cells. Pyknotic small deeply stained nuclei were also noticed. Oligodendrocytes were seen in close relation to some of the degenerated cells. Neuronal processes were broken, replaced by vacuolated swollen elongated spaces. Ramifying processes of the astrocytes were extensively seen extending in-between the pyramidal cells and also in the molecular and polymorphic layers as well. Occasional apoptotic cells were seen. In Omega treated group, pyramidal cells appeared large triangular with large vesicular nuclei and prominent nucleoli. However, few pyramidal cells showed vacuolation and degeneration of the cytoplasm, their nuclei were deeply stained and were either irregular or shrunken small pyknotic. Few oligodendrocytes were seen encroaching and settling close to some pyramidal cells. Some apical dendrites preserved their integrity being directed towards the molecular layer. In addition, no apoptotic cells could be detected. In statistical results, in group exposed to FA, there was a significant decrease in pyramidal cell count compared to control group and non-significant decrease compared to Omega group. Also, there was a significant decrease in pyramidal layer thickness compared to control and Omega groups.Conclusion: FA exposure may have serious effects on human hippocampal structure, if exposure to formaldehyde is inevitable, it is advised to use a protective antioxidant such as Omega-3 simultaneously which may diminish the hazardous effect of FA on the hippocampal structure and function.

Hodgkins Lymphoma in a Child with Sickle Cell Anaemia: A Case Report

To study the co existence of Hodgkins lymphoma in sickle cell disease in a 10-year-old boy who is also a known case of sickle cell anaemia presented to out centre with symptoms of fever, weight loss. History of previous blood transfusions was given. On clinical examination, he was found to have pallor, generalised lymphadenopathy, splenomegaly. Complete blood picture revealed haemoglobin of 9 g/dl, white blood cell count of 12,000/cu mm, platelet count of 2 lakhs. Biopsy from the cervical lymph node revealed effacement of lymph nodal architecture with replacement by scattered atypical mononuclear and binucleate Reed–Sternberg cells with moderate cytoplasm, large vesicular nucleus and prominent eosinophilic nucleoli against a background of, mixed population of small lymphocytes, plasma cells and few eosinophils. Immuno histochemistry revealed positive expression of CD15, CD30, Pax-5 in the atypical cells and thus proved to be Hodgkins lymphoma.

Nuclear and cytoplasmic features in the diagnosis of Clark's nevi.

Interpretation of Clark's nevi has generated debate over the years; although criteria have been proposed for grading morphological features of melanocytes, there is still confusion and variability in the assessment of these lesions. This is a retrospective observational study conducted on 100 Clark's nevi and 84 melanomas. A single expert dermatopathologist evaluated all blinded and randomized photomicrographs of both the Clark's nevi and melanomas for the presence of 14 cytologic features. Subsequently, a multivariate model was used to obtain sensitivity and specificity. Clark's nevi showed a significantly higher frequency of absent-or-inconspicuous nucleoli over melanoma, whereas mitotic figures, pleomorphism, notching, multiple nucleoli, peppered moth nuclear pattern, flattened adjacent nuclei, prominent nucleoli and vesicular nucleus with rounded nucleoli were found significantly higher in frequency in melanomas. Our data suggest that nuclear alterations are of value in the differentiation of atypical nevi from melanoma.

SMARCB1-deficient Tumors of Childhood: A Practical Guide.

The SMARCB1 gene ( INI1, BAF47) is a member of the SWItch/Sucrose Non-Fermentable (SWI/SNF) chromatin remodeling complex, involved in the epigenetic regulation of gene transcription. SMARCB1 acts as a tumor suppressor gene, and loss of function of both alleles gives rise to SMARCB1-deficient tumors. The prototypical SMARCB1-deficient tumor is the malignant rhabdoid tumor (MRT) which was first described in the kidney but also occurs in soft tissue, viscera, and the brain (where it is referred to as atypical teratoid rhabdoid tumor or AT/RT). These are overwhelmingly tumors of the very young, and most follow an aggressive and ultimately lethal course. Morphologically, most but not all contain a population of "rhabdoid" cells, which are large cells with abundant cytoplasm, perinuclear spherical inclusions, and eccentric vesicular nuclei with large inclusion-like nucleoli. MRT immunohistochemistry reveals complete loss of SMARCB1 nuclear expression, and molecular analysis confirms biallelic SMARCB1 inactivation in the vast majority. Rare AT/RTs have loss of SMARCA4, another SWI/SNF member, rather than SMARCB1. With the widespread adoption of SMARCB1 immunohistochemistry, an increasing number of SMARCB1-deficient tumors outside of the MRT-AT/RT spectrum have been described. In addition to MRT and AT/RT, pediatric tumors with complete loss of SMARCB1 expression include cribriform neuroepithelial tumor, renal medullary carcinoma, and epithelioid sarcoma. Tumors with variable loss of SMARCB1 expression include subsets of epithelioid malignant peripheral nerve sheath tumor, schwannomas arising in schwannomatosis, subsets of chordomas, myoepithelial carcinomas, and sinonasal carcinomas. Variable and reduced expression of SMARCB1 is characteristic of synovial sarcoma. In this review, the historical background, clinical characteristics, morphology, immunohistochemical features, and molecular genetics most germane to these tumors are summarized. In addition, familial occurrence of these tumors (the rhabdoid tumor predisposition syndrome) is discussed. It is hoped that this review may provide practical guidance to pathologists encountering tumors that have altered expression of SMARCB1.

Prostate carcinoma with amphicrine features: further refining the spectrum of neuroendocrine differentiation in tumours of primary prostatic origin?

The current World Health Organization classification categorises high-grade neuroendocrine (NE) carcinomas of the prostate into small-cell and large-cell types. A distinct form of carcinoma showing synchronous dual exocrine and NE differentiation, termed amphicrine carcinoma, has been described at various other sites, primarily within the gastrointestinal tract. The aim of this study was to investigate the clinicopathological features of a series of metastatic prostate carcinoma (PCa) cases with amphicrine features. Five cases of high-grade PCa showing an amphicrine immunohistochemical phenotype were prospectively collected. The serum prostate-specific antigen (PSA) level at diagnosis ranged from 38 ng/ml to 992 ng/ml (median 200 ng/ml). All five patients had metastatic disease, four at initial presentation. Microscopically, the tumours showed a solid/nested growth pattern composed of cells with amphophilic cytoplasm, vesicular nuclei, and macronucleoli. Morphological features of small-cell or large-cell NE carcinoma were absent. As compared with conventional high-grade PCa, the tumour cells showed a higher level of nuclear pleomorphism, brisk mitotic activity, and a high Ki67 proliferation index (median 50%). All cases showed immunohistochemical positivity for PSA, androgen receptor, and prostate-specific acid phosphatase, combined with diffuse or confluent/non-focal positivity for chromogranin-A and synaptophysin. Two hormone-naive cases showed a clinical response to androgen deprivation therapy. This series highlights a previously undefined, clinically aggressive variant of PCa showing dual exocrine and NE differentiation, for which we are proposing the term PCa with amphicrine features. Increased recognition of these tumours may lead to a better understanding of their biology, and ultimately improve their clinical management.

Combined Adenosquamous and Large Cell Neuroendocrine Carcinoma of the Gallbladder.

Large cell neuroendocrine carcinoma (LCNEC) of the gallbladder is extremely rare and usually combined with other type of malignancy, mostly adenocarcinoma. We report an unusual case of combined adenosquamous carcinoma and LCNEC of the gallbladder in a 54-year-old woman. A radical cholecystectomy specimen revealed a 4.3×4.0 cm polypoid mass in the fundus with infiltration of adjacent liver parenchyma. Microscopically, the tumor consisted of two distinct components. Adenosquamous carcinoma was predominant and abrupt transition from adenocarcinoma to squamous cell carcinoma was observed. LCNEC showed round cells with large, vesicular nuclei, abundant mitotic figures, and occasional pseudorosette formation. The patient received adjuvant chemotherapy. However, multiple liver metastases were identified at 3-month follow-up. Metastatic nodules were composed of LCNEC and squamous cell carcinoma components. Detecting LCNEC component is important in gallbladder cancer, because the tumor may require a different chemotherapy regimen and show early metastasis and poor prognosis.

Diffuse Large B-Cell Lymphoma Presenting as a Pancreatic Mass

Primary lymphomas of the gastrointestinal tract are rare; however is the most common site of extranodal involvement. When presenting as a primary lesion, a distinction from an epithelial malignancy is critical given the difference in therapy and prognosis. Primary pancreatic lymphomas represent cancer. On physical exam, he looked chronically ill, had pale conjunctiva, tenderness to palpation in epigastric area,and palpable inguinal lymphadenopathy. Initial CBC, chemistries and liver function tests were unremarkable. LDH was elevated and CA19-9 level was normal. An abdominal CT revealed a pancreatic tail mass measuring 3.1 x 2.3 cm associated with duodenal wall thickening, peripancreatic, supraclavicular, mediastinal and inguinal lymphadenopathy. Also, a cardiac intraventricular mass that measured 6.3 x 4cm was seen occluding almost all the right ventricle.Important to note is that the liver was unremarkable. A PET CT scan showed multiple FDG-avid lesions including the pancreatic tail and cardiac masses, with a foci of highest tracer uptake near the duodenum. An ultrasound guided biopsy of a neck nodule for immunohistochemistry showed large cells with vesicular nuclei and prominent nucleoli; the cells stained positive for CD20, CD45, suggesting diffuse large B-cell lymphoma (DLBCL). He received rituximab,cyclophosphamide, doxorubicin, vincristine, prednisone, and entecavir.Figure: Pancreatic tail mass approximately 3.1 x 2.3cm.Figure: There is a foci of severe high tracer uptake of the pancreas.Figure: Multiple hypermetabolic lesions are evident.After completion of first course, he was discharged home. While at home he developed gastrointestinal bleeding that required hospitalization. At that time and while his performance status declined, he refused further treatment. This case shows that a distinction between DLBCL and pancreatic adenocarcinoma is challenging but extremely important since treatment and prognosis are very different. This patient presented with abdominal symptoms and radiologic evidence of a pancreatic mass with regional and distant lymphadenopathy initially suggesting a primary pancreatic neoplasm. However, the absence of liver metastases, B symptoms, cardiac involvement and the extensive lymphadenopathy suggested a lymphoproliferative disease. The early suspicion of this rare presentation of Non-Hodgkin's lymphoma involving the pancreas, duodenum and right ventricle helped establish timely and appropriate therapy given the high mortality associated with this disease.

SMARCB1/INI1 Loss in Epithelioid Schwannoma

The epithelioid variant of schwannoma is rare, and loss of SMARCB1/INI1 expression has been observed in a subset of cases. Our aim was to further define the clinicopathologic features and to evaluate SMARCB1/INI1 deficiency in a large cohort of 65 epithelioid schwannomas diagnosed between 2002 and 2015, which consisted of 32 men and 33 women with median age at diagnosis of 45 years (range, 13 to 75 y). Most tumors arose in the extremities (upper, 20, lower, 15) and trunk (17); 9 were visceral (8 gastrointestinal). Most somatic tumors were in dermis/subcutis (53/54) and encapsulated (53/54) with an epithelial membrane antigen-positive perineurial capsule in 46 cases; visceral tumors were unencapsulated. No patients were reported to have any neurocristopathy. Three patients had multiple lesions (2 each). Tumor size range was 0.4 to 22.7 cm (median, 1.2 cm). Tumors showed multilobulated growth of uniform epithelioid cells in sheets and nests or singly dispersed within a frequently myxoid or hyalinized stroma. Tumor cells had round vesicular nuclei and abundant palely eosinophilic cytoplasm, usually lacking significant pleomorphism or hyperchromasia. Some tumors showed foci resembling conventional schwannoma (spindled morphology, 29; Antoni B foci or Verocay bodies, 8; hyalinized thick-walled vessels, 16). Mitoses ranged from 0 to 9 per 10 high-power fields (median count, 1). No tumor had necrosis. Twenty-three cases showed degenerative nuclear atypia. Focally striking cytologic atypia was present in 7 tumors, 3 of which showed transformation to epithelioid malignant peripheral nerve sheath tumor. All tumors showed diffuse positivity for S-100 protein and consistent positivity for SOX10 (50/50), while INI1 expression was lost in 24 of 57. Other positive immunohistochemical results were: glial fibrillary acidic protein (15/37) and focal keratin (2/40); epithelial membrane antigen (0/53) and melanocytic markers were negative (Mart-1 0/29; HMB-45 0/23). Most patients underwent local excision (13 complete; 47 marginal/positive margins). Follow-up data available for 31 patients (range, 1 to 108 mo; median, 37) indicated that no patient had developed metastatic disease, including 3 cases with cytologic atypia, one of which showed malignant transformation. One tumor without atypia developed local recurrence 48 months after marginal excision; all other patients were alive with no evidence of disease. Epithelioid schwannoma most commonly occurs as a superficial tumor on the extremities or trunk in adults. Loss of SMARCB1/INI1 expression is seen in 42% of tumors. Tumors follow a generally benign clinical course, although recurrence and malignant transformation are infrequent. Some tumors are characterized by notable cytologic atypia, the significance of which is uncertain but which may indicate a morphologic continuum with low-grade epithelioid malignant peripheral nerve sheath tumor.

The clinical features of epithelioid hemangioendothelioma in a Han Chinese population: A retrospective analysis.

Epithelioid hemangioendothelioma (EHE) is a rare indolent vascular tumor which occurs at liver, lung, bone, and so on. However, the etiology of EHE is evasive.These patients were enrolled at the First Affiliated Hospital of Xi’an Jiaotong University from January 2011 to December 2015. Retrospective analysis is done by demographic data of clinical manifestations, laboratory parameters, CT imaging, histological, and immunohistochemical features in 9 cases in Shaanxi.Of the patients, 8 were females (88.9%) and 1 were males (11.1%). The age ranged from 34 to 71 years (mean 49 years; median 49 years). Anatomical sites of primary lesions were as follows: liver (n = 6, 66.7%), upper extremities (n = 1, 11.1%), sublingual gland (n = 1, 11.1%), and spine (n = 1, 11.1%). Metastatic disease was diagnosed in 5 cases (55.6%) with occurrence in lung (n = 4, 44.4%), bone (n = 2, 22.2%), upper extremities (n = 1, 11.1%), pleura (n = 1, 11.1%), and spleen (n = 1, 11.1%). Tumor size ranged from 0.5 to 6.8 cm (mean 3 cm). The most tumors were composed of highly cellular areas with small and prominent nucleoli in vesicular nuclei, and ERG (100%) was the most frequently positive in these cases, followed by CD31 (88.9%) and CD34 (77.8%) via histology and immunohistochemistry techniques.EHE is a very rare in Shaanxi. It is significant to find its clinical, radiological, and pathological characters, helping for EHE early diagnosis and treatment, reducing misdiagnosis and improving life quality.

An optimized image analysis algorithm for detecting nuclear signals in digital whole slides for histopathology.

Nuclear estrogen receptor (ER), progesterone receptor (PR) and Ki-67 protein positive tumor cell fractions are semiquantitatively assessed in breast cancer for prognostic and predictive purposes. These biomarkers are usually revealed using immunoperoxidase methods resulting in diverse signal intensity and frequent inhomogeneity in tumor cell nuclei, which are routinely scored and interpreted by a pathologist during conventional light-microscopic examination. In the last decade digital pathology-based whole slide scanning and image analysis algorithms have shown tremendous development to support pathologists in this diagnostic process, which can directly influence patient selection for targeted- and chemotherapy. We have developed an image analysis algorithm optimized for whole slide quantification of nuclear immunostaining signals of ER, PR, and Ki-67 proteins in breast cancers. In this study, we tested the consistency and reliability of this system both in a series of brightfield and DAPI stained fluorescent samples. Our method allows the separation of overlapping cells and signals, reliable detection of vesicular nuclei and background compensation, especially in FISH stained slides. Detection accuracy and the processing speeds were validated in routinely immunostained breast cancer samples of varying reaction intensities and image qualities. Our technique supported automated nuclear signal detection with excellent efficacy: Precision Rate/Positive Predictive Value was 90.23 ± 4.29%, while Recall Rate/Sensitivity was 88.23 ± 4.84%. These factors and average counting speed of our algorithm were compared with two other open source applications (QuPath and CellProfiler) and resulted in 6-7% higher Recall Rate, while 4- to 30-fold higher processing speed. In conclusion, our image analysis algorithm can reliably detect and count nuclear signals in digital whole slides or any selected large areas i.e. hot spots, thus can support pathologists in assessing clinically important nuclear biomarkers with less intra- and interlaboratory bias inherent of empirical scoring. © 2017 International Society for Advancement of Cytometry.

BCOR-CCNB3 Undifferentiated Sarcoma-Does Immunohistochemistry Help in the Identification?

Recent methodology has enabled the identification of some new genetic subgroups within the melting pot of lesions presently classified by the 2013 WHO classification as "undifferentiated/unclassified sarcomas". One of these subgroups is characterized by a paracentric inversion of the X chromosome with consequent formation of a BCOR-CCNB3 fusion. Clinical and pathological features of these tumors overlap with the Ewing sarcoma family as well as other soft tissue sarcomas, thus making them difficult to diagnose. To investigate the morphological and immunohistochemical characteristics of BCOR-CCNB3 positive sarcoma, we reviewed two sarcoma series, comprising 632 and 121 cases. The 11 tumors harboring the BCOR-CCNB3 fusion, identified by CCNB3 immunohistochemistry and/or RT-PCR, were reevaluated for morphological characteristics and further immunohistochemical investigations for CCNB3, SATB2, and Pax8 were performed. Tumors harboring a BCOR-CCNB3 fusion (11/753) occured exclusively in males, with a mean age at diagnosis of 12.9 years, and were mainly axially located. In this group of either spindled or round cell tumors, vesicular nuclei with finely dispersed chromatin, inconspicuous nucleoli and an arciform vascular pattern were pathognomonic. More than 50% of cases stained positive for SATB2 and Pax8, raising the hypothesis of a potential use of these markers in the identification of BCOR-CCNB3 positive undifferentiated/unclassified sarcomas. CCNB3 was confirmed as a useful ancillary immunohistochemical marker.

Epithelioid sarcoma with mesothelial and lymphatic endothelial differentiation: a clinicopathologic analysis of 10 cases

Objective: To investigate the multidirectional differentiation potential in epithelioid sarcoma (ES), with special emphasis on its mesothelial and lymphatic endothelial markers expression. Methods: Ten cases of distal-type ES were included. The clinical, histological, and immunohistochemical(including mesothelial and lymphatic endothelial markers expression)features and follow-up data were evaluated. Results: The patients aged between 8 to 66 years. Five cases were male and five were female. The tumors were located at the palm (2 cases), wrist (3 cases), upper arm (2 cases), poplitealfossa (1 case), lower leg (1 case) and thigh (1 case), respectively. Clinically, most cases presented as painful, firm subcutaneous nodules. Histologically, the tumors were mainly composed of epithelioid, rhabdoid, spindle, or transitional cells, with abundant eosinophilic cytoplasm, oval and vesicular nucleus, and one or more prominent nucleoli. They were arranged in nodular, diffuse nodular or sheet like growth patterns, frequently with necrosis at the center with vague granulomatous configuration. Immunohistochemically, all tumors expressed cytokeratins, epithelial membrane antigen, CD34, desmin, mesothelial markers such as Calretinin, WT1, D2-40, M2A, vascular and lymphatic endothelial markers FLI-1, and VEGFR-3. The tumor cells did not express CD31, FⅧRAg, HHF35, HMB45, Melan A, MyoD1, myogenin, S-100 protein and SMA. All 10 patients underwent radical resection or extended excision, with additional radiotherapy or chemotherapy. During the follow-up from October 2012 to August 2016, seven cases showed recurrences and metastases within 2 months to 2 years. Five patients died of the disease due to widespread metastases. Conclusions: ES may show a wide spectrum of morphology, and display a multidirectional differentiating capabilities including towards mesothelial and lymphatic endothelial cells. As such, its diagnosis and differential diagnosis are particularly important as it is easily confused with other tumors with similar morphology or immune phenotype.

Regeneration of thyroid follicles from primordial cells in a murine thyroidectomized model

The functional unit of the thyroid gland, the thyroid follicle, dynamically responds to various stimuli to maintain thyroid hormone homeostasis. However, thyroid follicles in the adult human thyroid gland have a very limited regenerative capacity following partial resection of the thyroid gland. To gain insight into follicle regeneration in the adult thyroid gland, we observed the regeneration processes of murine thyroid follicles after partial resection of the lower third of the thyroid gland in 10-week-old male C57BL/6 mice. Based on sequential observation of the partially resected thyroid lobe, we found primitive follicles forming in the area corresponding to the central zone of the intact lateral thyroid lobe. The primitive thyroid follicles were multiciliated and had coarsely vacuolated cytoplasm and large vesicular nuclei. Consistently, these primitive follicular cells did not express the differentiation markers paired box gene-8 and thyroid transcription factor-1 (clone SPT24), but were positive for forkhead box protein A2 and leucine-rich repeat-containing G-protein-coupled receptor 4/GPR48. Follicles newly generated from the primitive follicles had clear or vacuolar cytoplasm with dense, darkly stained nuclei. At day 21 after partial thyroidectomy, the tall cuboidal follicular epithelial cells had clear or vacuolar cytoplasm, and the intraluminal colloid displayed pale staining. Smaller activated follicles were found in the central zone of the lateral lobe, whereas larger mature follicles were located in the peripheral zone. Based on these observations, we propose that the follicle regeneration process in the partially resected adult murine thyroid gland associated with the appearance of primitive follicular cells may be a platform for the budding of differentiated follicles in mice.

Abstract P4-06-01: Patient derived DCIS mouse-intraductal (MIND) models recapitulate the full spectrum of human patient pathology and histologic features including progression to invasion in a subset of cases

Abstract Introduction: The 20-year breast cancer mortality rate following a DCIS diagnosis is ∼3%. Radiation and anti-hormonal therapy of DCIS has not resulted in improved overall survival, which argues against the non-selective use of such therapies in DCIS management. However, some DCIS cases do progress to invasive cancer, and these patients may benefit from treatment. A study of 80 DCIS patients followed for up to 30 years reported a 43% progression rate. Notably, progression was not predicted by grade, as 39% of even low-grade DCIS ultimately progressed to invasive cancer. Clearly, there is a need to identify which DCIS lesions are likely to progress. We have developed a novel mouse xenograft model (mouse-intraductal; MIND) to study the molecular basis of DCIS progression and enable identification of suitable biomarkers that predict invasive progression. Methods: MIND involves injection of epithelial cells derived from patient breast lesions into the mammary ducts of immunocompromised mice. Serial sections of mouse mammary glands containing DCIS xenograft lesions were examined at time intervals of 3-14 months post-engraftment by histology using hematoxylin and eosin (H&E) and immunohistochemistry using anti-human cytokeratin 5/19, smooth muscle actin, ER, PR, p53, Ki67 and HER-2. Results: Intraductal injection of cells derived from breast lesions of 28 patients into 133 mice resulted in a successful engraftment rate of 60%. Among these, 12 pure DCIS samples were injected into 35 different mice to create MIND xenografts. As early as three months post-engraftment, the DCIS xenograft cells showed multilayered in situ growth consisting of atypical neoplastic cells with prominent and vesicular nuclei. DCIS MIND xenografts exhibited the full spectrum of human DCIS histologic features, including similar biomarker expression (ER, PR, Ki67, HER-2 and p53) at long-term follow-up after engraftment (up to 12 months). Most remarkably, a subset of xenografts representing 5 patients (5/12; 42%) showed progression to invasion 6-12 months post-engraftment in the absence of any external genetic manipulations. This rate is very similar to that reported for human DCIS progression in untreated patients. MIND DCIS xenograft lesions that progressed showed disruption of basement membrane and myoepithelial layer by the invasive cells, retraction of basement membrane, and micro-invasion. MIND DCIS lesions were enriched in small capillaries, and in some cases clusters of invasive cells appeared inside nearby blood vessels. Conclusion: The MIND xenograft is a viable model for human DCIS progression that recapitulates histologic features of human DCIS, as well as reported rates of progression to invasion. The availability of this innovative model provides a valuable tool for the discovery of new biomarkers to identify DCIS with invasive potential. The identification of high risk DCIS will ultimately help patients and clinicians choose the best course of therapy and avoid the morbidity and costs associated with unnecessary treatment. Citation Format: Behbod F, Limback D, Hong Y, Elsarraj H, Berger J, Heddens E, Valdez K, Smith WP, Inciardi M, Reddick M, Gatewood J, Darrah J, Winblad O, Meierotto R, Ricci L, Wagner J, Amin A, May L, Cusick T, Mammen J, Fields T, Godwin AK, Fabian C, Kaufman C, Tawfik O, Fan F. Patient derived DCIS mouse-intraductal (MIND) models recapitulate the full spectrum of human patient pathology and histologic features including progression to invasion in a subset of cases [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-06-01.

Primary mediastinal clear cell sarcoma: a case report and review of the literature

BackgroundClear cell sarcoma (CCS) is a rare malignant soft-tissue neoplasm that displays melanocytic markers and exhibits striking histopathological features. The tumour has a predilection for the lower extremities and rarely presents in the mediastinum.Case presentationWe present a case of primary mediastinal CCS in a 57-year-old man. Computer tomography (CT) revealed a 12 × 12 × 7.5 cm mass in the anterior mediastinum. Microscopically, the tumour mainly consisted of epithelioid cells with oval vesicular nuclei and eosinophilic cytoplasm. Immunohistochemically, the tumour was positive for human melanoma black 45 (HMB-45) and vimentin but negative for S-100 and Melan-A. Fluorescence in situ hybridisation (FISH) showed a translocation involving the EWSR1 gene region.ConclusionThis report will illustrate that the mediastinum is a potential site for primary CCS and FISH plays an important role in making a conclusive diagnosis.

Primary Neuroendocrine Carcinoma of the Uterine Cervix Treated With Complete Surgical Resection and Adjuvant Combination Chemotherapy

We describe our experience with one case of cervical large cell neuroendocrine carcinoma (LCNC), with an attempt of an adjuvant chemotherapy after complete surgery. The patient was a 66-year-old female (gravida 3, para 2) presenting with genital bleeding. A cervical mass was diagnosed as high-grade neuroendocrine carcinoma. Radical hysterectomy, pelvic lymph node dissection and bilateral salpingo-oophorectomy were performed as primary treatment for the cervical cancer. The surgical specimen of the uterus had an enlarged cervix of 4 cm in diameter with parametrial invasion. Microscopically, the surgical specimen exhibited invasive proliferation of relatively large tumor cells. Peripheral nuclear palisading and central necrosis were also histologically observed. Tumor cells had abundant cytoplasm with vesicular nuclei. The final pathological conclusion was high-grade neuroendocrine carcinoma (LCNC). The postoperative diagnosis was cervical cancer, high-grade neuroendocrine carcinoma (LCNC), pT2bN0M0, FIGO stage IIB, ly (+), v (+). Adjuvant treatment with cisplatin and irinotecan was planned at 4-week intervals. With the completion of three cycles of adjuvant chemotherapy, there was no evidence of recurrent disease. We determined the adjuvant therapy to be effective and well tolerated, and the therapy is now planned to be continued. In conclusion, we experienced a rare case of uterine cervical LCNC. It was surgically resected completely, and adjuvant chemotherapy has been continued. Adjuvant combination chemotherapy with cisplatin and irinotecan is expected to improve the prognosis of cervical LCNC. J Clin Gynecol Obstet. 2017;6(1):23-27 doi: https://doi.org/10.14740/jcgo432w