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Background : Lymphomas are considered uncommon in goats, being the multicentric form with the highest number of cases for the species. Primary intranasal lymphomas are often diagnosed in dogs, cats, and humans. In the literature, there is only a description of a multicentric case involving the frontal sinuses and mucosa of the nasal cavity in a goat; therefore, it is important to describe unusual cases of this disease for the inclusion of new clinical and pathological characteristics in the ruminant clinic medicine. The objective of this work is to describe a case of T-cell lymphoma in the nasal cavity of a young goat. Case : The animal had dyspnea and respiratory noise for 15 days. Clinical examination showed nodulation in the right nasal cavity associated with serosanguinous secretion. Tracheostomy was performed; however, after 30 days the animal was euthanized. A sagittal plane of the head showed a pinkish-gray mass in the right and left nasal cavity, with a smooth, multilobulated surface, smooth adhering to the rostral portion of the dorsal concha and occluding the dorsal nasal meatus. Submandibular lymph nodes were slightly enlarged. Histopathological examination of the nasal cavity revealed a non-encapsulated, poorly delimited and ulcerated tumor composed of round cells arranged in a mantle supported by a discrete fibrovascular stroma extending the mucosa and lamina propria. Cells were round with sparse, eosinophilic and poorly delimited cytoplasm. Nuclei varied from round to elongated with condensed chromatin and evident nucleoli. Occasionally, aberrant nuclei, reniform shape and multinucleated cells were seen. Pleomorphism was moderate characterized by anisocytosis and anisocariosis. Typical and atypical mitosis were frequent (0-4 per field of highest magnification [400x]). Amidst the neoplasm, there were multifocal areas of necrosis and hemorrhage associated with a mild lymphocytic inflammatory infiltrate. Immunohistochemistry showed positive immunostaining for Vimentin antibodies and CD3, and negative for pan CK and CD20. Discussion : The lymphomas immunophenotyping is little used when it comes to farm animals, and there are few studies that use this technique for the definitive diagnosis of these neoplasms for small ruminants. The use of this technique must be considered in each case, in order to determine the pathogenesis, the accurate diagnosis and the origin of the neoplastic lymphocytes. In goats, T-cell lymphomas are the most diagnosed, although cases of multicentric B-cell lymphomas with ocular involvement have been diagnosed. In view of the clinical picture of the case described, infectious rhinitis already described in goats, such as aspergillosis and protothecosis, should be included as differential diagnoses. However, the anatomopathological findings facilitate the direction of the diagnosis, since infectious rhinitis presents as nodules / ulcerated masses or focal areas of necrosis associated with purulent secretion and in the histopathological examination it is possible to observe the intralesional etiological agents. In addition, the enzootic ethmoidal tumor must be included, as it has similar clinical signs and affects young animals, but they are adenomas/adenocarcinomas that affect the ethmoidal nasal shells induced by a retrovirus. Lymphomas in the caprine species are rare in the Northeastern semi-arid, but that in the present diagnostic routine occasionally occurs, being important the first description of its nasal shape for its inclusion in the differential diagnoses of diseases that present with clinical obstruction and dyspnea for the species. Keywords: hematopoietic neoplasia, immunophenotyping, lymphocytes, dyspnea. Descritores: neoplasia hematopoietica, imunofenotipagem, linfocitos, dispneia. Titulo: Linfoma de celulas T na cavidade nasal de caprino.

Cutaneous syncytial myoepithelioma (CSM) is a recently recognized variant of myoepithelial neoplasms. CSM is characterized by an intradermal syncytial proliferation of spindled, ovoid, and histiocytoid cells. Immunohistochemically, tumor cells usually show strong positivity for S-100 and EMA. Here, we report a case of CSM in the thigh of a 51-year-old Japanese woman. Histopathological findings showed a sheet-like growth of ovoid cells and histiocytoid cells with an eosinophilic syncytial cytoplasm, and adipocytic metaplasia was widely observed in the tumor. Immunohistochemical staining revealed a diffuse strong pattern for EMA, smooth muscle actin (SMA), and HHF35 and variable positivity for S-100 protein and p63 in ovoid and histiocytoid cells without significant mitotic figures or pleomorphism. In addition, EWSR1-PBX3 gene fusion, which is characteristic of CSM, was observed in the tumor. Based on these findings, we diagnosed the patient as having CSM. Our case suggests that CSM could show extensive adipocytic metaplasia, which could make its histopathological diagnosis challenging. This article is protected by copyright. All rights reserved.

The World Health Organization endorses molecular subclassification of endometrial endometrioid carcinomas (EECs). Our objectives were to test the sensitivity of tumor morphology in capturing p53 abnormal (p53abn) cases and to model the impact of p53abn on changes to ESGO/ESTRO/ESP (European Society of Gynaecological Oncology/European Society for Radiotherapy and Oncology/European Society of Pathology) risk stratification. A total of 292 consecutive endometrial carcinoma resections received at Foothills Medical Centre, Calgary, Canada (2019–2021) were retrieved and assigned to ESGO risk groups with and without p53 status. Three pathologists reviewed the representative H&E‐stained slides, predicted the p53 status, and indicated whether p53 immunohistochemistry (IHC) would be ordered. Population‐based survival for endometrial carcinomas diagnosed during 2008–2016 in Alberta was obtained from the Alberta Cancer Registry. The cohort consisted mostly of grade 1/2 endometrioid carcinomas (EEC1/2; N = 218, 74.6%). One hundred and fifty‐two EEC1/2 (52.1% overall) were stage IA and 147 (50.3%) were low risk by ESGO. The overall prevalence of p53abn and subclonal p53 was 14.5 and 8.3%, respectively. The average sensitivity of predicting p53abn among observers was 83.6%. Observers requested p53 IHC for 39.4% with 98.5% sensitivity to detect p53abn (99.6% negative predictive value). Nuclear features including smudged chromatin, pleomorphism, atypical mitoses, and tumor giant cells accurately predicted p53abn. In 7/292 (2.4%), p53abn upgraded ESGO risk groups (2 to intermediate risk, 5 to high risk). EEC1/2/stage IA patients had an excellent disease‐specific 5‐year survival of 98.5%. Pathologists can select cases for p53 testing with high sensitivity and low risk of false negativity. Molecular characterization of endometrial carcinomas has great potential to refine ESGO risk classification for a small subset but offers little value for approximately half of endometrial carcinomas, namely, EEC1/2/stage IA cases.

OBJECTIVES: To evaluate the ocular surface, meibomian glands and corneal structural changes using in vivo confocal microscopy (IVCM) in patients receiving aromatase inhibitor (AI) therapy due to the breast cancer. METHODS: This prospective observational study included 13 patients undergoing AI therapy. The patients were evaluated before the treatment, at 3- and 6-month timepoints of AI therapy. To examine the ocular surface and tear film, corneal sensitivity (CS) measurement with Cochet–Bonnet Aesthesiometer, tear film break-up time (TBUT), lissamine green (LG) staining, Schirmer I test with anaesthesia (ST) and the ocular-surface disease index (OSDI) questionnaire were performed consecutively. Corneal cell densities and sub-basal nerve plexus were evaluated with IVCM (ConfoScan 4, Nidek, Japan). Finally, quantitative MG drop-out assessment was made using infrared meibography. Shapiro Wilk, Friedman’s and Post-hoc Dunn tests were used for the statistical analysis. RESULTS: TBUT, ST scores, basal epithelium, anterior and posterior keratocytes and endothelial cell densities, long and total sub-basal nerve densities were found to be decreased (p

Clear cell ("hemangioblastoma-like”) stromal tumor of the lung (CCST-L) is a recently described distinctive rare pulmonary neoplasm of unknown histogenesis and molecular pathogenesis. Only seven cases have been reported in two recent studies, although additional cases might have been reported under the heading of extra-neural pulmonary hemangioblastoma. We herein describe 4 CCST-L cases, 3 of them harboring a YAP1-TFE3 fusion. The fusion-positive tumors occurred in 3 females, aged 29, 56 and 69 years. All presented with solitary lung nodules measuring 2.3 to 9.5 cm. Histologically, all tumors showed similar features being composed of relatively uniform medium-sized epithelioid to ovoid cells with clear cytoplasm and small round monomorphic nuclei. Scattered larger cells with enlarged hyperchromatic nuclei and marked pleomorphism were noted in two cases. The tumors were associated with a hypervascularized stroma with variable but essentially subtle resemblance to capillary hemangioblastoma and perivascular epithelioid cell tumor (PEComa). Immunohistochemistry was negative for all lineage-specific markers. Targeted RNA sequencing revealed a YAP1-TFE3 fusion in 3 of 4 cases. All three tumors revealed homogeneous nuclear TFE3 immunoreactivity. Two patients were disease-free at 36 and 12 month. The third patient had biopsy-proven synchronous renal and hepatic metastases, but extended follow-up is not available (recent case). The 4(th) case lacking the fusion affected a 66-year-old female and showed subtle histological differences from the fusion-positive cases, but had comparable TFE3 immunoreactivity. CCST-L represents a distinctive entity unrelated to hemangioblastoma and likely driven by recurrent YAP1-TFE3 fusions in most cases. The relationship of our cases to the recently reported “hemangioblastoma-like” CCST-L remains to be determined. Analysis of larger series is paramount to delineate the morphologic spectrum and biologic behaviour of this poorly characterized entity.

Granulosa cell tumour, an ovarian neoplasm of stromal origin, is an important tumour related to oestrogenic dominance syndrome and cystic endometrial hyperplasia-pyometra complex. In order to analyse ovarian tumour´s malignant potential, immunohistochemical markers can be used, such as anti-HER2 and anti-Ki-67. The aim of this study was to evaluate the expression of immunohistochemical markers HER-2 and Ki-67 in granulosa cell tumour from bitches´ ovaries. In HER-2 immunomarker analysis using the HercepTest® method, most tumours were classified as 2+ (moderate labelling). Concerning Ki-67 immunomarker, only one case was described as having a high proliferative index. An association was found between immunostained cell percentage by anti-HER-2 antibodies and high pleomorphism, represented by the pattern of follicular/trabecular tumour arrangement. There was no correlation between anti-Ki-67 and anti-HER-2 antibody immunostaining intensities, probably due to only one case with a high Ki-67 index. With an effective protocol for HER-2 and Ki-67 immunohistochemical identification in granulosa cell tumours in bitches, it was possible to characterize this neoplasm proliferation profile.

Histologic distinction between melanoma ex-blue nevus and cellular blue nevus (CBN) can often be difficult, but features supporting melanoma include infiltrative growth pattern, frequent mitoses, cytologic atypia and pleomorphism, cell crowding, and tumor necrosis. Unfortunately, these features are not constantly dependable and frequently borderline lesions exist, so-called atypical CBN, which lack explicit malignant features. Furthermore, some CBN and atypical CBN show an assortment of features, which may lead to their misdiagnosis as melanoma, but to date necrosis is generally absent. We present an unusual case of an atypical cellular blue nevus with extensive necrosis mimicking melanoma ex-blue nevus.

Salivary gland tumors are neoplasms characterized by a high level of pleomorphism and histological overlap. One tumor may contain several cell types; therefore, it is necessary to include immunohistochemical staining, as well as morphometric analysis of tumor cells as prerequisites for an appropriate diagnosis. Our research included 120 tumors, such as pleomorphic adenoma, Warthin tumor, basal cell adenoma, myoepithelioma, adenoid cystic carcinoma, mucoepidermoid carcinoma, salivary duct carcinoma, polymorphous low-grade carcinoma and myoepithelial carcinoma. The aim of the study was to differentiate benign and malignant tumors based on the characteristics of nuclei. The expression of Ki67 and the morphometric nuclear parameters ? area, perimeter, Feret diameter, integrated optical density, circularity, and roundness, were analyzed. It was observed that the Ki67 proliferative index was statistically significantly higher in malignant tumors (P

AIM The evaluation of the prognostic role of nuclear pseudoinclusions (NPIs) and nuclear grooves (NGs) in UM. PATIENTS AND METHODS We examined the presence of NPIs and NGs in hematoxylin and eosin-stained tissue sections from 164 removed eyeballs with uveal melanoma (UM) and analyzed statistical relationships with clinical and pathological parameters and the long-term survival rate. RESULTS We observed NPIs in 38% and NG in 21% of all UM. The presence of NPIs was significantly positively correlated with epithelioid type, marked pleomorphism, and the presence of multinucleated giant cells, macro-nucleoli and multiple nucleoli. Patients with UM with NPIs had a significantly reduced overall survival rate (p

Epithelial-myoepithelial carcinoma (EMC) is a rare, low-grade, malignant salivary neoplasm. Establishing an accurate cytological diagnosis is often challenging owing to its rarity, bland cytologic appearance and variable representation of cell populations in the smears. The diagnostic struggle is more so when the aspiration is from a metastatic site with an unknown primary, as in such cases the list of differential diagnoses expands further. A 58-year-old female presented with a low-back pain from last one month. On examination, she also had a level III, right cervical swelling for the last 20 years. Radiology revealed a lytic lesion in the left acetabulum. She had undergone surgery 35 years ago for a right-sided upper neck swelling, the medical records of which were not available. Fine needle aspiration (FNA) from the cervical swelling was performed. The smears were cellular and showed predominantly dispersed, round to polygonal tumor cells with mild pleomorphism, eccentric nuclei, coarse chromatin, occasional nucleoli and moderate cytoplasm with some showing vacuolations. The cell-block section revealed tumor cells arranged in the form of tubules lined by dual layer of tumor cells without any chondromyxoid stroma. On immunocytochemistry, the luminal cells showed positivity for CK7 (epithelial marker) and the abluminal cells showed positivity for p63 (myoepithelial marker). Based on these features, a final diagnosis of metastatic epithelial-myoepithelial carcinoma was rendered. The present report highlights the characteristic cytomorphological and immunocytochemical features of EMC and reiterates the diagnostic accuracy of FNAC for diagnosis of such challenging cases.

Introduction: Desmoplastic fibroma is an extremely rare, locally aggressive, benign bone tumour with incidence of 0.1% of primary bone tumors. It is composed of spindle cells with minimal cytological atypia and abundant collagen. Diagnosis is made on radiology and histopathology. Case Summary: A 17yr female patient presented with pain and swelling in left forearm since 9yrs, slowly progressive in nature. Radiograph showed an osteolytic lesion of the proximal ulna. En-bloc excision was done. Grossly the tumor was 13x6x2.5cm, hard in consistency with grey-white mass on cut section. Microscopically it was composed of spindle shaped cells with elongated bland appearing nuclei arranged in whorled pattern and fascicles with abundant collagen present between spindle cells. No pleomorphism or mitoses were noted. Conclusion: Desmpoplastic fibroma is a very rare locally aggressive benign neoplasm of bone. The diagnosis and management are often difficult and requires a combined speciality approach. Keywords: Desmoplastic fibroma, Ulna, Bone tumor, Spindel cell, Collagen.

Several molecular subtypes of bladder cancer were identified with differing clinical behavior and responses to platinum-based chemotherapy. But so far, their urothelial histomorphologic features, besides association with some variant histologies, have remained fully undefined. We sought to characterize the histological features of genomically classified bladder cancers more extensively to tumor in radical cystectomy (RC) specimens. Forty-eight bladder cancers submitted to The Cancer Genome Atlas (TCGA) were classified using the BASE47 genomic classifier into luminal subtype (LS) (14 cases), basal subtype (BS) (18 cases), and claudin-low subtype (CLS) (16 cases), and TCGA samples and the corresponding RC specimens were histologically assessed. Marked pleomorphism was more extensive in CLS tumors (87.5% had15% extent) than in LS tumors (21.4%) (p = 0.0006), whereas the extent in BS tumors was in between LS and CLS tumors. Pleomorphism in distant carcinoma in situ appeared to correlate with that in the main tumor. Ki-67 proliferation was higher in CLS tumors (mean = 61%) than in LS tumors (mean = 29%) or BS (mean = 30%) (p 0.001). Squamous differentiation was more extensive in BS and CLS tumors (38.2% of BS and CLS tumors versus 7.1% of LS tumors had30% squamous, p = 0.040). Sarcomatoid change was present in BS and CLS tumors only. The micropapillary variant was identified in LS (3/14) and BS (4/18) tumors only. Histologic features associated with aggressiveness (eg, marked pleomorphism, high proliferation, and sarcomatoid change) are enriched in CLS tumors, correlating with its known poorer outcome that may provide hints in their microscopic distinction. Features more associated with BS than with LS tumors (eg, squamous, marked pleomorphism, and sarcomatoid change) are also identified or enhanced in CLS tumors, supporting the genomic findings suggesting CLS tumor as a hyperbasal form of BS tumor.

Feline injection site sarcomas (FISS) are aggressive, with high recurrence and rarely metastasising. The objective of this study was to evaluate, by immunohistochemistry, the expression of oestrogen (ER) and progesterone (PR) receptors in FISS and correlate them with clinical and histopathological aspects. This was a retrospective study with 51 cases of FISS. Immunohistochemistry was performed to detect vimentin, ER, PR and Ki67 expression. Clinical, histopathological and immunohistochemical characteristics were predictor variables and the expression of ER and PR were the dependent ones. Twenty-eight (55%) of the 51 FISS cases were female and 23 (45%) male with 10.7 ± 4.2 years and median tumour size of 3 cm (2.0-5.4). The trunk was the most affected site, with 38 cases (84%). Histological grade III was observed in 57% of the cases, considering differentiation score, necrosis and mitotic index. ER expression, positive in 64% of cases, was associated with the mitotic index (P = .05) and degree of pleomorphism (P = .04). PR was not associated with the variables and 63% of cases were negative for this receptor. Thus, ER expression can affect tumour growth. The knowledge on the FISS hormonal expression is important to clarify the pathophysiological mechanisms. Further studies are needed to predict the value of ER expression in the prognosis of FISS.

Herein we describe a rare case of systemic Listeria monocytogenes infection with concurrent pleural mesothelioma in a stray cat that was found dead and submitted for autopsy. Gross pathology changes consisted of thoracic clear yellow fluid admixed with suspended fibrin strands; clear-to-tan, variably sized

Supplemental digital content is available in the text., Objective The aim of the study was to describe the demographic, clinical, and histopathologic features of differentiated vulvar intraepithelial neoplasia (dVIN) and vulvar aberrant maturation (VAM). Methods Specimens from 2010 to 2020 reported as dVIN or VAM were reviewed. Clinical data included age, rurality, symptoms, and evidence of lichen sclerosus (LS). Histopathologic data included epithelial thickness, keratinization, architectural and dyskeratotic features, stroma, p16, and p53. Differentiated vulvar intraepithelial neoplasia and VAM were distinguished by assessment of basal nuclear chromatin, enlargement, pleomorphism, and mitoses. Results One hundred twenty women with a median age of 71 years had 179 examples of dVIN and VAM. Squamous cell carcinoma was concurrent in 66% and associated with rurality. Ten percent were asymptomatic, and all but 3 had evidence of LS. Differentiated vulvar intraepithelial neoplasia showed a range of thickness, architecture, and dyskeratosis; its unifying !feature was basal atypia. Differentiated vulvar intraepithelial neoplasia displayed hyperchromasia in 83% and easily observed mitoses in 70%. Nonkeratinizing morphology, subcategorized into basaloid and intermediate, occurred in 24% of women with dVIN. Traditional dVIN represented 62% of keratinizing cases; the remainder were atrophic (13%), hypertrophic (13%), acantholytic (8%), or subtle (5%). Vulvar aberrant maturation had abnormal stratum corneum, acanthosis, premature maturation, and enlarged vesicular nuclei. Null p53 helped distinguish dVIN from VAM and dermatoses. Conclusions The morphology of dVIN encompasses nonkeratinizing and keratinizing types, the latter subdivided into traditional, acantholytic, atrophic, hypertrophic, and subtle. Diagnosis relies on basal atypia with supportive p16 and p53. Atypia exists on a biologic spectrum with mild abnormalities of VAM and reactive change. Identification of dVIN and VAM requires collaboration between clinicians and pathologists experienced in vulvar disorders.

Breast fibroepithelial lesions (FELs) encompass the common fibroadenoma (FA) and relatively rare phyllodes tumour (PT); the latter entity is usually classified as benign, borderline or malignant. Intratumoural heterogeneity is frequently present in these tumours, making accurate histologic evaluation challenging. Despite their rarity, PTs are an important clinical problem due to their propensity for recurrence and, in the case of malignant PT, metastasis. Surgical excision is the mainstay of management. Recent work has uncovered myriad genetic alterations in breast FELs. In this study, exome sequencing was performed on seven cases of morphologically heterogeneous breast FELs, including FAs, PTs of all grades, and a case of metaplastic spindle cell carcinoma arising in PT, in order to elucidate their intratumoural genetic repertoire. Gene mutations identified encompassed cell signalling, tumour suppressor, DNA repair and cell cycle regulating pathways. Mutations common to multiple tumour regions generally showed higher variant allele frequency. Frequent mutations included MED12, TP53, RARA and PIK3CA. Histological observations of increased cellular density and pleomorphism correlated with mutational burden. Phylogenetic analyses revealed disparate pathways of possible tumour progression. In summary, histological heterogeneity correlated with genetic changes in breast FELs.

Background Clear‐cell chondrosarcomas (CCCSs) constitute a very rare subtype of chondrosarcoma. CCCS may radiologically mimic chondroblastoma, and given the difference in surgical approach, it is important to distinguish these two entities preoperatively. Design Using the institutional digital records, we identified histologically verified CCCS between 1996 and 2013, where preoperative fine‐needle aspiration (FNA) cytology was available. Clinical characteristics were categorized and described, and FNAs were reviewed by a panel of senior cytopathologists. In addition, corresponding radiological imaging was reviewed by senior radiologists, and a literature review on CCCS and chondroblastoma was conducted. Results A total of seven CCCS FNAs were identified from six patients. The cytomorphology showed low to intermediate cellular smears of clusters and single round or oval tumor cells. Tumor cells had rounded (sometimes binucleated) nuclei with limited pleomorphism and rich vacuolated cytoplasm. Chondroid background matrix was always found. While CCCS patients had a significantly higher age at diagnosis compared to chondroblastoma, no age cut‐off would distinctly separate the two. Conclusions CCCS has distinguished cytomorphological features on FNA smears. CCCS should be considered as a possible differential diagnosis in adults (>25 years) with a radiological suspicion of chondroblastoma. Since radiology and patient age cannot conclusively distinguish CCCS from chondroblastoma, FNA may prove an important tool for correct preoperative diagnosis of CCCS.

Aims The aims of this study were to review the histological features useful for the identification of metastases to the breast and to investigate the impression that this diagnosis has become more common. Methods and results The histological features of metastases to the breast from 2008 to 2018 were reviewed. Seventy-four biopsies from 66 patients were identified: 1% compared with primary carcinoma of the breast. Non-haematological metastases comprised 0.75% compared with 0.3% in a series from 1996 to 2005. The most common tumour types were pulmonary carcinoma (22), lymphoma (15), melanoma (13), gastrointestinal carcinoma (eight) and serous papillary carcinoma (four). In 73% there were histological features that were not typical of primary mammary carcinoma. Some metastases were histologically similar to breast cancer and the history was essential to making the correct diagnosis. Useful histological clues included small-cell morphology for pulmonary carcinoma, glands containing necrosis for gastrointestinal carcinoma, intranuclear inclusions, marked pleomorphism and spindle cells for melanoma, clear cells for renal carcinoma, papillary architecture for serous papillary carcinoma and sheets of centroblasts or nodules of centroblasts and centrocytes for lymphoma. Useful immunohistochemical markers included TTF-1 for pulmonary carcinoma, S100, melan-A and HMB45 for melanoma, CK20 and CDX2 for colorectal carcinoma, PAX8 and WT1 for serous papillary carcinoma and lymphoid markers for lymphomas, in addition to the absence of expression of mammary markers ER, GATA3 and GCDFP-15. Conclusion The majority of metastases to the breast have histological clues to the diagnosis. Immunohistochemistry is helpful. This diagnosis is being made more frequently.

Cadmium is a toxic, heavy industrial metal that causes serious environmental health hazards. Cadmium containing compounds have been classified as known human carcinogens and epidemiological data show causal associations to different types of cancers. This study designed to assess the carcinogenic effects of Cadmium on the gingival tissue of rats. Material and methods; Sixteen male albino Rats (age: 8 to 10 weeks and about 150 to 180 g body weight) from Animal Center of Faculty of Medicine, Mansoura University. The animals were divided into two equal groups, group I (control) and group II (cadmium chloride) rats were given 2 ml dose of a solution containing 10 mg/kg body weight of monohydrated cadmium chloride orally by gavage needle for 24 days. By the end of experiments, gingival epithelium around the teeth were carefully dissected, processed and stained using Haematoxyline & Eosin and immunohistochemical evaluation by iNOS. Statistical analysis was done to observe the statistical significant differences between the Cd group and control group in relation to dysplastic changes and iNOS immunoreaction. Results: the gingival tissue of Cd group revealed several dysplastic changes as, drop shape rete pegs, loss of polarity of basal cells, nuclear hyperchromatism, pleomorphism and increased mitotic pattern. a statistical significant difference regarding iNOS immunoreaction was found between control group and Cd group. conclusion to this study Cadmium chloride at low concentration and longtime of exposure can cause dysplastic changes in gingival tissue of rats.

Aims Solitary fibrous tumours (SFTs) are rare mesenchymal neoplasms with recurrence rates of 10-30%. Current risk stratification systems for extrameningeal SFTs are based on cohorts with limited follow-up and are not suitable for prediction of late recurrences. In this study we aimed to develop a prognostic model accounting for both early and late recurrences using a relatively large patient cohort with long-term follow-up. Methods and results Clinicopathological factors were analysed in a cohort of 100 extrameningeal, STAT6-positive SFTs. Median follow-up for overall survival (OS) and recurrence-free interval (RFi) were 121 and 84 months, respectively. Disease relapse occurred in 31% of patients and median time to recurrence was 63 months. In univariate analysis mitotic count, necrosis, male gender and presence of severe atypia and pleomorphism were associated with inferior RFi. Mitotic count, necrosis and male gender were independent predictors of recurrence in multivariate analysis. Previously published risk models were also statistically associated with RFi in our cohort, but failed to reliably identify low-risk patients due to poor prediction of late recurrences. A novel risk score based on mitotic count, necrosis and gender was able to stratify patients into low-, intermediate- and high-risk groups for both early and late recurrences. Conclusions In this cohort of patients with extrameningeal SFT and long-term follow-up mitotic count, necrosis and gender were independent prognostic markers of recurrence. We propose a novel risk score based on these factors and accounting for late recurrences, which should be validated in external cohorts with sufficient follow-up time.

Astroglial complexity and pleomorphism have increased significantly with hominid evolution. This suggests a potential association between glial evolution and the development of human cognition, as well as between glial evolution and the advent of human-selective neurodegenerative and neuropsychiatric disorders.

Germinotropic lymphoproliferative disorder (GLPD) is a poorly characterized lymphoproliferative entity, recently included in the World Health Organization classification of hematolymphoid neoplasms. The histological pattern of this disease comprises monotypic plasmablasts that involve the germinal centers of the lymphoid follicles (germinotrophism), forming confluent aggregates positive for both human herpes virus type 8 (HHV8) and Epstein-Barr virus. Currently, after 17 years of its first description, only 18 cases have been reported. In this article, we describe a case of a GLPD presenting in an immunocompetent 79-year-old woman with localized axillary lymphadenopathy, showing a prominent sinusoidal growth pattern, with no evidence of germinotrophism or extrasinusoidal spread. Stinking pleomorphism in tumor cells was also noted. An extension study has not revealed involvement of other groups of lymph nodes or extralymphoid sites. The patient is alive and has shown no relapse after 8 years follow-up (the longest follow-up reported period for this entity). This previously unrecognized pure sinusoidal growth pattern along with the striking pleomorphism in neoplastic cells closely mimics the appearance of an anaplastic large cell lymphoma. GLPD is not usually considered in such a setting, but it should be included in the differential diagnosis of sinusoidal proliferations. Our findings contribute to the expansion of the morphological spectrum of HHV8-associated lymphoproliferative lesions and aids in the characterization of the very infrequent GLPD entity.

Background Primary ovarian mucinous tumors with mural nodules are very rare. The histogenesis of the mural nodules remains unclear. Methods We investigated the clincopathological and molecular features in 3 cases with mural nodules. Results Patient 1 was diagnosed as mucinous carcinoma with mural nodules of anaplastic carcinoma that was composed of CK+ and CK7+ spindled cells and polygonal cells with marked pleomorphism. Aberrant p53 staining was found in the mural nodules rather than in the mucinous components. A concordant KRAS mutation (c.35G > A p.G12A) was identified in both mucinous tumors and mural nodules. She died of disease at 44 months. The mural nodule in patient 2 was interpreted as a sarcoma, no other specified. The uniform short spindle cells were separated by abundant myxoid matrix. They were CD10 + , CCND1-, SMA-, and negative for break-apart BCOR, PHF1, and JAZF1 FISH assay. The adenocarcinomatous component harbored LOH at D18S51 and FGA loci while the sarcomatous component had LOH at D19S433. She had lung metastasis at 18 months and was alive without evidence of disease for 40 months. Patient 3 harbored multiple mural nodules that were composed of vimentin+, focal CK+, atypical spindle cells. A diagnosis of sarcoma-like mural nodules was rendered. She was alive with no evidence of disease for 13 months. No hotspot mutant AKT1, KRAS, HRAS, and PI3KCA alleles were found in patients 2 and 3. Conclusions Mural nodules with anaplastic carcinoma or with true sarcomas may represent the dedifferentiation form of mucinous tumors or collision tumors, respectively. The worrisome histology in sarcoma-like mural nodules necessitates meticulous treatment for these patients.

ALK-fused spitzoid neoplasms represent a distinctive group of melanocytic lesions. To date, few studies addressed genetic and chromosomal alterations in these lesions beyond the ALK rearrangements. Our objective was to study genetic alterations, including ALK gene fusions, telomerase reverse transcriptase promoter (TERT-p) mutations, chromosomal copy number changes, and mutations in other genes. We investigated 29 cases of Spitz lesions (11 Spitz nevi and 18 atypical Spitz tumors), all of which were ALK immunopositive. There were 16 female and 13 male patients, with age ranging from 1 to 43 years (mean, 18.4 years). The most common location was the lower extremity. Microscopically, all neoplasms were polypoid or dome shaped with a plexiform, predominantly dermally located proliferation of fusiform to spindled melanocytes with mild to moderate pleomorphism. The break-apart test for ALK was positive in 17 of 19 studied cases. ALK fusions were detected in 23 of 26 analyzable cases by Archer FusionPlex Solid Tumor Kit. In addition to the previously described rearrangements, 3 novel fusions, namely, KANK1-ALK, MYO5A-ALK, and EEF2-ALK, were found. Fluorescence in situ hybridization for copy number changes yielded one case with the loss of RREB1 among 21 studied cases. TERT-p hotspot mutation was found in 1 of 23 lesions. The mutation analysis of 271 cancer-related genes using Human Comprehensive Cancer Panel was performed in 4 cases and identified in each case mutations in several genes with unknown significance, except for a pathogenic variant in the BLM gene. Our study confirms that most ALK fusion spitzoid neoplasms can be classified as atypical Spitz tumors, which occurs in young patients with acral predilection and extends the spectrum of ALK fusions in spitzoid lesions, including 3 hitherto unreported fusions. TERT-p mutations and chromosomal copy number changes involving 6p25 (RRB1), 11q13 (CCND1), 6p23 (MYB), 9p21 (CDKN2A), and 8q24 (MYC) are rare in these lesions. The significance of mutation in other genes remains unknown.

Background The cytologic diagnosis of poorly differentiated thyroid carcinoma (PDTC) is difficult because it lacks salient cytologic findings and shares cytologic features with more commonly encountered neoplasms. Due to diverse cytologic findings and paucicellularity of PDTC, standardization of cytologic diagnostic criteria is limited. The purpose of this study is to investigate and recognize diverse thyroid findings of fine needle aspiration (FNA) cytology and frozen smear cytology in diagnosis of this rare but aggressive carcinoma. Methods The present study included six cases of FNA cytology and frozen smears of histologically diagnosed PDTCs. Results PDTC showed cytologic overlap with well-differentiated thyroid carcinomas (WDTCs). Five of six cases showed dedifferentiation arising from well differentiated thyroid carcinomas. Only one de novo PDTC showed highly cellular smears composed of discohesive small cells, high nuclear/cytoplasmic (N/C) ratio, prominent micronucleoli, and irregular nuclei. Retrospectively reviewed, these findings are highly suspicious for PDTC. Cytologic findings of nuclear atypia, pleomorphism, and irregularity were frequently found, whereas scattered small cells were seen only in the de novo case. Conclusions Heterogeneous cytologic findings of PDTCs are shared with those of WDTCs and contribute to difficult preoperative cytologic diagnoses. Most PDTCs show dedifferentiation from WDTCs. Albeit rare, de novo PDTC should be considered with cytology showing discohesive small cells with high N/C ratio. This will enable precise diagnosis and prompt treatment of this aggressive malignancy.

As cancer care is transitioning to personalized therapies with necessary complementary or companion biomarkers there is significant interest in determining to what extent non-invasive liquid biopsies reflect the gold standard solid biopsy. We have established an approach for measuring patient-specific circulating and solid cell concordance by introducing tumor touch preparations to the High-Definition Single Cell Analysis workflow for high-resolution cytomorphometric characterization of metastatic colorectal cancer (mCRC). Subgroups of cells based on size, shape and protein expression were identified in both liquid and solid biopsies, which overall displayed high inter- and intra- patient pleomorphism at the single-cell level of analysis. Concordance of liquid and solid biopsies was patient-dependent and between 0.1-0.9. Morphometric variables displayed particularly high correlation, suggesting that circulating cells do not represent distinct subpopulations from the solid tumor. This was further substantiated by significant decrease in concentration of circulating cells after mCRC resection. Combined with the association of circulating cells with tumor burden and necrosis of hepatic lesions, our overall findings demonstrate that liquid biopsy cells can be informative biomarkers in the mCRC setting. Patient-specific level of concordance can readily be measured to establish the utility of circulating cells as biomarkers and define biosignatures for liquid biopsy assays.

Introduction: Mesenchymal tumours of gastrointestinal tract are a heterogenous group of nonepithelial tumours of variable mesenchymal cell histogenesis. Gastrointestinal stromal tumour (GIST) is the most common primary mesenchymal tumour of the gastrointestinal tract and spans a clinical spectrum from benign to malignant. This study evaluated the clinicopathological morphological and immunohistochemical features of GIST of the intestinal tract. Materials and Methods: All evaluable cases of mesenchymal tumors of the gastrointestinal tract were studied from January 2007 to December 2012. Tissue microarray was constructed and Immunohistochemical expression of CD 117, CD 34, DOG1, SMA, S100, Ki 67 were studied. Results: Gastrointestinal stromal tumours were the most common mesenchymal tumours of the gastrointestinal tract accounting to 77.96%. The median age of presentation was 51 years with near equal sex preliction with early clinical presentation. The gastric tumours were of significantly bigger size with increased expression of CD 34. Majority of tumors were of bigger size (>10 cm, 47%) thereby increased number of tumours in high risk category (76%). Spindle cell pattern was the most common morphology (69.5%). Epitheliod histology was significantly associated with pleomorphism and atypia (p value – 0.029). Inclusion of anatomic site into the risk category will help in better stratificaion. High risk tumours showed significant areas of necrosis when compared with low risk tumours (p value- 0.0156). Tumours of older age group (>40 years) showed significant mitotic activity (p value 0.04). DOG1 is a very sensitive (97.8%) marker for GIST. A wide immunopanel with emphasis on DOG 1 positivity for precise diagnosis of GIST and classification of mes enchymal tumors of the GI tract. Keywords: DOG 1, Mesenchymal tumours, Gastrointestinal stromal tumour, Clinicopathological, Immunohistochemical features.

Purpose: Orbital Solitary Fibrous Tumor (SFT) is a rare spindle cell neoplasm of mesenchymal origin.1 We describe the clinical presentation, radiological features, pathological features of a 23yr old female patient with orbital malignant SFT. Observation: We report a case of Malignant Orbital Solitary Fibrous Tumor of the orbit in a 23yr old female who presented with painless unilateral proptosis of the left globe noticed by her in the last 1 month. Computed Tomography scan showed a well-defined homogeneous enhancing soft tissue density in superior and extraconal compartment, with no evidence of bony erosion or calcification. Enbloc tumor resection confirmed SFT based on histopathological and immunohistochemistry studies. Microscopic examination showed a highly cellular tumor, moderate amount of pleomorphism and increased mitosis (>4/10). Immunohistochemistry studies confirmed diagnosis as tumor was diffuse positivity with CD34, BcL2 positive, STAT6 positive with ki 67 high i.e. a 9-10% proliferative index in hot spot areas. Desmin, CD99, S100 and EMA was negative. Patient subsequently was also given External Beam Radiotherapy. Conclusion: Solitary Fibrous Tumors are rare tumor, which should be included in differential diagnosis of soft tissue tumor of the orbit. Combination of Computed Tomography scan, histological examination and immunohistochemical markers provide an accurate diagnosis. Complete surgical resection along with long term follow up is essential. Keywords: Solitary fibrous tumor (SFT), Proptosis, Tumor.

Myositis ossificans (MO) is an uncommon myofibroblastic proliferation that may closely mimic sarcoma. A 33-year old woman presented with a 2-cm breast mass. A core needle biopsy showed highly cellular spindle cell proliferations with atypia and high proliferation activity. Focal areas of immature osteoid-like matrix were seen. After immunohistochemical analysis, a diagnosis of metaplastic breast cancer was made. Because of the proximity of the tumor to the rib, resection of the tumor including partial resection of the rib was carried out. Complete examination of the excised lesion allowed the correct diagnosis of MO. Only the resection specimens contained a predominance of mature organoid bone tissue admixed with variably cellular myofibroblastic proliferations with the typical zonal pattern, characteristic of MO. The diagnosis of MO was not possible on the initially performed core needle biopsy because biopsy material reflected only the central proliferative portion of the lesion showing increased pleomorphism and early osteoid formation. This case highlights the pitfall related to this unusual presentation of a benign lesion and points to the necessity to include MO in the differential diagnosis of triple-negative metaplastic breast cancer.

Bowenoid papulosis (BPap) is an uncommon skin disorder linked to human papillomavirus (HPV) infection and characterized clinically by the presence of scattered papules or small plaques, multiple and pigmented, that involve the stratified squamous epithelium. Bowen disease (BD) is recognized as the main differential diagnosis of BPap. An 80-year old white woman was referred for the evaluation of multiple, brown verrucous papules measuring 3 to 4 mm in diameter on the right maxillary gingiva. Histopathological analysis revealed disturbed epithelial maturation with papillary stratified squamous epithelium, koilocytic dysplasia, parakeratosis, acanthosis, basal double-layer, loss of cellular polarity, nuclear hyperchromatism and pleomorphism, scattered mitosoid bodies, and a high degree of cytologic atypia. An immunohistochemical investigation for p53 and Ki67 showed staining of the basal and suprabasal layer, while p16 was strongly expressed in the nuclei of epithelial cells and Bcl-2 was positive only in mitosoid bodies and the lymphocytic inflammatory infiltrate. In situ DNA hybridization was negative for HPV. Oral BPap is an uncommon lesion in which the diagnostic process includes clinical, histopathological, and molecular correlations due to the similarity to aggressive behavior lesions such as BD.

Background Pancreatoblastoma (PBL) is a rare malignant pancreatic tumor seen predominantly in childhood, and its cytologic diagnosis remains challenging. Methods Twelve fine-needle-aspirations from 11 adults were analyzed. Results In total, 6 men and 5 women (median age, 45 years; age range, 32-60 years) had tumors measuring a median 5.6 cm (range, 2.5-12 cm) located in the pancreatic head (n = 7) or tail (n = 4), including 3 with familial adenomatous polyposis (FAP)/FAP-related syndromes and 4 with metastasis at diagnosis. The median follow-up was 39.8 months (range, 0.8-348 months), and 5 patients died of disease. The original cytology diagnoses were: PBL (n = 2), neuroendocrine neoplasm (n = 2), poorly differentiated neuroendocrine carcinoma (n = 2), well differentiated neuroendocrine tumor (n = 1), poorly differentiated carcinoma (n = 2), "positive for malignancy" (n = 1), acinar cell carcinoma (n = 1), and epithelioid neoplasm with endocrine and acinar differentiation versus PBL (n = 1). Universal cytopathologic findings included hypercellularity; 3-dimensional clusters; and single, monotonous, blast-like cells that were from 1.5 to 2.0 times the size of red blood cells with high nuclear-to-cytoplasmic ratio, fine chromatin, small, distinct nucleoli, and a resemblance to well differentiated neuroendocrine tumor and poorly differentiated neuroendocrine carcinoma. Branching pseudopapillae (n = 7) and grooved nuclei (n = 3) raised the differential diagnosis of solid-pseudopapillary neoplasm, but with more atypia. Uncommon features included pleomorphism (n = 4) and numerous mitoses (n = 1). Squamoid morules were seen on smears (n = 5) or cell blocks (n = 6) in 70% of patients and were characterized by epithelioid cells with elongated, streaming nuclei, fine chromatin, absent nucleoli, and positive nuclear β-catenin (n = 6 of 8). The median Ki-67 index was 21% (range, 2%-70%), and neuroendocrine marker expression was common (100%), but acinar markers were variable (63%). Conclusions A combination of cytologic findings in PBL, including a predominant population of primitive blast-like cells, subtle squamoid morules, frequent neuroendocrine and variable acinar phenotype, should facilitate accurate cytologic diagnosis and distinction from common mimics.

BackgroundLow-grade endometrial stromal sarcoma (ESS) is rare mesenchymal neoplasm, recently specified as harboringJAZF1–SUZ12rearrangement. TypicalJAZF1–SUZ12ESS is slow growing, in which high uptake of fluorodeoxyglucose (FDG) on positron emission tomography (PET) and subserosal masses are quite unusual.Case presentationA 69-year-old Japanese woman complained of urinary incontinence. Pelvic magnetic resonance imaging showed uterine lesions composed of (1) a 9 × 8 × 7-cm mass protruding from the right-anterior wall, (2) a 4.5-cm mass attached to the right-posterior wall, and (3) a 6.5-cm intramural mass in the fundus. FDG-PET demonstrated maximum standardized uptake value of 13.28 confined to the two subserosal masses (1 & 2) in contrast to no uptake of the intramural mass (3). She was diagnosed with a high-grade uterine sarcoma concomitant with leiomyomas and underwent total hysterectomy with bilateral salpingo-oophorectomy and pelvic lymphadenectomy. The removed uterus had three tumors—two in the right-anterior and right-posterior subserosa, respectively, and the remaining in the fundal myometrium. Microscopically, the three tumors shared morphologic features characterized by neoplastic cells similar to proliferative-phase endometrial stromal cells, in which neither round-cell component, pleomorphism, nor high mitotic activity was recognized. Nuclear cyclin D1 immunostaining was identified 50% of neoplastic cells in the two subserosal tumors (1 &2) whereas JAZF1–SUZ12gene fusion shared by the three uterine tumors and a focal tumor extension into the extrauterine vein. The patient is alive without evidence of recurrence at 14 months after surgery.ConclusionsPathologists and clinicians should not exclude the possibility ofJAZF1–SUZ12ESS even when uterine subserosal masses demonstrate extraordinary FDG uptake on PET. Molecular analysis is helpful for diagnostic confirmation ofJAZF1–SUZ12ESS with a complex growth pattern.

Neoplasms of salivary gland are an interesting diverse group of tumours. They form a fascinating subject for the head and neck surgeons. The relative infrequency combined with considerable histological and behavioral diversities and their regional anatomic relationship make them unusually interesting and challenging. The material of the study was obtained from 129 patients who underwent fine needle aspiration of the salivary glands during the period of two years. The smears were collected in the cytology laboratory. Medical College hospital. The clinical details were collected directly from the patients. The study confines itself to patients above the age of 12 years. The FNAC smear of the case diagnosed as carcinoma in pleomorphic adenoma showed large cell clusters having pleomorphism and vesicular nuclei with prominent nucleoli. The FNAC smear of the case diagnosed as chronic sialadenitis showed a cluster or lymphocytes and polymorphs.

Colorectal cancer is a major public health problem worldwide with increasing morbidity and mortality. Numerous exogenous and endogenous factors are involved in colorectal carcinogenesis: age, sex, diet, smoking, alcohol consumption, exposure to harmful environmental factors, intestinal microbiota, bacterial and viral infections, the ability of the host immune system to respond, genetic factors, etc. The present study analyzed histopathologically and immunohistochemically a number of 36 cases of colorectal adenocarcinomas. The existence of an accentuated cell pleomorphism was noted, which corresponds to different clones of tumor cells, in the same tumor coexisting aspects of tubular adenocarcinoma, mucinous areas and even signet-ring cell. The tumor stroma was mainly of the desmoplastic type, but also of the lax type, more or less infiltrated with inflammatory cells. Evaluation of immunomarkers for cancer stem cells (CSCs) showed that none of the markers used alone [cluster of differentiation (CD)133, CD44, aldehyde dehydrogenase 1 family member A1 (ALDH1A1), CD24, CD26] show CSCs.

Epithelioid hemangioma, otherwise known as angiolymphoid hyperplasia with eosinophilia, is a rare benign vasoproliferative disease with an unknown etiology. We report the case of a 42-year-old man with routine bloods test showing mildly elevated serum bilirubin level. CT scan revealed a lesion in the left liver lobe not typical of FNH. PET/CT scan and a dynamic liver MRI were consistent with a malignant mass. Surgical resection was performed. Histopathology of the 45 mm mass reported well-defined, slightly lobular proliferations of capillary-sized vessels around several central muscular vessels. Although the endothelial cells revealed a "hobnail" appearance, none of them showed pleomorphism or mitotic activity. Endothelial cells showed reactivity for the endothelial markers (CD34, CD31) and smooth muscle was detected in the blood vessel walls via immunohistochemistry. Despite its benign nature, epithelioid hemangioma of the liver can lead to a diagnostic and therapeutic dilemma due to the malignant looking features on imaging modalities.

BACKGROUND Epstein-Barr virus (EBV) is a DNA virus with oncogenic potential, especially in immunocompromised patients. EBV can promote smooth muscle proliferation, resulting in EBV-associated smooth muscle tumors (EBV-SMT). METHODS We report a case of a 10-year-old child with end-stage renal disease secondary to hypoplastic crossed and fused kidneys who underwent kidney transplantation. EBV serology was unknown for the donor and negative for the recipient; three months after he had a primary EBV infection. Two years after the transplantation, percutaneous nephrostomy was performed because of a drop in the estimated glomerular filtration rate and severe dilatation of the graft. Nephrography showed contrast enhancement of the pelvis of the graft kidney and proximal ureter, with a clear blockage at the level of the mid ureter and no passage towards the bladder. A 1.5-cm tumor was found causing intraluminal compression of the mid ureter. RESULTS Complete resection of the tumor and distal ureter was performed leaving a short proximal ureter. A tension-free uretero-ureteroanastomoses was achieved using the native ureter. There were no surgical complications. Histologic evaluation showed spindle-shaped muscle cells, moderate pleomorphism, and inflammatory infiltration. Immunohistochemical staining was positive for muscle-specific actin. Epstein-Barr encoding region (EBER) in situ hybridization was positive, confirming the diagnosis of EBV-associated SMT. CONCLUSIONS EBV-SMT is an exceedingly rare oncological entity that may develop in either the graft or any other organ. The clinical findings are location related. EBV seroconversion following transplantation might be a risk factor for the development of SMT in solid organ recipients.

Background Infantile myofibromas (IM) are benign soft tissue lesions of childhood and represent a significant portion of the benign spectrum of fibroblastic-myofibroblastic tumors. Cytological diagnosis of these tumors can be challenging because of overlapping morphology and limited case report descriptions. We describe the cytological features and the cytological differential diagnoses. Case report We describe cytological features of two IMs. The main features were the presence of loose clusters and dispersed bland myofibroblasts in varying stages of maturation with traversing blood vessels and myxoid stroma. The cells typically lacked features of atypia, mitoses and significant pleomorphism. Conclusion Diagnosis of IM on the basis of cytology alone can be tricky and definitive diagnosis should be made only after correlating the cytological features with histology. However, bland morphology of differentiating myofibroblasts can aid in cytological diagnosis and help to exclude other malignant spindle cells neoplasms needing preoperative chemotherapy.

Objective: Breast pathologies are very common in women. Breast cancer is the most common and most frequent cause of death in women. The most common type of breast cancer is invasive ductal carcinoma. Histopathological examination of the tissue taken with a fine needle aspiration biopsy or true-cut biopsy is the main diagnostic method when clinical examination of breast and/ or radiological mass is detected. The definitive diagnosis of benign and malignant lesions of the breast is important in the form of treatment. The most important features in the diagnosis of breast cancer are atypical cellular features such as invasion, desmoplasia, pleomorphism, hyperchromasia, nuclear irregularity, prominent nucleoli, high mitosis count. Loss of myoepithelial layer in the malignant cases is a very important feature in the diagnosis. Aim of this study is to evaluate the benign and malignant breast pathologies with the immunohistochemical panel. Material and Methods: 52 breast true-cut biopsy materials in the archives of Department of Pathology at Faculty of Medicine, Erzincan Binali Yıldırım University between 2015-2017 were re-examined with the immunohistochemical panel. The immunohistochemical staining markers such as estrogen, progesterone, cerb-B2, E-cadherin, P63, CD10, calponin, CK5/6 have been applied in all cases. Results: 23 cases were a benign disease such as fibroadenoma, adenosis, fibrosis, fibrocystic changes, and intraductal papilloma. 29 cases were a malignant epithelial tumor. Conclusion: In the diagnosis of breast cancers, mainly cellular properties are determinative. The evaluation with the immunohistochemical panel will reduce the risk of diagnostic error when the cases that difficultly diagnosed with cellular properties.

We report a case of anaplastic PXA for which histological study and molecular analysis were performed at the time of the first resection and two recurrences. A 15-year-old girl had a temporal lobe tumor that had been followed as a cystic lesion from three years of age without histopathological examination. The first and second surgical specimens exhibited typical histological features of PXA such as nuclear and cytoplasmic pleomorphism. In addition, microvascular proliferation was observed in the second surgical specimen. On the other hand, nuclear pleomorphism was unclear in the third surgical specimen and it was mainly composed of spindle cells. Palisading necrosis was observed. Mitotic figures and the Ki-67 proliferation index gradually increased. BRAF V600E and TERT promoter mutation were detected in the first, second, and third surgical specimens. In addition, PTEN mutation and CDNK2A deletion were detected in the third surgical specimen. Considering the histopathological and genetic changes over time, we concluded that our case of anaplastic PXA underwent malignant progression.

Progestin usage can alter the histologic and cytologic features of HSIL, which may potentially lead to the under-diagnosis of this precancerous lesion. The objective of the present study was to assess the relationship between the usage of progesterone-based contraceptives and the cytologic features of high-grade squamous intraepithelial lesion (HSIL) of the cervix. In this case-control study, we assembled 46 cases of cervical HSIL (CIN 3), including samples from 26 patients with known history of progestin usage (study group) and 20 samples from patients with no history of any exogenous hormone usage (control group). Cell image analysis was performed on all samples using a proprietary software. Immunohistochemical studies for Ki67, p16, estrogen receptor and progesterone receptor were performed on all cases, as was RNA in situ hybridization for HPV subtypes 16 and 18. Compared with the control group cases, the average nuclear size (21.5±1.80 μm) and the nuclear: cytoplasmic ratio (0.28±0.015) of HSILs in the study group cases were significantly smaller (P=0.026) and reduced (P=0.005), respectively. In addition, the study group cases showed reduced nuclear atypia and pleomorphism and significantly reduced mitotic figures (1.74±1.86/mm in study group versus 5.94±1.3/mm in control group, P

The cell division cycle 73 gene is mutated in familial and sporadic forms of primary hyperparathyroidism, and the corresponding protein product parafibromin has been proposed as an adjunct immunohistochemical marker for the identification of cell division cycle 73 mutations and parathyroid carcinoma. Here, we present data from our experiences using parafibromin immunohistochemistry in parathyroid tumors since the marker was implemented in clinical routine in 2010. A total of 2019 parathyroid adenomas, atypical adenomas, and carcinomas were diagnosed in our department, and parafibromin staining was ordered for 297 cases with an initial suspicion of malignant potential to avoid excessive numbers of false positives. The most common inclusion criteria for immunohistochemistry were marked tumor weight (146 cases) and/or fibrosis (77 cases) and/or marked pleomorphism (58 cases). In total, 238 cases were informatively stained, and partial or complete loss of nuclear parafibromin immunoreactivity was noted in 40 cases; 10 out of 182 adenomas (5%), 27 out of 46 atypical adenomas (59%), and 7 out of 10 carcinomas (70%), with positive and negative predictive values of 85 and 90%, respectively for the detection of atypical adenomas/carcinomas versus adenomas, and 18 and 98%, respectively for carcinomas versus atypical adenomas/adenomas. Male patients with high-proliferative tumors were overrepresented among cases with aberrant parafibromin immunohistochemistry, and carcinomas more frequently harbored parafibromin aberrancies than atypical adenomas and adenomas (p

Context Invasive micropapillary adenocarcinoma (MPC) is an aggressive variant of lung adenocarcinoma, frequently manifesting with advanced stage lymph node metastasis and decreased survival. Objective Identification of this morphology is important, as it is strongly correlated with poor prognosis regardless of the amount of MPC component. To date, no study has investigated the morphological criteria used to objectively diagnose it. Design Herein, we selected 30 cases of potential MPC of lung, and distributed 2 digital images per case among 15 pulmonary pathology experts. Reviewers were requested to diagnostically interpret, assign the percentage of MPC component, and record the morphological features they identified. The noted features included: columnar cells, elongated slender cell nests, extensive stromal retraction, lumen formation with internal epithelial tufting, epithelial signet ring-like forms, intracytoplasmic vacuolization, multiple nests in the same alveolar space, back-to-back lacunar spaces, epithelial nest anastomosis, marked pleomorphism, peripherally oriented nuclei, randomly distributed nuclei, small/medium/large tumor nest size, fibrovascular cores, and spread through air-spaces (STAS). Results Cluster analysis revealed three subgroups with the following diagnoses: “MPC”, “combined papillary and MPC”, and “others”. The subgroups correlated with the reported median percentage of MPC. Intracytoplasmic vacuolization, epithelial nest anastomosis/confluence, multiple nests in the same alveolar space, and small/medium tumor nest size were the most common criteria identified in the cases diagnosed as MPC. Peripherally oriented nuclei and epithelial signet ring-like forms were frequently identified in both the “MPC” and “combined papillary and MPC” groups. Conclusions Our study provides objective diagnostic criteria to diagnose MPC of lung.

Objective Synovial sarcomas (SS) are rare soft tissue tumours defined by the SYT-SSX fusion gene. The tumours are composed of mesenchymal cells with varying degrees of epithelial differentiation. Cytomorphological descriptive studies are limited to small series and single cases. In this study we systematically examined the cytological features of SS diagnosed at our institution. Methods SS diagnosed by fine-needle aspiration (FNA) cytology at our institution between 2006 and 2018 were reviewed by a panel of senior cytopathologists. Clinical and cytopathological characteristics were categorised and described. Results A total of 38 SS FNAs were identified from 35 patients. The cytomorphology was uniform, presenting as highly cellular smears of clusters and individual cells with mixed round, oval and spindle cells. We frequently observed pericapillary arrangement and occasionally pink background stroma was seen. Glandular formation or epithelial components were identified in the majority of cases which on histology were subtyped as biphasic SS. Pleomorphism and mitoses were rare. Immunocytochemical analysis was frequently positive for vimentin, epithelial membrane antigen, Bcl2 and, in recent cases, TLE1. Pan-cytokeratins and CK7 could occasionally be positive in biphasic cases. The diagnostic SYT-SSX fusion gene was detected in all FNA specimens using polymerase chain reaction or fluorescence in situ hybridisation. Conclusions SS have distinct and uniform cytopathological features. Molecular genetic analysis for SYT-SSX are invaluable for diagnosing SS with FNA and should be implemented in cytopathological laboratories that routinely perform soft tissue diagnostics.

Purpose: To reveal the effect of cigarette smoking on corneal endothelial cells. Patients andmethods: this is a case control cross sectional study including 99 persons, 61 chronic cigarettesmokers and another age matched 38 control nonsmokers. Parameters used in our study werecell density (CD), polymegethism, pleomorphism, the average of cell size, and central cornealthickness (CCT). Results: The mean values of the CD were 2829.9±334.9 compared to3243.6±237.9, CV were 44.13±9.73 compared to 32.84±2.97, HEX were 40.44±6.95% compared to60.11±5.83% for smokers and non-smoker groups respectively, with a highly statistically significantvalue (p

Background: Superficial myofibroblastoma (SMF) is a very rare benign mesenchymal tumor in the female lower genital tract. Only 46 cases have been reported in the English language literature, among which only 7 cases arose in the vulva. Sometimes SMF histologically mimics aggressive angiomyxoma (AA) in which massive myxoid change in stroma is characteristic. We herein report a case of vulvar SMF with prominent myxoid stroma and review the literature with the emphasis on the differential diagnosis of SMF and AA. Case presentation: a 37-year-old woman presented with a painless mass in the vulva. Magnetic resonance imaging (MRI) showed a well-circumscribed 7 cm mass in the subcutis of the vulva. The tumor was resected. Histopathologically, the tumor was characterized by sparsely populated spindle-shaped cells in the fibromyxoid stroma. Thin-walled blood vessels were detected. Mitoses or pleomorphism was not found. Tumor cells were positive for vimentin, ER, PgR, and desmin. Some cells were positive for alpha-SMA and CD34. All cells were negative for S100 protein. Conclusions: because SMF and AA show different clinical prognoses, distinguishing SMF from AA is important. However, SMF may share many common histological features with AA: superficial localization (above fascia), sharp borderline from adjacent tissue, expansive growth pattern; a specific vascular pattern will lead to an accurate diagnosis of SMF. Familiarization with the histological characteristics of the two entities will help to make a prognostic prediction.

Background: Ocular medulloepithelioma (OM) is a rare ocular malignancy. This is a report of a rare case of medulloepithelioma that was misdiagnosed as retinoblastoma. Material and methods: A case report and review of published, peer-reviewed, English language literature reporting on ocular medulloepithelioma. Results: A seven-year-old girl presented with a white mass in the anterior chamber of her left eye. The initial diagnosis was retinoblastoma with anterior chamber invasion, and therefore it was enucleated. Microscopy showed a cellular tumour composed of malignant primitive cells forming sheets, rosettes, and tubular structures. Based on the presence of prominent pleomorphism the tumour was diagnosed as malignant teratoid medulloepithelioma. At last date of follow-up three years after enucleation, the patient was alive without metastasis. A systematic review of literature, analysed 177 cases of OM. The tumour was localised in the ciliary body in 134 (92%) cases, and 26 (23%) cases had extraocular extension. Primary management was enucleation in 84 (55%) cases, tumour resection in 32 (21%) cases, and radiation therapy in 20 (13%) cases. Histopathology disclosed benign features in 36 (22%) eyes, malignant features in 124 (78%) eyes, teratoid features in 72 (59%), and non-teratoid features in 51 (41%) eyes. At a mean follow-up of five years, 14 (8%) patients had metastasis, and six (6%) patients were dead. Conclusions: Ocular medulloepithelioma most commonly affects children. The most common type is the malignant teratoid type, but it has a favourable prognosis, and distant metastasis and mortality are relatively rare, at 8% and 6%, respectively.

Background: Diabetic eye disease is an end-organ response to the effects of the condition on the human system. The cornea is a transparent structure protecting the anterior one-sixth of the eye. Chronic hyperglycemia can affect the corneal layers shape and functions that responsible for corneal transparency. Objectives: Comparison of the changes in corneal endothelium namely, cell density (CD), percentage polymegathism, cell volume (CV) and pleomorphism (6A) along with central corneal thickness (CCT) in patients of type 2 diabetes mellitus with normal age and sex- matched subjects. Patients and methods: A case-control study in Sayed Galal University Hospital. 20 eyes of type 2 diabetic patients and 20 eyes of age and sex matched controls were included in the study. Age, gender, other demographic data, and relevant diabetic history were obtained. Full evaluation of both cases and controls including both anterior and posterior segment complete evaluation was done. Non- contact specular microscopy was used to study the corneal endothelial cells. Results: The mean endothelial cell density (ECD) was non-significantly lower in type 2 diabetics compared to controls (p value = 0.751.). There was a highly significant reduction in hexagonally in the cases compared to controls and highly significant increase in coefficient of variation in the cases compared to controls Conclusion: This study acknowledged that type 2 diabetes causes a significant decrease of hexagonality and increase CV (polymegathism). However, non-significant reduction of ECD was documented

Early-onset Fuchs endothelial corneal dystrophy (FECD) has been associated with nonsynonymous mutations in collagen VIII α2 (COL8A2), a key extracellular matrix (ECM) protein in Descemet’s membrane (DM). Two knock-in strains of mice have been generated to each express a mutant COL8A2 protein (Col8a2(L450W/L450W) and Col8a2(Q455K/Q455K)) that recapitulate the clinical phenotype of early-onset FECD including endothelial cell loss, cellular polymegathism and pleomorphism, and guttae. Due to abnormalities in ECM protein composition and structure in FECD, the stiffness of DM in Col8a2 knock-in mice and wildtype (WT) controls was measured using atomic force microscopy at 5 and 10 months of age, coinciding with the onset of FECD phenotypic abnormalities. At 5 months, only sporadic guttae were identified via in vivo confocal microscopy (IVCM) in Col8a2(Q455K/Q455K) mice, otherwise both strains of Col8a2 transgenic mice were indistinguishable from WT controls in terms of endothelial cell density and size. By 10 months of age, Col8a2(L450W/L450W) and Col8a2(Q455K/Q455K) mice developed reduced corneal endothelial density, increased endothelial cell area and guttae, with the Col8a2(Q455K/Q455K) strain exhibiting a more severe phenotype. However, at 5 months of age, prior to the development endothelial cell abnormalities, Col8a2(L450W/L450W) and Col8a2(Q455K/Q455K) mice knock-in mice had reduced tissue stiffness of DM that was statistically significant in the Col8a2(Q455K/Q455K) mice when compared with wildtype controls. These data indicate that alterations in the tissue compliance of DM precede phenotypic changes in endothelial cell count and morphology and may play a role in onset and progression of FECD.

Subependymoma is a rare tumor of the central nervous system, representing 0.2 to 0.7% of all intracranial tumors. They are usually found in the fourth ventricle or in the walls of the lateral ventricles, often remaining asymptomatic. Subependymomas occur rarely in the cervical or thoracic spinal cord. Since its first description in the spinal cord by Boykin et al in 1954, only 47 cases have been reported. A 49-year-old man presented with a 4-year-long-lasting neck pain, which radiated to the upper right extremity for 4 years. It was insidious at onset and revealed gradual progression, difficulty in performing fine hand movements, and hyperalgesia. Magnetic resonance imaging revealed irregular hyperintensity of T2 and dilatation of the spinal cord from C4 to T1 with associated edema and an intramedullary lesion with central location. During the surgical event, a transoperative biopsy was performed that revealed loose fibrillary networks and groups of nuclei showing mild pleomorphism and microcystic formations. Histologically, we observed groups of cells with mild nuclear pleomorphism embedded in a dense, thin, glial fibrillar fundus, and microcystic formations. Immunohistochemical staining revealed diffuse positivity for the glial fibrillary acidic protein, and negative for the epithelial membrane antigen. Subependymoma accounts for 8.3% of all ependymal tumors. There are few descriptions of the cytologic features of the subependymoma because this neoplasm is rare and most commonly found incidentally in autopsies.