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Papillary thyroid carcinoma (PTC) is the most common type of thyroid carcinoma that carries a favourable prognosis. However, a small subset unfortunately shows transformation to least differentiated anaplastic carcinoma (AC) having a highly aggressive behavior. This process usually occurs within thyroid but is rare in metastatic cervical lymph node or soft tissue neck and exceedingly rare at distant sites. We report a unique case of a 75 years female who presented with anaplastic carcinoma in metastatic neck deposit with occult papillary thyroid carcinoma. To the best of our knowledge, this is the first case in the world literature having anaplastic transformation (AT) in the metastatic neck deposit, right at the presentation with a totally unnoticed PTC clinically. We present this case to emphasize that the transformation process can occur even when the differentiated malignancy in thyroid is small, insignificant or hidden and that metastasis solely can be the presenting feature which can be misleading clinically and even histopathologically. As AC is very aggressive, there is need for early and precise diagnosis & prompt therapeutic intervention. Keywords: Anaplastic carcinoma, Transformation, Papillary thyroid carcinoma, Dedifferentiation, Immunohistochemistry

Recent reports have highlighted a lower-than-expected prevalence of neoplasia in elephants and suggested mechanisms for cancer resistance. But despite infrequent reports in the literature, uterine neoplasia is common in managed Asian elephants ( Elephas maximus). This study is an archival review of reproductive tract neoplasia in 80 adult female Asian elephant mortalities in managed care facilities in the United States from 1988 to 2019. Neoplasms occurred in 64/80 (80%) of cases. Most were in the uterus (63/64; 98%) with only a single case of ovarian neoplasia. Myometrial leiomyomas were present in 57/63 (90%) cases with uterine neoplasia. Uterine adenocarcinoma was present in 8/63 (13%) cases. Remaining cases included endometrial adenoma (2), focal carcinoma in situ in endometrial polyps (1), anaplastic carcinoma (1), endometrial hemangioma (1), primitive neuroectodermal tumor (PNET; 1), and angiosarcoma (1). One case with uterine adenocarcinoma had a separate pelvic mass histologically characterized as an anaplastic sarcoma. Distant metastases were documented in 5/8 (63%) cases of uterine adenocarcinoma, and in the uterine anaplastic carcinoma, PNET, and angiosarcoma. Four uterine adenocarcinomas and one carcinoma in situ were examined immunohistochemically for pan-cytokeratin, vimentin, and estrogen receptor. In all, neoplastic cells were pan-cytokeratin positive and vimentin negative, and in 2 cases were immunoreactive for estrogen receptor. Results show that female reproductive tract neoplasia, particularly of the uterus, is common in Asian elephants and is not limited to leiomyomas. Importantly, uterine neoplasms have the potential to impact fecundity and may represent obstacles to conservation in managed care.

A 75-year-old man visited our hospital for the examination of a tumor in the pancreas. Computed tomography showed an 85×85-mm low-density tumor in the pancreas. The tumor was pathologically diagnosed as poorly differentiated carcinoma by endoscopic ultrasound-guided fine-needle aspiration. Although we started chemotherapy, the patient died 84 days after the diagnosis. An autopsy demonstrated a ruptured anaplastic carcinoma with mucoepidermoid carcinoma of the pancreas. Anaplastic carcinoma with mucoepidermoid carcinoma is a very rare histologic subtype of pancreatic carcinoma, so pathological findings are important for predicting the patient's prognosis. Physicians should be aware of this rare but fatal disease.

Canine mammary carcinoma (CMC) is the most common type of neoplasm in intact female dogs. While a previous study in Western countries validated the 2011 classification as an independent prognostic indicator in CMC, its role in CMC prognostication in Asian countries such as Korea remains unclear. In the present study, we estimate the survival rates in CMC types defined by the 2011 classification, elucidate the prognostic significance of the histological subtype and grade and that of the lymphatic invasion status in CMC, and validate the 2011 classification as an independent prognostic indicator in a large cohort of CMCs (excluding cases of multicentric CMCs). A total of 155 CMC cases retrieved from archived formalin-fixed, paraffin-embedded tissues, along with 2-year follow-up data, were retrospectively analysed. A significant association was found between the histological subtype of the 2011 classification and the tumour-specific survival. Carcinosarcoma, adenosquamous carcinoma and anaplastic carcinoma subtypes were associated with the poorest prognosis. Dogs with comedocarcinoma and solid carcinoma followed a disease course that was more aggressive than that observed in dogs with a carcinoma arising in a benign mixed tumour. Moreover, age, histological grade and lymphatic invasion status significantly correlated with tumour-specific survival in univariate analysis. In multivariate analysis, histological subtype, age and lymphatic invasion status remained independent prognostic factors for CMC.

Low back pain (LBP) is one of the most important health conditions that can affect human with physical and psychosocial changes. Nonspecific LBP, defined as self-limiting and which exact cause cannot be determined, is common among older adults. Besides, lumbar disc herniation should be the first diagnosis that comes to mind in between 40–60 years-old patients with clinical findings of radiculopathy with LBP. However, in order not to miss important causes such as malignancy that can cause LBP, the patient's anamnesis should be deepened, and physical examination should be performed carefully. We reported the case of a 53-year-old woman with anaplastic carcinoma of the pancreas (APC) where the initial symptom was LBP accompanied by radiculopathy and diagnosed by tru-cut biopsy from the sacral metastatic soft tissue mass, which was specified by the advanced imaging. APC is a rare cancer, and the survival time of the patients is quite short due to its rapid spread and resistance to chemotherapy and radiotherapy. Based on this case, clinicians should evaluate the patient detailly, prefer further imaging when necessary, and discuss the case with musculoskeletal radiologists when there are diagnostic problems, which will reduce the possibility of overlooking the underlying serious causes of LBP.

Background Undifferentiated carcinoma (UC) of the pancreas has been considered a highly aggressive malignancy. However, only a few studies have systematically described the clinical course of UC patients. The aim of this study was to clarify the prognosis and construct a prognostic model for patients with unresectable UC. Methods This study was conducted at 17 institutions in Japan, and a total of 55 patients were analyzed. Results The median overall survival (OS) of patients with unresectable UC was 3.95 months. In the multivariate Cox proportional hazards (CPH) model, age ≥65 years, Eastern Cooperative Oncology Group performance status (ECOG PS) ≥2, and C-reactive protein (CRP) >10 mg/L were independent prognostic factors for OS (age ≥65 years: hazard ratio [HR], 2.732; 95% confidence interval [CI], 1.353–5.515; ECOG PS ≥ 2: HR, 7.866; 95% CI, 1.981–31.241; CRP >10 mg/L: HR, 1.956; 95% CI, 1.013–3.775). Based on the β coefficients from the CPH model, the prognostic scores were defined as follows: age ≥65 years (3 points), ECOG PS ≥ 2 (6 points), and CRP >10 ml/L (2 points). The final prognostic model was the sum of the points. The derived prognostic model stratified patients into high-risk (score ≥4) and low-risk (score 0–3) groups, with significant differences in OS (1.45 vs. 8.19 months, respectively; p Conclusions The prognostic model stratified patients into high-risk and low-risk groups. These findings suggest that this model can serve as a tool for patient information and decision-making with regard to the therapeutic strategy for UC.

Objective: To determine the complications associated various types of tumors of advanced stage of thyroid disease at tertiary care hospital. Study Design: Descriptive study. Place and Duration: Two years study from April 2018 to March 2020 was conducted in Liaquat University of Medical and health sciences Jamshoro. Patients and Methods: All patients were admitted from Outpatient department (OPD) with advance stage of tumor of thyroid and either of gender were included. The patients were evaluated fully after history and clinical examinations berries sign and specific investigations of thyroid profile (T3,T4,TSH), ultrasound of thyroid, fine-needle aspiration cytology FNAC, image guided biopsy, frozen section biopsy for confirmation of diagnosis, indirect laryngoscopy, x - Ray neck and MRI. All the patients were assessed for pre-operative evaluation (complications) with advanced stage of thyroid tumors. All the data regarding developed complications was recorded via study proforma. Data was analyzed by using the SPSS version 20. Results: Most of the patients were found with age groups of 20 to 34 years and 35 to 55 years. Out of all, 25 patients were diagnosed papillary carcinoma, 12 patients were diagnosed as follicular carcinoma, 7 patients had Anaplastic carcinoma, 4 patients were diagnosed lymphoma and 2 patients were diagnosed as medullary carcinoma. As per complications of advanced disease 23 patients had thyroid swelling with cervical lymphadenopathy and pain, 13 patients had thyroid swelling with change of voice, 7 patients had thyroid swelling with dyspnea and dysphagia, 5 patients were presented with thyroid swelling with bony pain, weight loss and pathological fractures, 2 patients were presented with thyroid swelling with diarrhea. Conclusion: Various complications such as swelling, pain, hemorrhage, cervical lymphadenopathy, change in voice, weight loos, pathological fracture, dyspnea and dysphagia were frequently seen in patients presented with advanced stage of thyroid disease.

Background: Thyroid cancer is the leading cause of death both in developing and developed countries. Patients present with enlarged thyroid. Radiology shows hot and cold nodules. Thyroidectomy or lobectomy is done to rule out malignancy. Objective: To determine the incidence of thyroid carcinomas and other pathologies in thyroidectomy specimen of different age group patients presenting with clinically enlarged thyroid. Study Design: Cross-sectional study. Settings: Department of Histopathology, Foundation University Medical College (FUMC), Islamabad and Department of surgery, Fauji Foundation Hospital (FFH), Rawalpindi Pakistan. Duration: from Jan 2012 to March 2019. Methodology: All the thyroidectomies specimens send from Surgery department of FFH to Histopathology Department of FUMC during study period and fulfilling the pre-set criteria were included in the study. All the data and results were analyzed using SPSS version 17.0. Results: Out of 500 total patients, 89% (n=445) were diagnosed as having multinodular goiter, 2.6% (n=13) thyroiditis, 2.2% (n=11) follicular adenoma, 0.8% (n=4) Hurthle cell adenoma, 0.2%(n=1) hyalinizing trabacular adenoma and thyroid carcinomas. The carcinomas comprised 2.6%(n=13) papillary carcinoma, 0.8%(n=4) poorly differentiated carcinoma,0.8%(n=4) anaplastic carcinoma,0.6%(n=3) medullary carcinoma and 0.4%(n=2) follicular carcinoma. In 445 patients of multinodular goiter 158 patients were in the age range of 41-50 years, in 13 cases of thyroiditis 7 were in the age range of 31-40 years, in 11 cases of follicular adenoma 4 patients were in the age range of 31-40 years, in 4 cases of hurthle cell adenoma 3 patients were in the age range of 41-50 years, in 13 cases of papillary thyroid carcinoma 5 patients were in the age range of 31-40 years, in 4 cases of poorly differentiated carcinoma 2 patients were in the age range of 41-50 years and in 4 cases of anaplastic carcinoma 2 patients were in the age range of 61-70 years. Conclusion: The study concluded that thyroid carcinomas collectively constituted 5.20% of the study cases. Papillary carcinoma was the most frequent malignant neoplasm constituting 2.6 % and occurring mostly in the age range of 31-40 years, while anaplastic carcinoma comprised of 0.8% of malignant lesions occurring in the age range of 61-70 years. The most frequent cause of thyroid enlargement was multinodular goiter (89%) with majority of the patients in the age range of 41-50 years.

Most anaplastic thyroid carcinomas (ATCs) arise from papillary thyroid carcinoma (PTC). This process is also called anaplastic transformation, and the morphological harbingers of this phenomenon in nodal recurrence have not been assessed systematically. For this reason, the current study focused on features of 10 PTCs with regional lymph node recurrence that was accompanied with disease progression due to anaplastic transformation in at least one of the nodal recurrences. The findings of additional 19 PTCs which recurred without anaplastic transformation after ≥ 10 years of follow-up served as the control group. There were no clinicopathological differences between the two groups at initial surgery including age, gender, tumor size, lymph node metastasis, distant metastasis, extrathyroidal extension, histologic subtype, and treatment. The median time from the initial thyroid surgery to anaplastic transformation in the nodal recurrence was 106 months (range 6 to 437 months). Mutational analyses showed recurrent PTCs with anaplastic transformation had a high prevalence of BRAFV600E mutation (8/9) and TERT promoter mutation (9/9), both of which were detected in primary tumors. PIK3CAH1047R mutation was detected in one case. No case had RAS mutation. Nineteen recurrent PTCs without anaplastic transformation harbored BRAFV600E mutation and seventeen of these had TERT promoter mutation. Unlike primary tumors with subsequent nodal anaplastic transformation, TERT promoter mutation was only present in the metastatic nodal recurrence from 4 patients without transformation. No patients had neither high-grade features (necrosis and increased mitotic activity) nor solid/insular growth or hobnail cell features in their primary tumors. In the group of patients with transformation, 3 had solid/insular growth in the lymph node metastasis at the time of primary tumor resection (one displaying nuclear features of PTC and solid growth with increased mitotic activity, one with insular component consistent with poorly differentiated carcinoma component, and one displaying nuclear features of PTC and solid growth), and additional 2 patients had solid/insular growth with no high-grade features or poorly differentiated carcinoma component at the time of subsequent nodal recurrence prior to anaplastic transformation. Hobnail cell features were exclusively seen in subsequent metastatic lymph nodes prior to anaplastic transformation. The control group lacked solid/insular growth and hobnail cell features in the metastatic nodal disease. Aberrant p53 expression and loss of TTF-1 featured tumor components with anaplastic transformation. This series identified a subset of recurrent PTCs with TERT promoter mutation was prone to undergo anaplastic transformation, and that solid/insular growth and hobnail cell features were morphological predictors of anaplastic transformation in the nodal recurrence.

Introduction: The neutrophil-to-lymphocyte ratio (NLR) reveals the balance of immune system is and associated with survival in various type of cancers. Tyrosine kinase inhibitors (TKI) improve patient survival with progressing thyroid cancer and are said to have less side effects, and are considered good palliation. Objective: This study evaluated the time series behavior of NLR in advanced thyroid carcinoma patients on TKI therapy and examined what percentage of patients received TKIs in the last month of life. Methods: We retrospectively reviewed medical records on 72 patients with advanced thyroid carcinoma treated with TKIs between May 2015 and October 2018. All patients had progressive disease and/or uncontrolled distant metastasis. Fifty-two patients had differentiated thyroid carcinoma (DTC), 19 patients had anaplastic carcinoma (ATC), and 1 had squamous cell carcinoma. NLR was calculated as the absolute neutrophil count divided by the absolute lymphocyte count. Median follow-up time in DTC and ATC patients was 12.3 months (range 0.9–40.4) and 2.7 months (range 0.6–14.3), respectively. Results: In DTC patients, median NLR at initial treatment, at initiation of TKI, and for 20 patients who died at the time of death was 2.25 (range, 0.89–9.78), 3.55 (range, 0.86–28.3), and 11.78 (range, 0.98–98.0), respectively. In ATC patients, median NLR at initial treatment, at initiation of TKI, and for 16 patients who died at the time of death was 2.96 (range, 1.12–9.0), 11.43 (range, 2.32–95.0), and 16.9 (range, 3.45–95.0), respectively. NLR >10 at TKI initiation was significantly associated with shorter overall survival compared with NLR p < 0.0001) in DTC patients. Among 46 dead patients, 32 patients (68.1%) received TKIs treatment in the last month of life (85% DTC patients and 61.5% ATC patients). In receiver operating characteristic curve analysis, cutoffs for DTC and ATC were 11.43 (p = 0.0488, area under the ROC curve 0.941) and 31.67 (p = 0.0034, area under the ROC curve 0.831) in patients who survived ≤6 weeks and >6 weeks, respectively. Conclusion: A substantial percentage of patients received TKIs in the last month of life. The NLR increased according to tumor progression and predicted survival after TKI initiation. We might refer the patients with NLR >11.43 in DTC and those with NLR >31.67 in ATC to a hospice/palliative care program.

Thyroid squamous cell carcinoma is very rare. At present, it is limited to case reports. Since the thyroid follicular epithelium is the non-squamous epithelium, how primary squamous cell carcinoma (SCC) of the thyroid occurs is still a controversial issue. Hashimoto’s thyroiditis (HT) is considered to be an independent risk factor for thyroid cancer, under the basis of HT, how tumor cells evolve and develop to papillary thyroid carcinoma (PTC), and particularly to de-differentiate into SCC is elusive. We report a 72-year-old female patient who developed multiple subtypes of PTC on a basis of HT, and finally to de-differentiate into SCC within the local foci of lymph node metastasis. We found that there was a variety of sub-types of PTC in this patient in the background of HT. SCC was found within local lymph node metastasis. Pathomorphology, immunohistochemistry, and molecular pathology have confirmed that the SCC was derived from PTC, and then developed into poorly differentiated SCC and/or anaplastic carcinoma. We also conducted a comprehensive literature review.

Introduction: Thyroid lesions are fairly common & have a wide spectrum of diseases ranging from functional, immune mediated to neoplastic lesions. Objectives: 1) To study the occurrence of various lesions of the thyroid. 2) To study and correlate clinico-morphological features. Results/ Observation: All thyroidectomy specimens were included in the study period of two years i.e, from January 2009 to December 2010. A total of 120 specimens were studied by routine paraffin processing and heamatoxylin eosin stain. Detailed histopathological study was done and correlated with age, sex & clinical presentation. Out of 120 cases, non-neoplastic lesions accounted for 83.33% and included thyroglossal duct cyst (2.5%), Hashimoto thyroiditis (9.1%), colloid goitre (29.1%) & multinodular goitre (42.5%). Neoplastic lesions accounted for 16.67% and consisted of follicular adenoma (12.5%) as the only benign lesion. Papillary carcinoma (2.5%), medullary carcinoma (0.83%) and anaplastic carcinoma (0.83%) were malignant lesions found. Conclusion: Thyroid lesions predominantly affects females during 3rd and 4th decades of life and commonly present as neck swelling. Multinodular goitre was the commonest non- neoplastic lesion followed by colloid goitre. Follicular adenoma was the only benign neoplasm seen while papillary, medullary and anaplastic carcinoma were the malignant thyroid neoplasms. Keywords: Thyroid lesions, Non- neoplastic and neoplastic lesions.

Background Anaplastic thyroid carcinoma (ATC), a highly aggressive malignancy, has no effective treatment to date. Trophoblast cell-surface antigen 2 (TROP-2), a transmembrane glycoprotein, has been suggested to be a promising novel target for sacituzumab govitecan, an antibody-drug conjugate. 5-Hydroxymethylcytosine (5hmC) has a role in tumor suppression and promoting modification. Additionally, isocitrate dehydrogenase 1 (IDH1) mutations are strongly associated with increased overall survival in gliomas and worse prognosis in leukemias. This study attempts to evaluate the immunoexpression of TROP-2, 5hmC, and IDH1 in ATCs and to determine their potential impact in targeted therapy. Methods Twenty-four ATCs were retrieved, with 9 cases that occurred de novo and 15 cases derived from either papillary thyroid carcinoma (PTC) or follicular thyroid carcinoma (FTC). Sections were immunostained with TROP-2, 5hmC, and IDH1 antibodies, and evaluated using the QuPath program. The t tests were performed using SPSS software. Results TROP-2 was detected in 12 ATCs with 9 cases demonstrating a high expression and in all PTC components, and absent in all FTC components of secondary ATCs. 5hmC expression was moderately reduced in PTC and FTC components and markedly reduced in ATC. The entire cohort showed a total absence of IDH1. Conclusions Increased TROP-2 immunoexpression in some ATCs supports that these patients may potentially benefit from an antibody-drug conjugate therapy targeting TROP-2. Markedly reduced 5hmC expression suggests that 5hmC may be used as potential therapeutic targets for ATC. The total lack of IDH1 R132H mutation by immunostain indicates that it has no prognostic and therapeutic value in ATC.

Anaplastic pancreatic carcinoma is a very rare histological subtype of pancreatic cancer, which is characterized by a more aggressive course than for conventional ductal adenocarcinoma. In this article, we consider the features of the clinical course, the difficulties of diagnosis in connection with the absence of pathognomonic signs of pancreatic cancer, and the morphological picture of this disease in a patient 60 years of age. This clinical case clearly demonstrates the complexities of the pancreatic carcinoma diagnosis, fast disease progression, and extremely unfavorable prognosis. It is important for clinicians to remember that this pathology often has a subclinical course, and the oncomarker levels are not always true.

Introduction Multinodular goiter is defined as multiple discrete nodules in the thyroid gland. The incidence of Papillary carcinoma thyroid was found to be highest out of total Multinodular Goiter cases while that of Anaplastic carcinoma was the least. We report a rare coexistence of Papillary carcinoma and Anaplastic carcinoma in adult patient with a long-standing Multinodular Goiter. Case presentation Here we present a case of 54 years male with huge anterior neck swelling for 20 years with a gradual increase in size. Computerized tomography of neck revealed solidocystic mass lesion without any significant lymphadenopathy, features suggesting Multinodular goiter with differential diagnosis of Carcinoma Thyroid. Cytological examination showed Papillary thyroid Carcinoma. He underwent total thyroidectomy with central neck dissection. Postoperative period was uneventful. Histopathological report revealed features suggestive of mixed tumor of Papillary thyroid Carcinoma and Anaplastic Carcinoma thyroid TNM Staging T3 N0 M0, Stage IVA. After the final reports patient was sent for adjuvant therapy three weeks later where he received megavoltage external beam radiation and he was followed up till 12th week. He was assessed radiologically which showed no signs of physical progression of the disease. However, he was lost to follow up after that visit. Discussion Long-standing benign conditions of thyroid can transform into malignant forms in the undefined duration of time. Conclusion Regular follow up and early management of multinodular goiter at the right time can save a patient from undue stress and complication like the conversion into malignancy.

Background Lung cancer tumorigenesis is mainly due to accumulation of genetic and epigenetic events in the respiratory epithelium. Epigenetic alteration is more frequent than somatic mutation in lung cancer. CpG island methylation of homeobox-associated genes is commonly seen in most early stage tumors. This study aimed at examining the potential usefulness of DNA methylation biomarker SHOX2, in broncho-alveolar lavage, in the diagnosis of lung cancer. Broncho-alveolar lavage was obtained from 80 patients; 60 cases with lung masses (proved malignant by histopathology) and 20 age and gender matched patients with benign lung lesions (benign controls). SHOX2 methylation status was evaluated using methylation analysis by restriction endonuclease digestion and real-time PCR. Results SHOX2 methylation level ranged 3.90–77.16% in cases, and 3.52–7.86% in controls, (p ≤ 0.001). SHOX2 methylation levels in comparison to tissue biopsy pathology (the gold standard test) had 76.92% sensitivity, 70% specificity, 87% positive predictive value, and 53.8% negative predictive value in diagnosing lung cancer. Different methylation levels were noted in different lung pathologies, (p = 0.003), with the highest methylation levels in squamous cell carcinoma followed by adenocarcinoma and anaplastic carcinoma then lastly carcinoma in situ. Conclusions SHOX2 methylation levels could differentiate different varieties of lung cancer from benign lung lesions.

Anaplastic large cell lymphoma (ALCL) is a non-Hodgkin lymphoma of T-cell or null-cell lineage with variable cytomorphology. We report two rare ALCL cases with carcinomatous and sarcomatous patterns, respectively, in fine needle aspiration (FNA) cytology and histopathology. The first case was a 56-year-old man with enlarged left inguinal lymph node. FNA smears showed a malignant small round cell tumor with nuclear molding. In addition, there were large bi-nucleated and multinucleated cells with wreath-like arrangement of nuclei. ALCL and small cell (neuroendocrine) carcinoma were the possibilities considered. Immunocytochemical studies on FNA smears showed positive reaction for leukocyte common antigen (LCA) and negative results for cytokeratin (CK) and chromogranin. Histopathological examination of the lymph node showed features of ALCL with following immunohistochemical staining results: LCA+, CD30+, CD45RO+, CD20-, CD3+ (weak), and Alk1-. During review of sections, areas resembling a small cell anaplastic carcinoma were observed. The second case was a 24-year-old woman with right cervical lymphadenopathy. FNA smears showed an ALCL with highly atypical large cells including bi-nucleated and donut shaped cells, which were positive for CD30, EMA, and Alk-1 protein, and negative for CD20, CD3, and CK. Histopathological examination corroborated the cytodiagnosis of ALCL, and with positive immunohistochemical staining for CD30, EMA, Alk-1 protein+, BCL6+, and Ki67+ (40% cells) and negative results for CD20, CD10, CD3, CD5, CD15, BCl2, CD79a, and CD68. Sarcomatous components were noticed during review of cytologic and histopathological specimen. Awareness about these unusual cytomorphological patterns in ALCL may be of help in proper diagnosis of this neoplasm.

The aim is to review the features of 117 primary squamous cell carcinomas of thyroid which meet the histological criteria of the World Health Organization classification of endocrine tumours. The carcinomas occur in 83 women and 34 men (female to male ratio is 2.4 to 1) and with median age at presentation of 64. Half of these squamous cell carcinomas of thyroid were moderately differentiated. PAX-8 protein is a sensitive marker for confirming the thyroid origin of the carcinoma. The carcinoma is also positive for p63, p40, cytokeratins 5/6, 7,19 and negative for cytokeratins 20 and 10/13. P53 overexpression is common. The most important differential diagnosis is direct infiltration or metastatic involvement by squamous cell carcinoma from other organs. Limited mutation analysis revealed BRAF mutation in some squamous cell carcinomas of the thyroid. The genetic profile appears to be different from anaplastic thyroid carcinomas. Primary squamous cell carcinoma of thyroid had lymph node involvement in 59% and distant metastases in 26%. The median survival of the patients was 8 months. Curative surgery offers the best survival for the patients with the carcinoma. To conclude, primary squamous cell carcinoma of the thyroid gland has distinctive clinical, pathological and molecular profiles. It is important to recognize this unique variant of thyroid carcinoma for possible curative surgical resection and to do more genomic works on the entity to uncover the molecular pathogenesis.

Objective: To determine the clinical presentation and histopathological evaluation of patients undergoing thyroidectomies at tertiary care Hospital. Methodology: This cross-sectional study was done at department of general surgery of LUMHS/Jamshoro. Duration of the study was 1 year from October 2017 to September 2018. All the cases with a diagnosis of thyroid disorder and underwent thyroidectomy were selected and above 25 years of the age were included. All the surgeries were carried out by senior surgeons along with the cooperation of the ENT surgeons. After surgeries specimens of all the cases were sent to the diagnostic laboratory for the histological assessment. Data was collected via self-made proforma. Results: Of 58 patients majority i.e. 43.10% were found with age group of 35-44 years. Females found in the majority 63.80%. The swelling was noted among all of the cases, followed by pain, difficulty in swallowing, difficulty in breathing and others 8.62%, 10.34%, 20.68% and 25.68% respectively. Adenomatous goiter was the most common histopathological finding in 82.75% cases, papillary carcinoma was found 8.62%, follicular carcinoma was only in one case and anaplastic carcinoma was also in 1 case. Conclusion: Swelling, difficulty in swallowing and difficulty in breathing were the most common clinical features. Adenomatous goiter was the most common histological finding and papillary carcinoma was the commonest malignancy.

Galectin-3 is a beta-galactoside binding animal lectin, which is frequently associated with tumour progression and metastasis. In recent years, overexpression of Galectin-3 has been reported in various human cancers and more frequently in thyroid neoplasms. The aim of this study was to analyze the histomorphological characteristics of malignant thyroid neoplasms, subtype them according to the established classification system and to evaluate the expression of Galectin-3 immunostaining in papillary thyroid carcinoma. A total of 30 cases were included in the study, out of which 28 cases were papillary thyroid carcinoma and its variants and one case of medullary and anaplastic carcinoma. Majority of the papillary thyroid carcinoma cases were positive for Galectin 3 immunostaining (25/28 cases – 89%) in our study. We conclude that galectin-3 is consistently expressed in papillary carcinoma thyroid; however, there are few false-negative cases in this study and also other studies have reported Galectin 3 overexpression in non-papillary tumors. Hence, we cannot depend on Galectin 3 expression alone as a single diagnostic tool to detect papillary thyroid carcinoma.

Mucinous tumors account approximately for 15% of all primary ovarian epithelial neoplasms. Ovarian mucinous tumors with mural nodules are rare surface epithelial-stromal tumorswhich can be of three types, “sarcoma-like”, sarcoma or anaplastic carcinoma. Mural nodules of anaplastic carcinoma were first described in 1982 by Prat et al following which approximately fifty cases have been reported to date and in those cases, only one has been associated with benign mucinous tumors. The current case report is from a 50-year-oldpostmenopausal woman who presented to the gynecology outpatient department with complaints of abdominal pain and distension for the past five months. On histopathological examination, a diagnosis of Mucinous cystadenoma with focal atypia and mural nodule of anaplastic carcinoma was made and confirmed with immunohistochemistry.

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.

Riedel's thyroiditis is a rare inflammatory process which not only involves thyroid gland but also the surrounding vital structures. It may also be associated with various forms of systemic fibrotic disorders. The exact etiology is not known, but currently, the most favored view is that of a localized form of the systemic fibrotic process. We report a case of Riedel's thyroiditis in a male patient, highlighting diagnostic challenges and a rare presentation of hypocalcemia and mimicking thyroid lymphoma. Clinical knowledge of such a presentation of Riedel's thyroiditis would enhance our ability to make a speedy diagnosis. Apart from avoiding aggressive surgical intervention, awareness of such a clinical entity may avoid complications and hence morbidity. Our case also highlights the difficulty in histological diagnosis which is vital to rule out malignancy and avoiding any major surgical intervention fraught with complications. Although the patient had a poor tolerance to Tamoxifen and Rituximab, however, his response to high dose steroids is the currently accepted treatment of choice. This case adds to the sparse literature available on the cytological diagnosis of RT and highlights the diagnostic challenge due to suspicious radiology findings., Highlights • Riedel's thyroiditis, a rare form of chronic thyroiditis is associated with a fibrotic process involving the thyroid gland, leading to anatomical and physiological consequences. • Riedel's thyroiditis is part of the spectrum of IgG4-related systemic disorders (IgG4-RSD). • Clinicians should be aware of RT to differentiate this condition from other thyroid disorders, especially malignant lesions. • Thyroidectomy is indicated for patients with compressive symptoms, suspicion of malignancy and failure of medical management.

Introduction/Background* Mucinous ovarian tumours account for ~10% of primary ovarian neoplasia and a generally diagnosed at an early stage with relatively favourable oncological outcomes. However those possessing anaplastic carcinoma within mural nodules rarer still and carry with them a poor prognosis and lack of consensus regarding their optimal treatment regime. Whilst a great deal of research has been published focusing on their histopathological and immunohistochemical characteristics, there is limited evidence nor consensus regarding their ideal adjuvant treatment regimes. This study sought to combine cases from our unit with a meta-analysis of cases in the literature to provide insight into current treatment regimes and outcomes. Methodology A systematic review was conducted of the English language literature to identify articles published regarding outcomes and treatment modalities of patients having anaplastic carcinoma foci within mucinous ovarian tumours. References of these articles were reviewed to identify all possible cases in the literature. Where treatment regimes were not listed in the publications the contact author was reached for comment. These cases were then combined with 7 cases from our own institution for a multivariate and survival analysis. Result(s)* A total of 66 cases were identified in the literature. Average age 43.7 (median 40.5), range 15-74yo. 83% of patients underwent a total abdominal hysterectomy, 17% of patients did not under go a hysterectomy, with the remaining 2 cases having been done laparoscopically. 70% of patients underwent a BSO, the remainder a USO. 50% of cases were FIGO stage IA1 at the time of diagnosis, of these 16% died during follow up with 3 of those dying within 12 months of diagnosis. Conclusion* Anaplastic mural nodules arising on a background of mucinous ovarian carcinoma are associated with heterogenous outcomes when considering progression free survival and overall survival. Their treatment within the literature is highly variable, particularly regarding adjuvant therapy. Patients with improved overall survival and progression free survival were more likely to be lower stage and have a smaller adnexal mass at diagnosis.

Purpose: The purpose of the present study is to investigate the capability of the combination of Learning Vector Quantizer (LVQ) Νeural Νetworks (NNs) in the discrimination of benign from malignant thyroid lesions.Patients and Method: The study was performed on Liquid Based Cytology (LBC) specimens taken by FNA and stained by Papanikolaou technique. From the cytological images, using a custom image analysis system, certain features, describing the size, shape and texture of approximately 100 nuclei per case, have been extracted. These features were used to classify each individual nucleus by an LVQ NN. In the sequel, the nucleus classification results for each case were used to classify each individual case by a second cascaded LVQ NN. The cases were distributed according to the histological diagnosis as follows: 165 cases were classified as goiter, 2 as nodular hyperplasias, 61 as Hashimoto thyroiditis, 3 as non specific thyroiditis, 21 as adenomatoid nodules, 3 as oxyphic adenomas and 4 cases as follicular adenomas. Αdditionally, 62 cases of papilary carcinoma, 9 of medullary carcinoma, 2 of anaplastic carcinoma and 3 of follicular carcinoma, were included.The data of about 50% of the cases from each class, were used for the training of two LVQ classifiers and the remaining data were used to test their performance. The proposed system was used to discriminate into the individual cellular level and subsequently into the individual patient level, between benign from malignant nuclei or cases.Results: The application of the LVQ NNs system allows successful discrimination between benign and malignant cell nuclei and lesions (overall accuracy 94,1% and 100% respectively).Conclusions: The results indicate that the use of neural networks combined with image morphometry may offer useful information on the potential of malignancy of thyroid lesions and could improve the diagnostic accuracy of FNA of the thyroid gland, especially in cases of follicular neoplasms classified as suspicious for malignancy and in cases of oncocytic tumors.

Poorly differentiated thyroid carcinoma (PDTC) and anaplastic thyroid carcinoma (ATC) have been hypothesized to arise from well-differentiated thyroid carcinoma (WDTC) due to frequently reported synchronous and metachronous occurrence. Loss of normal p53 function has been implicated in this dedifferentiation process. The current case report presents a 60-year-old male with multiple neurofibromas who underwent total thyroidectomy due to multiple palpable thyroid nodules. Histopathological examination revealed three foci of predominantly papillary, but also follicular carcinoma growth pattern, and two lesions with histological features of insular and trabecular variant, with the larger one showing foci of anaplastic transition. Nuclear p53 protein accumulation, corresponding to mutant abnormally stabilized p53, was higher in more aggressive variants compared with WDTC. The somatic molecular events and downstream pathways of this dedifferentiation course have not been unraveled yet. The present case report demonstrated the simultaneous presence of three divergent histological subtypes in a single thyroid gland, with progressive enhancement of nuclear p53 protein expression, associated with mutant p53 protein, in the more aggressive variants. This is a rare case of progressive enhancement of mutant nuclear p53 protein expression in multifocal thyroid tumor areas consisting of WDTC, PDTC and ATC histological types, highlighting the possibility that WDTC can progress to PDTC and then ATC through an intricate procedure, involving loss of normal p53 function.

Despite two centuries of progress in its surgical and oncological management, ovarian cancer remains the most lethal of the gynaecological cancers, claiming the lives of nearly 185,000 women globally each year. Historically considered a single disease, there is growing recognition that ovarian cancer is in fact a spectrum of malignancies with distinct cellular origins, molecular driver pathways and clinicopathological features. Mucinous ovarian carcinoma (mOC) is a rare histological subtype that presents a particular challenge in accurate diagnosis and management. Frequently confused with metastatic deposits from extra-ovarian mucinous tumours, the true incidence of primary mOC is estimated to be between 3-5%. Typically affecting younger women, prognosis for late-stage disease is abysmal with a median survival of

We evaluated treatment outcomes of external beam radiation therapy (EBRT) for unresectable locally advanced thyroid cancer (LATC) with or without metastasis. We enrolled 11 LATC patients who underwent EBRT (median age: 76 (45–83) years, six males and five females). Eastern Cooperative Oncology Group performance statuses of 0 (n = 3), 1 (n = 1), 2 (n = 6), and 3 (n = 1) were observed. Histologic types included papillary carcinoma (n = 5), anaplastic carcinoma (n = 3), and squamous cell carcinoma (n = 3). The organs invaded by the tumor that caused it to be deemed unresectable were common carotid artery (n = 5), trachea (n = 4), aorta (n = 1) and larynx (n = 1). The median follow-up time was 6 months. One, seven, two, and one patient showed complete response (CR), partial response (PR), stable disease, and progressive disease, respectively. The rate of local CR+PR was 73%, moreover, 75% of patients achieved a &gt, 30% tumor size reduction within 6 months. The median local progression-free survival of patients with local CR+PR was 11.5 (4–68) months. The median overall survival was 6 (1–68) months. Grade 3 acute complications occurred in five (45%) patients. No patients had Grade 4 or 5 complications. In conclusion, EBRT reduced the tumor volume in 75% of LATC patients without inducing severe toxicity. This therapy should be considered as a treatment option for LATC.

Undifferentiated carcinoma metastatic to the bowel is uncommon in surgical pathology practice and might be confused with primary gastrointestinal carcinoma, melanoma, lymphoma, and others. We present 14 cases of uni- (n = 9) or multifocal (n = 5) undifferentiated large cell/rhabdoid carcinoma presenting in the bowel of patients with concurrent (n = 9) or recent (diagnosed 1 to 25 months earlier; median, 4) non-small cell lung cancer (NSCLC). Patients were 6 females and 8 males, aged 52 to 85 years. Primary NSCLC was verified histologically in 10 cases and by imaging in 4. The undifferentiated histology was present in the lung biopsy in 4/10 patients (as sole pattern in 3 and combined with adenocarcinoma in 1) and was limited to the intestinal metastases in the remainder. PDL1 was strongly expressed in 7/9 cases (CPS: 41 to 100). Loss of at least one SWI/SNF subunit was detected in 7/13 cases (54%). SMARCA2 loss (n = 6) was most frequent and was combined with SMARCA4 loss in one case. PBRM1 loss was observed in one tumor. Successful molecular testing of 11 cases revealed BRAF mutations in 4 (3 were non-V600E variants), KRAS mutations in 3, and wildtype in 4. None had EGFR mutations. Analysis of 4 paired samples revealed concordant KRAS (2) and BRAF (1) mutations or wildtype (1). Our study indicates that undifferentiated carcinoma within the intestines of patients with concurrent/recent NSCLC represents dedifferentiated metastasis from the NSCLC. Recognition of this unusual presentation is cardinal to avoid misdiagnosis with inappropriate therapeutic and prognostic implications.

Anaplastic thyroid carcinoma (ATC) is a highly aggressive tumor and constitutes 2%–5% of all thyroid carcinomas. The cytological diagnosis of osteoclast giant cell variant of ATC is extremely rare, and only a few cases have been described in literature. A 67 - year-old female underwent fine-needle aspiration cytology from the thyroid nodule. Smears revealed hypercellular aspirate comprising of clusters and singly scattered atypical cells with few interspersed multinucleated tumor cells. Cytomorphological differential diagnosis of giant cell/pleomorphic variant of medullary carcinoma and anaplastic carcinoma was offered. Histomorphological features on cell block assisted with immunohistochemistry confirmed the diagnosis of ATC with osteoclastic-like giant cells. Computed tomography-guided right lung lesion aspirate was reported as metastasis of high-grade poorly differentiated carcinoma. The patient was managed with cisplatin-based chemotherapy. This case highlights the importance of cytological diagnosis of ATC to guide the treatment modality of chemotherapy thus avoiding surgery, especially in old moribund patient with lung metastasis.

Anaplastic carcinoma of the pancreas is rarely encountered and usually reported as case reports in the literature. Anaplastic carcinoma is prognosed worse than ductal adenocarcinomas of the pancreas. The effectiveness of chemotherapy and radiotherapy is controversial in the treatment progress. Basic treatment is curative surgery. We aimed to present the management of a case with pancreatic anaplastic carcinoma in which a mass detected at the head of the pancreas and was performed “Whipple” procedure.

Most pathologists are unaware that thyroid gland also produces mucin; often associated with typical thyroid carcinoma rather than primary mucinous neoplasm. We report an unusual case of anaplastic carcinoma of thyroid presenting with abundant extracellular mucin. A 65 year old lady presented with painless, neck swelling since 7-8 months. Thyroid function tests were within normal limits. Imaging suggested neoplastic aetiology of thyroid. Cytology revealed abundant extracellular mucin with occasional large atypical cells. Hence, metastasis followed by primary mucinous thyroid carcinoma was considered. After excluding secondary neoplasms, total thyroidectomy with lymphadenectomy was performed. Histopathology revealed an infiltrative tumour with abundant mucin & necrosis amidst fibrotic bands. Tumour cells were arranged in sheets, with features of anaplasia. Focus of papillary thyroid carcinoma also identified. Mucicarmine and Alcian blue special stains were positive. Immunohistochemistry results of positive cytokeratin and negative TTF1, thyroglobulin and calcitonin confirmed our results.

Osteoclast-like giant cell-type (OCGC) anaplastic carcinoma is a rare variant of pancreatic ductal adenocarcinoma, and its imaging characteristics and progression pattern have not been fully clarified. The patient was a 73-year-old man who had been incidentally found to have a pancreatic head tumor. Computed tomography demonstrated a 3-cm marginally enhanced mass at the pancreatic head, continuing toward the duodenum. Diffusion-weighted magnetic resonance imaging showed a retained diffusion capacity. Duodenoscopy revealed a 1.5-cm polypoid lesion, covered by a dirty coat, near the major papilla. Surgical material revealed OCGC pancreatic anaplastic carcinoma protruding to the duodenum, accompanied by multiple hemorrhagic foci and hemosiderin precipitations.

Background Mammary fibroadenomas are one of the most common tumors of female companion rats (Rattus norvegicus forma domestica). The objectives of this study were to determine if subcutaneous administration of a deslorelin implant following excision of fibroadenomas can prevent or delay development of additional mammary tumors and increase survival in companion rats. Methods Female intact client-owned rats with benign mammary tumors were divided into three groups: no implant (n = 10), placebo implant (n = 10), or 4.7 mg deslorelin implant (n = 10) placed within 2 months of tumor excision. Rats were monitored for subsequent mammary tumors for 10 months following treatment. Expression of estrogen α, progesterone, prolactin, and androgen receptors stained by immunohistochemistry in primary masses of rats included in the deslorelin-treated group was evaluated using the Allred scoring system. Results In the control non-implanted group, four of the 10 rats developed another mammary tumor, including one anaplastic carcinoma. In the control placebo group, five of the 10 rats developed another mammary tumor, including one ductal carcinoma. In the deslorelin-treated group, three of 10 rats developed another mammary tumor, including one adenocarcinoma. Median time between surgery and new mass detection did not differ significantly among groups (55 days in the deslorelin group vs. 77 days in the control placebo group, P = 0.25). Median survival times after surgery did not differ significantly among groups. No correlation was noted between receptor expression and response to treatment with deslorelin. Conclusions and clinical relevance Deslorelin implants placed within 2 months of benign mammary tumor surgical excision were not associated with a decreased risk of developing subsequent mammary tumors, nor with an increased survival in female rats. Further studies are needed to define useful adjunct therapy to surgery.

Background Anaplastic thyroid carcinomas are associated with rapid tumor growth, short survival time and without any promising therapy to improve the poor prognosis. In this study, expression of immunoregulative receptor CD1d and lymphocyte infiltration in different thyroid tumors as well as in healthy tissue were analyzed in order to find new targets for an immunotherapeutic approach. Methods CD1d immunohistochemistry was performed in samples of 18 anaplastic, 17 follicular, 27 papillary, and 4 medullary thyroid carcinomas as well as in 19 specimens from normal thyroid tissue and additionally in 10 samples of sarcoma, seven malignant melanoma and three spindle‐cell lung carcinoma. Furthermore, thyroid samples were stained with antibodies against CD3, CD20, CD56, CD68, and LCA in order to analyze lymphocyte infiltration. Results For the first time CD1d receptor expression on normal thyroid tissue could be demonstrated. Moreover, anaplastic thyroid carcinomas showed significantly higher expression levels compared to other thyroid samples. Most astonishingly, CD1d expression disappeared from the cellular surface and was detected rather in the cytoplasm of anaplastic thyroid carcinoma cells. In addition, histologically similar tumors to anaplastic carcinoma like sarcoma and malignant melanoma revealed distinct CD1d staining patterns. Furthermore, infiltration of T cells, B cells, and macrophages in anaplastic thyroid carcinomas was different when compared to normal thyroid tissue and all other thyroid carcinomas. Conclusions Anaplastic thyroid carcinomas show significantly higher expression of CD1d, a receptor for NKT cells, which are subject of several anticancer therapy studies. These results may offer a novel approach to explore immunotherapeutic treatment options., Anaplastic thyroid carcinomas show significantly higher expression of CD1d, a receptor for NKT cells, which are subject of several anticancer therapy studies. For anaplastic thyroid carcinomas, this may offer a new differentiation marker as well as a novel approach to explore immunotherapeutic treatment options.

A variety of soft tissue and visceral neoplasms have been associated with constitutional symptoms and signs including fever, fatigue, arthritis and laboratory abnormalities such as elevated erythrocyte sedimentation rate, leukocytosis with marked neutrophilia, anemia, thrombocytosis and others. This review addresses three main neoplastic categories that are associated with specific paraneoplastic phenomena: (1) neoplasms having in common the presence of diffuse mixed inflammatory infiltration (closely simulating an inflammatory pseudotumor) and frequently associated with constitutional symptoms; (2) neoplasms with undifferentiated, anaplastic or rhabdoid cell morphology (frequently SWI/SNF-deficient) associated with diverse paraneoplastic manifestations; and (3) paraneoplasia associated with neoplasms carrying specific gene fusions such as solitary fibrous tumor (STAT6-NAB2 gene fusions), infantile fibrosarcoma and congenital mesoblastic nephroma (ETV6-NTRK3 gene fusions), and angiomatoid fibrous histiocytoma (EWSR1-CREB1 & EWSR1-ATF1 fusions).

Anaplastic carcinoma of the pancreas (ACP) is a rare and aggressive variant of pancreatic ductal adenocarcinoma (PDAC). Several studies have attempted to characterize this subtype through case series or single case reports; however, ACP remains underrecognized by cytopathologists in particular, and often lumped under the umbrella of classic PDAC. Here, we review the most up to date data that literature provides about ACP, to bring familiarity with this entity to the cytopathology practice, and to elucidate the role cytopathologists can play in recognizing and diagnosing this subtype on pancreatic aspiration biopsy, before surgical resection. We also describe a rare case of ACP, demonstrating signet ring cell features, that was diagnosed on fine needle aspiration of a pancreatic mass.

Certain carcinomas of the thyroid gland behave aggressively resulting in increased patient morbidity and poor patient prognosis. The diagnosis of these aggressive thyroid cancer subtypes is sometimes challenging and subject to increased interobserver variability. This review deals with the cytological features of such tumors including aggressive variants of papillary thyroid carcinoma, poorly differentiated thyroid carcinoma, and anaplastic thyroid carcinoma. These malignancies fall into 2 groups based on their cytomorphology: those that exhibit distinct microscopic features (eg, nuclear findings typical of classical papillary thyroid carcinoma or marked anaplasia) and those that present with more subtle cytologic features (eg, nuclear pseudostratification, “soap bubble” nuclei, supranuclear or subnuclear cytoplasmic vacuoles, rosette-like structures, hobnail cells). We review the literature regarding these aggressive thyroid cancers and highlight important phenotypic characteristics that can be useful for their diagnosis based on fine needle aspiration.

Introduction:Exocrine pancreatic cancers include common type pancreatic ductal adenocarcinoma and cystic neoplasms, which account for 85% and 10% of cases, respectively. The remaining 5% are rare histotypes, comprising adenosquamous carcinoma, acinar cell carcinoma, signet ring cell carcinoma, medullary carcinoma, pancreatoblastoma, hepatoid carcinoma, undifferentiated carcinoma and its variant with osteoclast-like giant cells, solid pseudopapillary carcinoma, and carcinosarcoma. Due to their low incidence, little knowledge is available on their clinical and molecular features as well as on treatment choices. The national initiative presented here aims at the molecular characterization of series of rare histotypes for which therapeutic and follow-up data are available.Methods:A nationwide Italian Rare Pancreatic Cancer (IRaPaCa) task force whose first initiative is a multicentric retrospective study involving 21 Italian cancer centers to retrieve histologic material and clinical and treatment data of at least 100 patients with rare exocrine pancreatic cancers has been created. After histologic revision by a panel of expert pathologists, DNA and RNA from paraffin tissues will be investigated by next-generation sequencing using molecular pathway–oriented and immune-oriented mutational and expression profiling panels constructed availing of the information from the International Cancer Genome Consortium. Bioinformatic analysis of data will drive validation studies by immunohistochemistry and in situ hybridization, as well as nanostring assays.Conclusions:We expect to gather novel data on rare pancreatic cancer types that will be useful to inform the design of therapeutic choices.

Objective: The incidence of thyroid cancer has been continuously increasing. The main objective of this study was to investigate irisin expression in various thyroid pathologies and to compare these expression patterns with irisin expression in healthy thyroid tissues. Methods: The study groups consisted of 20 cases each of control thyroid tissue, Hashimoto’s thyroiditis, thyroid papillary carcinoma, oncocytic papillary carcinoma, follicular thyroid carcinoma, oncocytic follicular thyroid carcinoma, medullary thyroid carcinoma, anaplastic thyroid carcinoma. Irisin expression was evaluated using immunohistochemistry. Irisin levels in thyroid tissue supernatants were measured using ELISA. Results: Patients with HT showed increased irisin expression compared with controls (p

Background: Percutaneous, image-guided transthoracic fine needle aspiration cytology (TTFNAC) is a rapid, yet accurate, and well-established diagnostic method used in the cytological evaluation of intrathoracic lesions. The study was done to determine the utility of image-guided TTFNAC in diagnosis of intrathoracic lesions. Subjects and Methods: A retrospective analysis of all cases who underwent image-guided TTFNAC of a suspected intrathoracic lesion, in a tertiary care hospital was done over a period of 3 years. Results: During the study period, 124 cases of image-guided FNAC of intrathoracic lesions were obtained. The mean age at presentation was 60.5 years with M:F: 3.6:1. Neoplastic lesions (71.5%) outnumbered the nonneoplastic lesions (28.5%). The most common tumor was adenocarcinoma (25%) followed by squamous cell carcinoma (SCC, 11%), and small cell carcinoma (5%). There was one case each of anaplastic carcinoma, plasmacytoma, bronchoalveolar carcinoma, and non-Hodgkin lymphoma (NHL). Most of the lesions were found on the right side and upper lobe. Among the mediastinal lesions, we found two cases of thymoma and one case each of NHL)/primitive neuroectodermal tumor (PNET), NHL, and small cell carcinoma metastasis to lymph node followed by ten cases of inflammatory lesions and seven cases of tuberculosis (TB). Conclusion: Image-guided TTFNAC of intrathoracic lesions is a safe method when done by well-trained medical personnel with lesser rate of complications. An early accurate diagnosis of malignancy can be made based on the cytological features; however, further subtyping of the malignancy may sometimes be difficult due to overlapping cytological features. TTFNAC can be a diagnostic tool for identifying nonneoplastic lesion such as TB. Hence, image-guided FNAC aids in early diagnosis and management of patients with intrathoracic lesions.

Highlights • Malignant mural nodules in borderline ovarian tumors are rare and anaplastic mural nodules are still infrequent. • These aggressive tumors portend poor prognosis and carries high morbidity/mortality. • Stage ≥1C patients survive badly. Albeit, histological pattern of anaplastic nodules and stage/prognosis are not related. • Our patient, a postmenopausal lady had borderline ovarian mucinous tumor with an anaplastic carcinomatous mural nodule. • After comprehensive staging laparotomy and 6cycles of paclitaxel–carboplatin, she is clinically well at 8 m of follow up., Malignant mural nodules in borderline ovarian tumors are rare. Among them, anaplastic mural nodules are infrequent and only limited case reports are available. Here we report a patient diagnosed as borderline ovarian mucinous tumor with an anaplastic carcinomatous mural nodule. She underwent comprehensive staging laparotomy and six cycles of adjuvant chemotherapy with paclitaxel – carboplatin and has no evidence of disease progression at eight months of follow up. This tumor has an aggressive behaviour and patients with stage ≥1C have inferior survival.

Background Anaplastic thyroid carcinoma is a highly lethal subtype of thyroid cancer without effective therapies. Drug resistance in anaplastic thyroid carcinoma poses a significant problem. Although artemisinin exerts antitumor effects, but its efficacy in anaplastic thyroid carcinoma is unknown. Methods We used RNA sequencing to identify differentially expressed genes. Next, we determined the cause of ART resistance by testing the expression and activity of β-catenin, and enhanced ART activity with a WNT signaling inhibitor. Results Artemisinin suppressed the growth of BHT-101 but not human thyroid anaplastic carcinoma (CAL-62) cells. The mechanism of artemisinin resistance in CAL-62 was associated with the aberrant activation of WNT signaling. Pyrvinium pamoate, an inhibitor of WNT signaling, was used to overcome ART resistance in CAL-62 cells. The combination of artemisinin and pyrvinium pamoate suppressed the growth of CAL-62 cells and induced the apoptosis. Conclusions Our study is the first to prove the efficacy of ART as monotherapy or in combination with PP in the management of anaplastic thyroid cancer, and that the inhibition of WNT signaling may overcome ART resistance.