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Anaplastic thyroid carcinoma (ATC) with retrosternal extension is a very uncommon and extremely aggressive malignancy with an exceptionally poor prognosis. This cancer usually infiltrates the surrounding anatomic structures as well as metastasizes into the neck or upper mediastinal lymph nodes. Multimodal treatment including surgery, chemo-radiotherapy, and targeted and immunotherapies serves for the cure, ameliorates the symptoms, or prolongs the survival. Radical surgery remains the most effective treatment modality, but unfortunately, it is not always applicable. Neoadjuvant therapies may render the tumor into an operable one and give a real chance for healing. In this article, we report a case of a 75-year-old man with loco-regional advanced anaplastic (undifferentiated) high-grade thyroid carcinoma mixed with papillary carcinoma. It was performed a cervicotomy, proximal partial median sternotomy, total thyroidectomy, partial resection of the right prethyroid and sternocleidomastoid muscles, medial part of the right clavicle, upper right corner of manubrium, right sternoclavicular joint, right internal jugular vein, right vagal and phrenic nerves, partial resection of the right subclavian vein, and patch plasty of the latter with pericardium, pericardial fenestration. The patient was referred to adjuvant radiotherapy. [ABSTRACT FROM AUTHOR]

Background: Granulocyte colony-stimulating factor (G-CSF)-producing tumors have been reported in various organs, and the prognosis of patients with G-CSF-producing pancreatic cancers is particularly dismal. In this report, we present a case of G-CSF-producing anaplastic carcinoma of the pancreas (ACP), characterized by early postoperative recurrence and rapid, uncontrolled growth. Case presentation: A 74-year-old man presented to our hospital with complaints of abdominal fullness and pain after eating. On admission, it was observed that the peripheral leukocyte counts and serum G-CSF levels were significantly elevated (23,770/µL and 251 pg/mL, respectively). Computed tomography of the abdomen revealed a pancreatic head tumor involving the superior mesenteric vein. Pathologically, ultrasound-guided fine-needle aspiration confirmed ACP. Subsequently, we performed a subtotal stomach-preserving pancreaticoduodenectomy with portal vein reconstruction and partial transverse colon resection. On postoperative day (POD) 7, the leukocyte count decreased from 21,180/μL to 8490/μL; moreover, computed tomography revealed liver metastasis. Therefore, mFOLFILINOX chemotherapy was initiated on POD 30. However, the tumor exhibited rapid progression, and the patient died on POD 45. Conclusions: G-CSF-producing ACP is rare, and the prognosis of patients is extremely poor. Basic research is required to develop effective drugs against G-CSF-producing tumors, and large-scale studies using national databases are needed to develop multidisciplinary treatment methods. [ABSTRACT FROM AUTHOR]

Background: The density of tumor-associated macrophages in the tumor microenvironment of anaplastic thyroid cancer (ATC) is associated with poor prognosis. However, the crosstalk between macrophages and ATC cells is poorly understood. This study aimed to examine the impact of macrophages on cancer cell phenotypes. We found a new mediator between M2 macrophages and ATC cells through proteomics analysis. Methods: The role of macrophages in proliferation, migration, and invasion of ATC cells was evaluated using coculture assay and conditioned medium (CM). Secretory factors in the CM from single or coculture were identified using liquid chromatography-tandem mass spectrometry proteomics analysis. We evaluated the role of the secretory factor in proliferation, migration, and invasion of cancer cells. In vivo xenograft model was used to evaluate the effect of the factor. Results: M2 macrophages significantly increased the proliferation, migration, and invasion of ATC cells, whereas M1 macrophages decreased the proliferation, migration, and invasion of ATC cells. Based on proteomic analysis of CM, we identify carboxypeptidase A4 (CPA4) as a mediator of the crosstalk between macrophages and ATC cells. CPA4 was only detected in the coculture media of M2 macrophage/8505C, and its expression in cancer cells increased by M2 macrophage. The expression of CPA4 protein was significantly higher in human thyroid cancers, particularly in ATCs, than normal and benign tissues. A bioinformatics analysis of public data revealed that CPA4 expression was associated with poor prognosis and dedifferentiation of thyroid cancer. Knockdown of CPA4 suppressed proliferation, colony formation, migration, and invasion of ATC cells, consistent with the decrease of STAT3, ERK, and AKT/mTOR phosphorylation and epithelial-mesenchymal transition (EMT) marker expression. In addition, the increased expression of CPA4 in cancer cells by M2 macrophage stimulation induced the polarization of macrophages to the M2 phenotype, which formed a positive feedback loop. Xenograft tumors did not develop after CPA4 knockdown. Conclusions: Our data suggest that CPA4 stimulates the progression of thyroid cancer by mediating between M2 macrophages and ATC cells. CPA4 can be a new therapeutic target for the treatment of patients with ATC. [ABSTRACT FROM AUTHOR]

Background: In Sudan, there is limited knowledge on the epidemiology, clinical characteristics and pathological patterns of thyroid cancer. To address this shortcoming, we studied the clinical, pathological and treatment patterns of thyroid cancer at the National Cancer Institute ‒ University of Gezira (NCI-UG), Sudan. Methods: We performed a retrospective health facility–based study of patients with thyroid cancer who were treated at NCI–UG from January 2009 to December 2017. Results: A total of 139 patients with thyroid cancer were identified during the study period. Tumors were more common among women (69%). Goiter was the main presenting symptom (85%). The most common type of thyroid cancer was follicular carcinoma (41%), followed by papillary carcinoma (24%), then anaplastic carcinoma (20%). The mean age of the women was 56.3 years (SD ± 14.7), compared to 52.5 years (SD ± 16.6) for the men. The frequencies of stage I, II, III, and IV were 17%, 22%, 16%, and 45%, respectively. Different types of thyroidectomies were performed in 79% of the cases, lobectomy in 4%, and no surgery in 17%. Only 28% of the cases received radioactive iodine. Palliative chemotherapy and radiotherapy were prescribed to 17% and 37% of the cases, respectively. Conclusion: Thyroid cancer is more prevalent among women and most patients present at later stages. The dominance of follicular type suggests that the majority of this population is iodine-deficient. [ABSTRACT FROM AUTHOR]

Simple Summary: Differential diagnosis by optical microscopy on biopsies of low-incidence tumors of the same organ can be difficult, hampering patient management, particularly in the many places around the world lacking advanced facilities for cancer diagnosis beyond a histopathology laboratory. Examples of these tumors are the Hurthle cell, anaplastic, and medullary carcinomas of the thyroid. Currently, there are no specific biomarkers detectable by optical microscopy for any of them. We study the Chaperone System of these tumors by immunohistochemistry to determine if its components show distinctive levels and distribution patterns. Here we report that the molecular chaperones Hsp27, Hsp60, and Hsp90, show quantitative levels and distribution patterns different for each tumor and different from those of a benign thyroid pathology, goiter. Therefore, the reported methodology offers a promising tool to diagnose these three malignancies, and for revealing clues about the role of the three chaperones in carcinogenesis of thyroid tissue. Hurthle cell (HC), anaplastic (AC), and medullary (MC) carcinomas are low frequency thyroid tumors that pose several challenges for physicians and pathologists due to the scarcity of cases, information, and histopathological images, especially in the many areas around the world in which sophisticated molecular and genetic diagnostic facilities are unavailable. It is, therefore, cogent to provide tools for microscopists to achieve accurate diagnosis, such as histopathological images with reliable biomarkers, which can help them to reach a differential diagnosis. We are investigating whether components of the chaperone system (CS), such as the molecular chaperones, can be considered dependable biomarkers, whose levels and distribution inside and outside cells in the tumor tissue could present a distinctive histopathological pattern for each tumor type. Here, we report data on the chaperones Hsp27, Hsp60, and Hsp90. They presented quantitative levels and distribution patterns that were different for each tumor and differed from those of a benign thyroid pathology, goiter (BG). Therefore, the reported methodology can be beneficial when the microscopist must differentiate between HC, AC, MC, and BG. [ABSTRACT FROM AUTHOR]

Anaplastic thyroid carcinoma (ATC) is a rare thyroid malignancy with a dire prognosis, nearly 100% disease specific mortality and a median overall survival less than 6 months. In view of the limited data from India on anaplastic thyroid cancer, we conducted this audit to analyze the treatment pattern, outcomes and factors influencing it. This is a retrospective analysis of outcomes of patients treated in a single institution between January 2008 and December 2020. Baseline characteristics, treatment received, and outcomes among adult patients with ATC were collected. Progression free survival (PFS) and overall survival (OS) were analyzed. SPSS version 20 and RStudio version 3.1.1 were used for analysis. In this cohort of 134 patients, the median age at diagnosis was 59 years, with 63.4% of them being females. At presentation, 70.9% of them had good performance status (PS 0–1). Only 38.8% received treatment with curative intent (either surgery fb adjuvant or neoadjuvant chemotherapy fb surgery and adjuvant or definitive chemoradiotherapy) while 61.2% patients received palliative treatment (either palliation alone or palliative chemotherapy or palliative surgery or palliative RT). Predominant pattern of progression was local progression (79.8%). Median PFS and OS of the overall cohort were 58 days and 80 days respectively. PFS and OS were significantly better in patients treated with curative intent vs palliative intent (116 and 134 days vs 45 and 50 days; p = 0.00 and 0.00 respectively). Among patients treated with curative intent, OS was significantly better in patients undergoing surgery vs CTRT (155 vs 76 days; p = 0.03). Among patients treated with upfront surgery, both PFS and OS were better with the addition of adjuvant CTRT/RT vs no adjuvant (332 and 540 days vs 55 and 91 days; p = 0.00 and 0.003 respectively). ATC is a rare cancer with dismal prognosis. Local therapy with surgery followed adjuvant seems to be associated with the better outcomes. Systemic therapy seems to be a better option for palliation. Our data reflects the real world data of this rare cancer. [ABSTRACT FROM AUTHOR]

Purpose: The incidence of thyroid carcinoma has increased globally in the past years. Papillary thyroid carcinoma (PTC) is the most frequent neoplasm of the thyroid gland comprehending the 90% of the thyroid carcinoma and has an indolent clinical behaviour. However, some variants of follicular cell-derived thyroid carcinoma, including variants of classic of PTC, have been identified that show a more aggressive biological behaviour. An accurate diagnosis of these entities is crucial for planning a more aggressive treatment and improving patients' prognosis of patients. The aim of this review is to present the main clinical, histological, and molecular features of aggressive variants of follicular cell-derived thyroid carcinoma, and to provide useful histological parameters for determining the most suitable therapeutic strategy for patients affected by these forms. Results: Variants of classic PTC such as the diffuse sclerosing variant (DSV), the tall cell variant (TCV), the columnar cell variant (CCV), the solid/trabecular variant (STV) and the hobnail variant (HV), and other variants of follicular cell-derived thyroid carcinoma, such as poorly differentiated thyroid carcinoma (PDTC), and anaplastic thyroid carcinoma (ATC), are associated with aggressive behaviour. Conclusions: The correct identification and diagnosis of aggressive variants of follicular cell-derived thyroid carcinoma is important, as they allow the clinician to adopt the most refined therapeutic strategies in order to the survival of the patients. [ABSTRACT FROM AUTHOR]

Dabrafenib is a BRAF kinase inhibitor approved for treatment of BRAF-mutated anaplastic thyroid carcinoma (ATC) in combination with trametin ib. Erlotinib is a tyrosine kinase inhibitor of EGF receptor (EGFR). We evaluated effects of dabrafenib and erlotinib combination treatment on ATC cells in vitro and in vivo. Cell proliferation, colony formation, apoptosis, and migration of ATC cells harbori ng a BRAF mutation (BHT101, 8505C, and SW1736) were evaluated after treatment with dabrafenib in combination with erlotinib or trametinib. The changes in act ivation of mitogen extracellular kinase (MEK) and extracellular signal-related kin ase (ERK) signaling were also evaluated by Western blot analysis. Effects of these c ombinations were also evaluated using an in vivo xenograft model. First, we detected EGFR activation in dabrafenib-resistant SW1736 cells using a phospho-receptor tyro sine kinase array. A dabrafenib and erlotinib combination synergistically inhibite d cell proliferation, colony formation, and migration, with an induction of apoptotic cell death in all three ATC cells, compared with dabrafenib or erlotinib alone. This synergistic effect was comparable with a dabrafenib and trametinib combination. The dabrafenib and erlotinib combination effectively inhibited phosphorylated (p)-M EK, p-ERK, and p-EGFR expressions compared with dabrafenib or erlotinib alone, while the dabrafenib and trametinib combination only inhibited p-MEK and p-ERK expressio ns. The dabrafenib with erlotinib or trametinib combinations also significantly sup pressed tumor growth and induced apoptosis in a BHT101 xenograft model. The dabrafen ib and erlotinib combination could be a potential novel treatment regimen to ove rcome drug resistance to dabrafenib alone in patients with BRAF-mutated ATC. [ABSTRACT FROM AUTHOR]

Osteoclast‐like giant cell–rich variant of anaplastic thyroid carcinoma is extremely uncommon. In this paper we describe one such case in a 50 year‐old male. The patient presented with enlarged cervical lymph node after initial total thyroidectomy. The fine needle aspiration cytology (FNAC) smear showed abundant multinucleated osteoclastic‐like giant cells and scattered large bizarre tumour cells. FNAC of such cases may often be mistaken as osteoclast‐like giant cell–rich lesions. [ABSTRACT FROM AUTHOR]

Background: Anaplastic thyroid carcinoma is a rare, rapidly progressive, and highly aggressive tumor. It has a global annual incidence of 1-2 per million people. It mostly affects older adults and women. The median survival duration after diagnosis does not exceed 6-8 months.Case Presentation: A 60-year-old female patient of mixed race (Honduran) presented to the local medical service with dysphonia that had started approximately 2 months earlier, accompanied by orthopnea that had started 1 month earlier. On physical examination, a soft mass was palpated within the anterior neck region; it was approximately 4 cm in diameter, painless, and mobile on swallowing, and had irregular margins. Ultrasound and computed tomography of the neck were performed. Subsequently, fine needle aspiration biopsy was performed. The histological diagnosis was anaplastic thyroid carcinoma (stage IVB). She underwent total thyroidectomy and chemotherapy. She is currently in her fifth year of remission after diagnosis and remains under oncologic surveillance.Discussion: Anaplastic thyroid carcinoma demonstrates a lethal behavior. Approximately 18% survive for more than a year after diagnosis, and 0-10% survive for 5 years. Different pretherapeutic prognostic factors may affect survival, including age < 70 years, the absence of distant metastases, and complete local resection.Conclusion: Conventional treatment improves the quality of life of the patient, but the results are not encouraging for the medium and long term. Only a few patients manage to exceed the average life expectancy of 3-6 months, despite undergoing the currently available therapeutic regimen. [ABSTRACT FROM AUTHOR]

Extramammary Paget disease (EMPD) is a rare cutaneous malignancy that typically involves the genital skin and can be primary or associated with an underlying internal malignancy. The typical histopathological appearance of EMPD consists of single or small aggregates of cells with abundant pale cytoplasm and large pleomorphic nuclei, known as Paget cells, scattered throughout the epidermis. We report a case of anogenital EMPD occurring in a 53‐year‐old man with unusual histopathologic findings of marked epidermal acanthosis, acantholysis, intraepidermal glandular differentiation, and prominent plasma cell‐rich fibrovascular cores. These features were entirely confined to the epidermis and adnexa with no evidence of dermal invasion or underlying systemic disease. We review and summarize the literature for atypical features noted in EMPD and summarize similar findings previously described under a variety of descriptions including anaplastic EMPD, anogenital syringocystadenocarcinoma papilliferum in situ (SCACPIS), SCACPIS‐like changes in EMPD, and EMPD mimicking acantholytic squamous cell carcinoma in situ. We propose that these features represent a single entity and be considered under a unifying diagnosis to facilitate recognition of this entity. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. This study was conducted at 17 institutions in Japan, and a total of 55 patients were analyzed. 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 < 0.001). 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. [ABSTRACT FROM AUTHOR]

Anaplastic carcinoma (AC) is a rare but highly aggressive form of thyroid cancer. It mostly arises on a background of pre-existing well-differentiated cancer (WDC); however, whether it evolves directly from a WDC or originates as a second independent neoplasm is still to be defined. To obtain further insights into these mechanisms, we performed morphological, immunohistochemical, and next-generation sequencing analyses to compare AC and its associated WDC in a subset of 13 surgically resected specimens. Histologically, most WDC were of aggressive subtypes. Papillary carcinomas (8 cases; 62%) were tall cell (4/8), columnar (1/8), classic with hobnail features (1/8), classic and follicular variant in the remaining 2 cases; Hürthle cell and follicular carcinomas were present in 5 (38%) and in 1 (8%) patient, respectively. One patient harbored both a PTC, follicular variant, and a Hürthle cell carcinoma. We did not find any correlation between a histotype of WDC and a specific anaplastic growth pattern. Immunohistochemically, ACs retained pankeratin/PAX8 expression but with significantly lower levels than WDCs, and they tended to lose TTF1 expression, as can be expected within a dedifferentiation process. In addition, AC showed a more frequent expression of p63 and/or SMA, a mutated pattern of p53, and an abnormal expression of p16. Genetic analysis showed that the number of mutations was higher in AC than in the associated WDC, confirming a role of the progressive accumulation of genetic damage in this transition. We observed that mutations found in the WDCs were consistently identified in the anaplastic counterparts, further supporting the hypothesis of a developmental link. [ABSTRACT FROM AUTHOR]

Aims: Anaplastic carcinoma arising in a mucinous tumour of the ovary and rarely in the retroperitoneum is an uncommon neoplasm with three morphological patterns; rhabdoid, sarcomatoid and pleomorphic. We investigated expression of switch/sucrose non‐fermentable (SWI/SNF) chromatin remodelling complex components and claudin‐4 expression. Methods and results: Twenty‐two ovarian and three retroperitoneal mucinous tumours were investigated using antibodies against SMARCB1, SMARCA4, SMARCA2, ARID1A and claudin‐4. Loss of nuclear staining for any SWI/SNF protein was observed in the anaplastic component of nine of 25 (36%), with retained expression within the mucinous component of all tumours. Five (56%) showed loss of more than one protein, with dual loss of SMARCA4 and SMARCA2 in two, loss of SMARCA2 and ARID1A in two and loss of SMARCB1 and SMARCA2 in one. Retained expression of claudin‐4 was seen in 39% of the anaplastic carcinomas and within the mucinous component of all tumours. Rhabdoid morphology was associated with poor prognosis [stages III or IV disease (six of six, 100% versus four of 14, 29%; P = 0.0108] and death from disease (three of four, 75% versus one of 13, 8%; P = 0.0223). Although loss of a SWI/SNF protein was not significantly associated with death from disease (three of five, 60% versus one of 12, 8%; P = 0.0525), it showed a trend in correlation with poor prognosis and was often noted in tumours with rhabdoid morphology within this small cohort. Conclusions: Our report adds to the growing list of female genital tract malignancies with loss of SWI/SNF proteins, underlining their broad differential diagnosis and the importance of careful, context‐dependent interpretation of SWI/SNF protein loss. [ABSTRACT FROM AUTHOR]

Background: Anaplastic thyroid carcinoma (ATC) is a rare malignant tumor. In addition to the main ATC type with classical histopathological features, the other morphological types of ATC include paucicellular variant, angiomatoid, lymphoepithelioma-like, and small-cell variant. However, an ATC variant with a chondrosarcomatous component has not been reported to date. Case presentation: Computed tomography imaging of a 63-year-old male with a 2-month history of a cervical mass revealed a 4.5-cm lesion with heterogeneous enhancement in the left thyroid lobe and two smooth and homogeneous nodules in the right thyroid lobe. The patient underwent total thyroidectomy and cervical lymph node resection. Histologically, the tumor boundary in the left lobe was clear, with a few mitotically active, spindle sarcoma-like tumor cells observed in some areas. Immunohistochemically, these spindle cells were positive for vimentin and negative for cytokeratin, paired box-8, epithelial membrane antigen, calcitonin, thyroglobulin, and thyroid transcription factor-1. In other areas, abundant cartilage matrix production and irregularly shaped lobules of cartilage, often separated by fibrous bands, were observed. The chondrocytes appeared mildly/moderately atypical and contained enlarged, hyperchromatic nucleoli. One of the two nodules in the right thyroid lobe had a clear boundary and comprised some bland spindle cells in a prominently collagenous stroma with clear boundaries. The other nodule in the right thyroid lobe was completely enclosed within a thin, fibrous capsule and exhibited normofollicular and microfollicular architecture. The patient received adjuvant radiotherapy after the surgery and was free of any local or regional recurrence or distant metastases at the 8-month follow-up evaluation. Conclusions: This unusual case of ATC with chondrosarcomatous differentiation is an important addition to the morphology spectrum of ATC types. [ABSTRACT FROM AUTHOR]

Even in the 21st century, filariasis still remains one of the major health problems plaguing India. Filariasis usually presents as superficial swelling and lymphedema. It is uncommon for microfilaria to be seen during routine cytological examination. It is even rarer to find microfilaria coexisting with neoplastic lesions. Ninety-five percent of cases of lymphatic filariasis are caused by Wuchereria bancrofti and are rarely found in the thyroid gland. Here, we report a case of a 47-year-old male who presented with midline neck swelling, for which he underwent fine needle aspiration cytology which showed microfilaria coexisting with anaplastic carcinoma of the thyroid gland. [ABSTRACT FROM AUTHOR]

After being described in the salivary glands as a malignancy with features essentially identical to those of the breast, secretory carcinoma (SC) (formerly mammary analogue SC) has now been identified in other sites including the skin, lung, and thyroid gland. In the breast, SC has a relatively favorable prognosis. Likewise when arising in the salivary glands, it is generally considered to be a low to intermediate grade carcinoma; however, there is a range of clinical behavior with occasional patients dying of progressive disease. SCs of the thyroid gland are rare, and reports suggest a relatively aggressive behavior, at least relative to well differentiated carcinomas such as papillary carcinoma and minimally invasive follicular carcinoma. We present a patient with a highly aggressive thyroid gland SC that mimicked undifferentiated carcinoma clinically. The patient had widespread metastatic disease and died rapidly from airway compromise. We also review the literature for reported cases of thyroid gland SC in order to better establish the clinical features and expected clinical course of such tumors occurring at this site. [ABSTRACT FROM AUTHOR]

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. 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. We review the literature regarding these aggressive thyroid cancers and highlight important phenotypic characteristics that can be useful for their diagnosis via fine needle aspiration. [ABSTRACT FROM AUTHOR]

S100A4 (metastasin), a member of the S100 protein family, was initially identified in metastatic cells and is well established as a marker of aggressive human cancer. However, expression and roles of S100A4 in canine mammary tumors have not been clarified. In this study, expression of S100A4 was examined immunohistochemically in normal, hyperplastic, and neoplastic mammary glands of dogs. In all normal and benign lesions, S100A4 was restricted to a few stromal fibroblasts and inflammatory cells. However, in 7 of 57 (12%) of the malignant tumors examined, cytoplasmic and nuclear expression of S100A4 was observed in epithelial tumor cells and stromal cells. Particularly, the frequency of S100A4-positive anaplastic carcinomas was high (4/8 cases, 50%). Next, we established a novel cell line, named NV-CML, from a S100A4-positive canine mammary carcinoma. The cultured NV-CML cells and the tumors that developed in the immunodeficient mice after subcutaneous injection of the cells maintained the immunophenotype of the original tumor, including S100A4 expression. Using this cell line, we examined the cellular functions of S100A4 using RNA interference. S100A4 expression level in NV-CML cells transfected with small interfering RNA (siRNA) targeting canine S100A4 (siS100A4) was reduced to about one-fifth of those with negative-control siRNA (siNeg). Cell proliferation in WST-8 assay and cell migration in Boyden chamber assay were significantly decreased in siS100A4-transfected cells compared with siNeg-transfected cells. These findings suggest that S100A4 may be related to progression of canine mammary carcinomas via its influence on cell growth and motility. [ABSTRACT FROM AUTHOR]

Background: Thyroid cancer accounts for approximately 1% of total cancer cases. Thyroid neoplasms are most common malignant lesions in endocrine system. Their incidence is rapidly increasing in recent times, partially attributed to increased awareness and earlier detection of asymptomatic tumors. They present clinically as nodular or diffuse mass lesions of thyroid similar to non- neoplastic lesions. A wide spectrum of neoplasms is encountered and histopathology evaluation is crucial to establish diagnosis. This study is done to present spectrum of thyroid neoplasms with varied histomorphology at a tertiary care center. Aim: To study the spectrum of thyroid neoplasms at MNJ Institute of Oncology for over a period of one year with special mention of interesting cases and overview of diagnostic pitfalls encountered. Materials and methods: All thyroidectomy specimens submitted to Department of Pathology for a period of one year, from October 2017 to September 2018 were included in study. Routine processing and staining along with ancillary techniques where ever necessary were used to arrive at diagnosis. Results: A total of 104 thyroidectomy specimens were included in the present study. Thyroid cancer was common in females. The most commonly encountered malignancy was Papillary carcinoma, seen in 30-40 years age group. Anaplastic carcinoma was seen in 60-70 years age group. Conclusion: Papillary carcinoma was most commonly encountered thyroid malignancy followed by medullary and anaplastic carcinoma. Follicular adenoma was the most common benign neoplasm. We have encountered almost the entire spectrum of thyroid neoplasms including the rare variants. [ABSTRACT FROM AUTHOR]

Pseudomesotheliomatous carcinoma is a malignant tumor that extends along the pleura mimicking malignant mesothelioma. An 81‐year‐old male patient presented to our hospital with epigastralgia, and abdominal computed tomography (CT) showed a 36‐mm tumor in the pancreatic tail. The laboratory data revealed a high leukocyte count (>44 000/μL). Chest CT showed left pleural thickening with pleural effusion. The cancer showed a poor response to chemotherapy, and the patient died of respiratory failure at 5 months after the onset of disease. Autopsy showed solid tumor with hemorrhage, measuring 6 cm in diameter, in the pancreatic tail, with wide invasion to the stomach, left adrenal gland, spleen, and diaphragm. The left pleura, which was circumferentially thickened by the involved tumor, macroscopically resembled pleural mesothelioma. Histologically, the primary pancreatic tumor was diagnosed as anaplastic carcinoma, due to the absence of glandular structures or other features that would indicate a definite direction of differentiation. The primary lesion and carcinoma involving the left pleura were all positive for G‐CSF. We recently experienced an autopsy case of G‐CSF‐producing anaplastic carcinoma with pseudomesotheliomatous spread. [ABSTRACT FROM AUTHOR]

PD-L1 expression is being considered a potential biomarker for response of anti-PD-1 or anti-PD-L1 agents in various tumors. The reported frequency of PD-L1 positivity varies in thyroid carcinomas, and multiple factors may contribute to the variability in PD-L1 positivity. We evaluated the PD-L1 expression in various thyroid cancers on a large scale. A total of 407 primary thyroid cancers with a median 13.7-year of follow-up were included. We evaluated the frequency of PD-L1 expression using a rabbit monoclonal antibody (clone SP142). In addition, we analyzed the relationships between PD-L1 expression and clinicopathologic factors, including TERT promoter, BRAF status and disease progression. Tumoral PD-L1 was expressed in 6.1% of papillary thyroid carcinomas, 7.6% of follicular thyroid carcinomas and 22.2% of anaplastic thyroid carcinomas. The distribution of PD-L1 positivity was different according to cancer histology types (P < 0.001). All PD-L1-positive cases of follicular thyroid carcinoma and anaplastic thyroid carcinoma showed strong intensity. The proportions of positivity in PD-L1 positive anaplastic thyroid carcinomas were more than 80%. PD-L1 in immune cells was positive in 28.5% of papillary thyroid carcinoma, 9.1% of follicular thyroid carcinomas and 11.1% of anaplastic thyroid carcinomas. There was no significant association between clinicopathologic variables, disease progression, oncogenic mutation and PD-L1 expression. PD-L1 was highly expressed in a subset of patients with advanced thyroid cancer, such as follicular and anaplastic thyroid carcinoma. Identification of PD-L1 expression may have direct therapeutic relevance to patients with refractory thyroid cancer. [ABSTRACT FROM AUTHOR]

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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 most favored view is that of a localized form of systemic fibrotic process. We report a case of Riedel's thyroiditis in a patient, highlighting a rare presentation mimicking anaplastic carcinoma. Clinical awareness of such presentation of Riedel's thyroiditis would enhance our ability to make this diagnosis promptly. Apart from avoiding or minimizing aggressive surgical intervention, awareness of such clinical entity may avoid complications and hence morbidity. Our case also highlights the difficulty in histological diagnosis which is very important to rule out malignancy and avoiding any major surgical intervention fraught with complications. Good response to high dose steroids as seen in our case is the current accepted treatment of choice. [ABSTRACT FROM AUTHOR]

Anaplastic pancreatic carcinoma (ANPC) accounts for ~5% of all pancreatic ductal adenocarcinoma cases. Due to its rarity, its clinical features and surgical outcomes remain to be clearly understood. A 74-year-old woman was admitted to Onomichi General Hospital (Onomichi, Japan) in April 2015 without any significant past medical history. Contrast-enhanced computed tomography (CT) revealed a 9.5x8.0 cm tumor in the body and tail of the pancreas. The patient developed acute abdominal pain 3 weeks later and the CT revealed massive abdominal bleeding caused by tumor rupture. The tumor increased in size and reached 12.0x10.0 cm in maximal diameter. The tumor doubling time was estimated to be 13 days. 18F-fluorodeoxyglucose (FDG) positron emission tomography/CT confirmed the absence of distant metastasis since FDG accumulation was detected only in the tumor lesion. Emergency distal pancreatectomy and splenectomy were performed. Histologically, the tumor was classified as a spindle cell ANPC with rhabdoid features. The patient succumbed to mortality 8 months following the surgery while undergoing systemic adjuvant chemotherapy for multiple liver metastases. ANPC is difficult to detect in the early stages due to its progressive nature and atypical radiological findings. Long-term survival can be achieved only by curative resection; therefore, surgical resection must be performed whenever possible, even if the chance of long-term survival following surgery is considered dismal. As the present case suggested, spindle cell ANPC with rhabdoid features is highly aggressive and curative-intent resection must not be delayed. [ABSTRACT FROM AUTHOR]

Few reports of mucinous cystic neoplasm (MCN) in association with anaplastic carcinoma exist. The present study reported an unusual case of a 25-year-old female exhibiting large pancreatic MCN with anaplastic carcinoma. Notably, the patient was a Jehovah's Witness and therefore refused any blood transfusions. Preoperative diagnosis was invasive pancreatic MCN measuring 12.5 cm with ascites. Distal pancreatectomy was performed in combination with splenectomy and partial resection of the transverse colon. Intraoperative estimated blood loss was 400 ml, therefore a blood transfusion was not required. The patient had an uneventful postoperative course. The pathological diagnosis was mucinous cystadenocarcinoma of the pancreas with anaplastic carcinoma. Although the patient underwent postoperative adjuvant chemotherapy with gemcitabine and oral fluoropyrimidine (S-1), recurrence with peritoneal dissemination was detected 20 months following surgery and the patient succumbed to the recurrence 32 months following surgery. To the best of our knowledge, this is the first case report of MCN with anaplastic carcinoma of the pancreas in a Jehovah's Witness patient undergoing pancreatic surgery. [ABSTRACT FROM AUTHOR]

Primary thyroid lymphoma is a rare neoplasm consisting of 1%–5% of all thyroid neoplasms. These are predominantly B-cell in origin. It is curable without surgery. The literature search shows it to be presenting as rapidly developing thyroid mass. It has been shown to be associated with autoimmune thyroiditis. The rarity of this condition mandates it to be differentiated from other rapidly developing thyroid malignancies to recognize it early as it is curable. The treatment consists of chemotherapy, radiation, or both combined with excellent results. [ABSTRACT FROM AUTHOR]

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 most favored view is that of a localized form of systemic fibrotic process. We report a case of Riedel's thyroiditis in a patient, highlighting a rare presentation mimicking anaplastic carcinoma. Clinical awareness of such presentation of Riedel's thyroiditis would enhance our ability to make this diagnosis promptly. Apart from avoiding or minimizing aggressive surgical intervention, awareness of such clinical entity may avoid complications and hence morbidity. Our case also highlights the difficulty in histological diagnosis which is very important to rule out malignancy and avoiding any major surgical intervention fraught with complications. Good response to high dose steroids as seen in our case is the current accepted treatment of choice. [ABSTRACT FROM AUTHOR]

We herein report a case of anaplastic carcinoma of the pancreas arising in an intraductal papillary mucinous neoplasm (IPMN). A 68-year-old Japanese woman was admitted to our hospital complaining of fatigue. Computed tomography revealed an irregular mass in the pancreatic head, which displayed high-signal intensity on diffusion-weighted magnetic resonance imaging. Accordingly, the patient was diagnosed with pancreatic cancer and underwent pancreaticoduodenectomy. The histopathological findings revealed intraductal papillary proliferative changes involving the main and branch ducts of the pancreatic head. Based on the immunohistochemistry results, the intraductal lesion was diagnosed as IPMN. The pathological diagnosis for the invasive carcinoma was anaplastic giant-cell carcinoma of the pancreas (ACP), and the focus of IPMN dedifferentiation to ACP was found to be located at the periphery of the IPMN. At 18 months postoperatively, the patient remains disease-free. [ABSTRACT FROM AUTHOR]

Background: The prevalence and pathology pattern of iodine deficiency (ID) related disorders are influenced by the dietary iodine intake: low iodine leads to thyroid nodular enlargement, to an increase in the incidence of thyroid cancer, an increase in anaplastic carcinomas and to an alteration in the papillary to follicular neoplasia ratio. This study aims at highlighting the effects of ID by comparatively evaluating the pattern of thyroid nodular pathology in different populations that, although geographically distant and heterogeneous, both had iodine deficiency at the time of data gathering and are at high altitude: Beira Interior (BI) in Portugal and Johannesburg (JHB) in South Africa. (S.A.) Mandatory salt iodization introduced in S. A. in 1995 has recently been shown to have resulted in the correction of ID. Methods: Evaluation of thyroid histology reports over a 6 year period in BI and a 5 year period in the JHB area. Results: Region of BI: 278 patients with histology reports-60 were malignancies (21.2 %): 31 papillary carcinomas, 22 follicular cancers (18 follicular carcinomas and 4 Hürthle cell tumours), 3 medullary carcinomas and 4 anaplastic carcinomas. Region of JHB: 136 histology reports- 33 were malignancies (24.3 %): 13 papillary carcinomas, 15 follicular cancers (10 follicular carcinomas and 5 Hürthle cell tumours), 1 medullary carcinoma, 3 anaplastic carcinomas and 1 metastatic carcinoma into the thyroid. There was an overlap in the frequencies of all histology types, of particular relevance in the relatively high anaplastic carcinoma incidences and in the papillary to follicular carcinoma ratios which was close to 1 in both areas- BI area ratio: 1.4 and JHB area ratio: 0.87, with overlapping 95 % CI's, also confirmed by the results of the chi-square calculations. Conclusions: During the study periods evaluated both study areas displayed pathology patterns usually found in ID. Public information regarding the negative consequences of ID combined with the availability of affordable iodized salt are likely to achieve the goal of the elimination of ID. Sea based nutrition, (naturally iodine containing), may also contribute to the elimination of ID, particularly at times when salt restriction tends to be generally advised. [ABSTRACT FROM AUTHOR]

A 10 year old dog was presented for necropsy with the history of sudden death. Post mortem examination revealed congestion with areas of red hepatisation in lungs. The left inguinal mammary gland was diffusely enlarged and the cut section revealed hemorrhagic areas with cystic spaccs. Large numbers of pleomorphic cells were observed in impression smear of the mass and condensed chromatins with prominent nuclci were also seen. Histopathological examination revealed anaplastic carcinoma with micrometastasis in lungs. Liver was yellow in colour and hard in consistency. The kidneys were atrophic with irregular surface. [ABSTRACT FROM AUTHOR]

Development of mural nodules in mucinous or serous ovarian tumors are exceptional. These nodules can be benign or malignant. The author reports the seventh case of mucinous ovarian tumor associated with both sarcoma-like mural nodules and anaplastic carcinoma, in a 58-year-old, post-menopausal Caucasian female. The patient underwent surgery, followed by adjuvant chemotherapy for a pT1aN0 lesion. Shortly after completion of chemotherapy, diffuse metastases appeared. Second-line chemotherapy by anthracyclin was administered. After one cycle, disease progression with ascites was observed. Third-line chemotherapy by gemcitabine was decided. The prognosis of these tumors is poor, depending on the characteristics of the mural nodule. No consensus for treatment exists after surgery. [ABSTRACT FROM AUTHOR]

Copyright of Journal Africain D'Hépato-Gastroentérologie is the property of Lavoisier and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Aims To describe a series of anaplastic thyroid carcinomas that mimicked primary head and neck squamous cell carcinoma ( HNSCC) by virtue of both morphology and clinical presentation. Methods and results Seven cases were identified in a 15-year period where a biopsy of an airway lesion that appeared to be squamous cell carcinoma was, in fact, anaplastic thyroid carcinoma. The tumours had squamous and/or spindle cell morphology, with only the squamous component being apparent in the airway biopsy. Some tumours arose within metaplastic ( n = 3) or atypical ( n = 3) epithelium, supporting the diagnosis of a primary mucosal tumour. Positive PAX8 ( n = 5) and TTF-1 ( n = 4) staining was identified. Conclusions An endotracheal presentation of anaplastic thyroid carcinoma with squamous morphology may be misdiagnosed as a primary head and neck squamous cell carcinoma. PAX8 and TTF-1 expression are helpful in making the distinction, but the problem lies in suspecting a thyroid carcinoma in what appears to be a straightforward diagnosis of HNSCC. [ABSTRACT FROM AUTHOR]

Anaplastic thyroid carcinoma is a significantly fatal endocrine neoplasm, with an average survival time of 4-12 months following diagnosis. The present study reports the case of a 57-year-old male patient who presented to the Bağcılar Training and Research Hospital (Istanbul, Turkey) due to swelling in the neck and difficulty swallowing. The jugular mass biopsy results were consistent with a diagnosis of anaplastic thyroid cancer. The patient was regarded to have advanced-stage subcarinal, paratracheal, aortopulmonary, trancheobronchial and mediastinal lymphadenopathies and exhibited a good prognosis following chemotherapy. However, the patient succumbed one month later due to the emergence of diffuse skin lesions. The histopathological and immunohistochemical assessment of the skin biopsy displayed the characteristics of the underlying thyroid carcinoma. [ABSTRACT FROM AUTHOR]

Primary leiomyosarcomas of the thyroid gland are extremely rare. we report a case of a 72 year-old women with a painful growing mass of the left neck with skin fistula. The patient underwent a lobectomy. The tumor histology showed spindle-shaped cells arranged in interlacing fascicles that expressed desmine and Hcaldesmone, but were negative for cytokeratins and thyroglobulin. Total body CT scan didnt show any other tumor. The patient died two months after surgery. Primary thyroid leiomyosarcoma may be mistaken for other tumors, such as anaplastic or medullary carcinomas. Therefore, the diagnosis is difficult and requires numerous clinical, radiological, and pathological investigations. [ABSTRACT FROM AUTHOR]

Primary undifferentiated carcinoma of the small intestine is an extremely rare neoplasm. Here, we report a case of primary undifferentiated carcinoma that arose from the ileum in a 65-year-old woman. Laboratory data revealed anemia and slightly elevated inflammatory parameters. Computed tomography showed a heterogeneous mass in the pelvic cavity, and magnetic resonance imaging revealed that the margin of the tumor mass was clear. Positron emission tomography using 18F-fluoro-2-deoxy- d-glucose (FDG) showed accumulation of FDG on the tumor mass with a standardized uptake value of 8.3. Partial resection of the ileum to remove the tumor was performed under a clinical diagnosis of small intestinal carcinoma. The tumor was nodulated and had a circumscribed margin 6.5 × 5.5 × 4 cm in diameter. Microscopically, the tumor was composed of giant polygonal cells with cellular atypia. Immunohistochemical examination revealed that the tumor cells expressed epithelial markers including AE1/AE3, CAM5.2, and EMA; however, lymphocytic, mesenchymal, and gastrointestinal stromal tumor markers were not expressed. We made a final diagnosis of primary undifferentiated carcinoma of the small intestine. The prognosis of patients with undifferentiated carcinoma of the small intestine is very poor. To improve the outcome of treatment, early and accurate diagnosis is essential, and additional therapy, including multimodality adjuvant therapy or the administration of novel molecular targeted drugs, should be considered. [ABSTRACT FROM AUTHOR]

The presence of pleomorphic tumor giant cells in thyroid carcinomas of follicular cell origin is always worrisome for the pathologist as they first of all refer to anaplastic carcinoma, one of the most aggressive human malignancies. However, non-anaplastic pleomorphic giant cells are well described in other thyroid diseases, most often benign. In this paper, we describe four cases of papillary thyroid carcinoma displaying pleomorphic tumor giant cells with features that differ from those of anaplastic carcinoma. Pleomorphic giant cells were admixed with the underlying thyroid carcinoma and constituted from 5% to 25% of the tumor. Cytologically, they had an abundant eosinophilic cytoplasm with large and irregular nuclei. Compared to pleomorphic giant cells of anaplastic carcinoma, they reproduced the growth pattern of the underlying carcinoma, had a low mitotic index without necrosis or inflammation, and were reactive with thyroglobulin and thyroid-specific transcription factor-1 and strongly and diffusely positive for cytokeratin AE1/AE3. After 16-84 months of follow-up, patients are relapse-free and still alive. These cases show that pleomorphic tumor giant cells arising in papillary thyroid carcinomas do not always represent dedifferentiation and progression to anaplastic carcinoma. Distinction among these processes is critical as their treatment and prognosis are very different. [ABSTRACT FROM AUTHOR]

Bergmann F, Moldenhauer G, Herpel E, Gaida M M, Strobel O, Werner J, Esposito I, Sebens Müerköster S, Schirmacher P & Kern M A (2010) Histopathology 56, 440–448 Expression of L1CAM, COX-2, EGFR, c-KIT and Her2/neu in anaplastic pancreatic cancer: putative therapeutic targets? Aims: Undifferentiated (anaplastic) pancreatic cancer and undifferentiated pancreatic carcinoma with osteoclast-like giant cells (giant cell tumour) are rare variants of pancreatic ductal adenocarcinoma. Representing biologically highly aggressive neoplasms, they are frequently diagnosed at an advanced stage. The response to established chemo- or radiochemotherapeutic treatment regimens is poor, and undifferentiated pancreatic cancer generally has a dismal prognosis. As additional therapeutic options have not yet been investigated in undifferentiated pancreatic cancer, the aim was to analyse the expression of putative therapeutic targets that have shown promising results in various other neoplasms. Methods and results: Fifteen cases of undifferentiated pancreatic cancer (seven containing osteoclast-like giant cells) were investigated clinicopathologically and immunohistochemically for putative therapeutic targets. Whereas L1CAM, cyclooxygenase (COX)-2 and epidermal growth factor receptor (EGFR) were found to be significantly expressed in 80%, 93% and 87% of the investigated tumours, respectively, there was no substantial expression of c-kit (CD117) and there was no detectable expression of Her2/neu. Conclusions: The expression of L1CAM, COX-2 and EGFR in the majority of undifferentiated pancreatic carcinomas suggests that they might represent targets for adjuvant therapy in anaplastic pancreatic cancer. On the other hand, c-kit and Her2/neu seem to have no relevance for the therapy of these tumours. [ABSTRACT FROM AUTHOR]

We report a case of anaplastic carcinoma of the pancreas with production of granulocyte-colony stimulating factor (G-CSF) in a 59-year-old male. He was referred to our hospital with a chief complaint of epigastralgia and suffered from leukocytosis. Differential diagnosis included pancreatic tumors and submucosal tumor of the stomach, but definite preoperative diagnosis could not be made. He underwent distal pancreactomy, total gastrectomy with Roux-en-Y reconstruction and splenectomy. He recovered uneventfully postoperatively and was discharged from hospital on the 14th postoperative day. Histological examination showed anaplastic carcinoma of the pancreas. Since the peripheral leukocyte count was sharply decreased after the operation, we suspected the tumor would be producing G-CSF. Then immunohistochemistry showed a positive stain in the tumor. Therefore, we diagnosed the tumor as anaplastic carcinoma of the pancreas producing G-CSF. Three months after the resection, local recurrence was detected by abdominal computed tomography. The patient died of hemorrhagic shock due to tumor invasion of the intestine 8 months after the operation. [ABSTRACT FROM AUTHOR]

Parathyroid carcinoma is a rare neoplasm that accounts for only 1–3% of cases of primary hyperparathyroidism. Parathyroid carcinoma is a well-differentiated tumor that is sometimes difficult to differentiate histopathologically from its benign counterpart, parathyroid adenoma. The molecular mechanism of parathyroid carcinogenesis remains unknown, and investigators have reported that abnormalities of the p53 gene do not play a significant role in parathyroid carcinogenesis, unlike in other human malignancies. The present report describes parathyroid carcinoma with anaplastic transformation of differentiated parathyroid carcinoma in a patient with primary hyperparathyroidism. Nuclear accumulation of p53 protein was found in anaplastic carcinoma cells but not in differentiated carcinoma cells. Polymerase chain reaction–single-strand conformation polymorphism followed by direct sequencing showed that anaplastic carcinoma cells carried a missense mutation at codon 248 (CGG to CAG) of the p53 gene, while the remaining differentiated carcinoma cells had the wild-type p53 gene. These findings suggest that the p53 gene mutation is associated with anaplastic transformation of parathyroid carcinoma. [ABSTRACT FROM AUTHOR]

Vascular lesions are one of the most controversial issues in thyroid pathology. The differential diagnosis includes benign lesions on one side, i.e., endothelial reactive hyperplasia (Masson’s “hemangioma”) in goiter and hemangioma, and malignant tumors on the other, i.e., angiosarcomas and undifferentiated (angio)sarcomatoid carcinomas. Benign reactive endothelial hyperplasia with atypias mimicking malignant tumors may occur in long-standing nodular goiter, as a result of spontaneous hemorrhage followed by granulation tissue and fibrous organization. Alternatively, it may follow a fine-needle aspiration biopsy (FNAB) procedure. Angiosarcoma is a rare primary malignant thyroid tumor, mainly observed in endemic goiter areas displaying morphologic and phenotypical similar to those typical of angiosarcomas in other locations (including focal cytokeratin expression). The distinction between angiosarcoma and (angio)sarcomatoid anaplastic carcinoma is difficult and the true existence of angiosarcoma has been challenged. Other extremely rare vascular lesions or mimics in the thyroid include benign hemangioma and pseudo-angiosarcomatous variant of medullary carcinoma. The differential diagnosis between benign and malignant vascular conditions in FNAB material is extremely challenging, and the cytopathology report should be remarkably cautious, especially in poorly cellular and highly hemorrhagic cases: atypias in endothelial cells are not per se indicative of malignancy, being a common feature of reactive endothelial hyperplasia in infracted goiter nodules as well. [ABSTRACT FROM AUTHOR]

A 59-year-old Japanese man presented with a giant submucosal tumor with ulceration during follow-up of duodenal ulcer. Pancreaticoduodenectomy was undertaken, and subsequent histological examination of the tumor disclosed anaplastic carcinoma of the pancreas head. The carcinoma components contained adenocarcinoma and squamous cell carcinoma. Additionally, undifferentiated spindle or pleomorphic cells were seen in continuity with the carcinoma component. Undifferentiated neoplastic cells with rhabdoid features and with hyaline globule-like structures positive for PAS stain with diastase pretreatment were also observed. Immunohistochemically, cytoplasmic inclusions corresponding to rhabdoid features showed aggregates of vimentin. Ultrastructurally, hyaline globule-like structures corresponded to lysosomes. Finally, we report here the first case of anaplastic carcinoma of the pancreas with hyaline globule-like structures. [ABSTRACT FROM AUTHOR]

Malignant tumours of the thyroid are generally classified as either well-differentiated thyroid carcinoma, which is composed of papillary and follicular carcinoma, or undifferentiated/anaplastic thyroid carcinoma (ATC). ATC is not only the most lethal disease in the field of endocrine surgery but also one of the most aggressive tumours characterized by an almost invariable fatal outcome, which only very rarely exceeds a 1-year course. The impact of surgical resection in association with external beam radiation on ATC outcome has been extensively investigated also in studies based on multicentric database, and there is a general agreement on the significance of a complete resection of the tumour. It has been difficult up to now to collect data regarding chemotherapy adjuvant treatment. In spite of the lack of an extensive review about the results of this kind of treatment by itself or as part of a multimodal approach, it seems that among the several chemotherapy agents experienced, none proved to influence significantly ATC prognosis. Neither doxorubicin (the most commonly used) nor other drugs, such as cisplatin, bleomycin, fluorouracil or cyclophosphamide, showed any real efficacy in controlling the disease. The most recent development in this field seems to be represented by the possibility offered by PPARg agonists; even more promising might be the use of adenovirus-mediated p53 tumour suppressor gene therapy or BMP-7. All these new therapies need further confirmation coming from ongoing clinical trials such as those involving the use of vascular and growth factor-targeted agents. [ABSTRACT FROM AUTHOR]

Background. Anaplastic thyroid carcinoma (ATC), although rare, is one of the most aggressive human cancers, and patients with ATC have extremely poor prognoses despite various therapeutic measures. We wished to determine the prognostic factors of survival and effect of treatment on survival rate in patients with ATC. Methods. We retrospectively reviewed the medical records of the 121 patients (41 men and 80 women) diagnosed with ATC from January 1995 to June 2004 at 5 major referral centers in Korea. Results. Mean patient age at diagnosis was 64 ± 11 years (range, 17–84 years). Of the 121 patients, 11 (9%) had intrathyroidal tumors, 69 (57%) had extrathyroidal tumors or lymph node involvement, 29 (24%) had distant metastases, and 12 had no data about staging (9%). The mean tumor diameter was 5.5 ± 2.5 cm (range, 0.5–17.0 cm). At a median follow-up of 41 months (range, 26–122 months), 8 patients were alive. Median survival time was 5.1 months. The disease-specific survival rates were 42% at 6 months, 16% at 12 months, and 9% at 24 months. Sixteen patients (13%) received only supportive care, 25 (21%) received surgery alone, 20 (16%) received radiation treatment or chemotherapy without surgery, and 60 (50%) received surgery plus radiation treatment or chemotherapy. Multivariate analysis showed that age less than 60 years, tumor size less than 7 cm, and lesser extent of disease were independent predictors of lower disease-specific mortality. Conclusions. Long-term survival is possible for ATC patients less than 60 years old and with small localized tumors. Although aggressive multimodal therapy, including surgery, radiation treatment, and chemotherapy, was not significantly associated with improved survival, we advocate aggressive multimodal therapy in selected ATC patients with good prognostic factors. © 2007 Wiley Periodicals, Inc. Head Neck 2007 [ABSTRACT FROM AUTHOR]

Frequency of a BRAFV600E mutation in anaplastic thyroid carcinoma, which is thought to be derived mainly from papillary carcinoma by multi-step carcinogenesis, is much lower than that in papillary carcinomas. To clarify this phenomenon, we analysed BRAFV600E mutation in 20 cases of anaplastic carcinoma and 13 accompanying differentiated carcinomas. Among twenty cases of anaplastic carcinomas, nine and four accompanied papillary and follicular carcinomas, respectively. BRAFV600E mutation was found in four (20%) cases. BRAFV600E mutation was found in three of nine (33.3%), none of four and one of seven (14.3%) anaplastic carcinomas with papillary carcinoma, follicular carcinoma and without differentiated components, respectively. All three papillary carcinomas accompanied by anaplastic carcinoma with a BRAFV600E mutation were also shown to have a BRAFV600E mutation. In summary, BRAFV600E mutation was occasionally observed in anaplastic carcinomas with papillary carcinoma, and the low frequency of BRAFV600E mutation in anaplastic carcinoma was thought to be due to the low frequency of anaplastic carcinomas with papillary carcinoma. These findings raise a question about the classical model of anaplastic transformation and suggest some roles of thyroid cancer stem cells in the generation of anaplastic carcinoma.British Journal of Cancer (2007) 96, 1549–1553. doi:10.1038/sj.bjc.6603764 www.bjcancer.com Published online 24 April 2007 [ABSTRACT FROM AUTHOR]

Aims: The diagnosis of follicular thyroid carcinomas is mainly based on capsular and vascular invasion. The aim of this study was to determine the diagnostic relevance of nuclear features, inflammation and stromal changes. Methods and results: Anisokaryosis, chromatin pattern, nucleolus, nuclear pleomorphism, nuclear/cytoplasmic ratio, necrosis, stromal changes and tumour interstitial lymphocytes (TIL) were analysed in adenomatous hyperplastic nodules (39), adenomas (43) and carcinomas (28 minimally invasive, 48 widely invasive and 27 anaplastic). Ki67 immunostaining, in situ end labelling (ISEL) for apoptosis and the Ki67/ISEL index were analysed by topographical compartments. Variables were compared by histological diagnosis using Fisher's exact test, analysis of variance and Student's t-tests and considered significant if P < 0.05. TIL were absent in 96% of neoplasms and 54% of adenomatous hyperplastic nodules. Conspicuous nucleoli, increased nuclear–cytoplasmic ratio and coexistent apoptosis–myxoid changes distinguished minimally invasive carcinomas from adenomas. The most specific variables of high-grade carcinoma were vasculonecrotic patterns, nuclear hyperchromatism and pleomorphism. A kinetic advantage predominated in the internal compartments of benign lesions and in the peripheral compartments of malignant lesions. Conclusions: Follicular carcinomas show up-regulation of proliferation markers and the distinctive topographical kinetic profiles provide a basis for the distinction between benign and malignant and an explanation for the circumscription and encapsulation of benign lesions. [ABSTRACT FROM AUTHOR]