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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: 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]

Abstract 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.

Introduction: Primary thyroid lymphoma is defined as a lymphoma involving only the thyroid gland, or thyroid gland with regional lymph nodes without contiguity or metastasis to other areas at the time of diagnosis. Hashimoto’s thyroiditis is a known risk factor for the disease. It responds well to chemotherapy but since it is a rare clinical entity, the diagnosis is often missed, thereby subjecting the patient to extensive surgery. Case report: A 69 years old male presented with rapidly progressive swelling in front of neck for 10 days associated with dysphagia, odynophagia and dyspnoea. He had right lobe thyromegaly with multiple cervical lymphadenopathy with ultrasonographic risk stratification of TIRADS 5. Diagnosis was clinched by core biopsy report on immunohistochemistry as Diffuse Large B Cell Non-Hodgkin’s Lymphoma. Positron emission tomography computerized scan revealed 18-fluorodeoxyglucose avid grossly enlarged thyroid lobes and isthmus with multiple bilateral cervical lymph nodes. Documenting the stage of disease as III E, he was managed with Chemo-immunotherapy consisting of RCVP regime with complete remission. Conclusion: Primary thyroid lymphoma with extra-thyroid involvement can be rapidly progressing and life threatening. However, timely investigation leads to correct diagnosis, appropriate curative medical management and can avoid unwarranted surgery.

Ovarian mucinous cystic tumours with mural nodules are rare tumours of the ovary that are often missed out during diagnosis. They are classified under the ovarian mucinous surface epithelial-stromal tumours. These mural nodules can be sarcoma-like (benign), anaplastic carcinoma, sarcomas, or mixed malignant (carcinosarcoma). However, very few cases of anaplastic malignant mural nodules have been reported. Here, we present a case of a borderline ovarian mucinous cystadenoma with anaplastic mural nodule that has sarcomatoid differentiation, in a 39-year-old woman who presented with a 1-year history of progressive abdominal swelling and pain. There were intraoperative findings of huge right ovarian cystic tumour with omental and umbilical deposits. Differential diagnosis of possible germ cell tumours, vascular tumours, melanoma, sarcoma and sarcoma-like nodules were ruled out with routine histology (Haematoxylin & Eosin), histochemical (reticulin) and immunohistochemical stains (CK AE1/3+, CD30+, AFP-, HCG-, EMA-, S100 protein-, CD31-, and CD34-) and the final diagnosis of a mural nodule of anaplastic carcinoma with sarcomatoid differentiation in a borderline ovarian mucinous cystadenoma established. Unfortunately, due to the aggressive nature of the tumour and disease progression, the patient passed on a few months after the surgery. This rare tumour, especially the ones with anaplastic carcinoma or mixed tumours, usually has an aggressive clinical course with most patients presenting late when the disease is advanced with poor clinical outcomes as is seen with the index patient. A high index of suspicion of this tumour with early detection and a multidisciplinary approach to its management is advised. [ABSTRACT FROM AUTHOR]

More than 90 % of newly diagnosed cases of endocrine cancer occur in the thyroid gland. Introduction of fine needle puncture of the thyroid gland, with the classification of cytological material according to the Bethesda system, has become the cornerstone of the diagnosis of malignant neoplasms of the thyroid gland. However, traditionally in this classification there remains a weak link called a follicular tumor (category IV). The detection of a follicular tumor in the cytological material does not allow one to reliably classify the mass as benign or malignant and requires surgical intervention with morphological verification. In recent years, the possibilities of molecular genetic testing have improved markedly. Follicular tumors tend to accumulate mutations, which over time can lead to malignant transformation, but can also be used as a method of timely diagnosis. This review analyzes the literature on the possibilities of molecular genetic testing in assessing the malignant potential of follicular formations of the thyroid gland.

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]

Abstract 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

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]

We describe the case of a young patient with a borderline mucinous ovarian tumor that progressed into ipsilateral ovarian anaplastic carcinoma in only 3 months with metastasis to the contralateral ovary and extensive spread in the pelvic and abdominal regions. The mucinous tumor harbored micro-foci of intraepithelial carcinoma, but no mural nodules, microinvasion, or invasive adenocarcinoma were detected. Notably, a rupture on the ovarian mass and low-grade pseudomyxoma peritonei were present. Next-generation sequencing identified an identical KRAS mutation in the mucinous tumor and anaplastic carcinoma, while the latter had KRAS gene amplification and CDKN2A, MPL and TP53 mutations. These findings indicate the anaplastic carcinoma might have arisen via recurrence, malignant transformation and dedifferentiation of the former low-grade mucinous tumor. We consider that the mass rupture and pseudomyxoma peritonei were high-risk factors for recurrence, while genetic mutations were key drivers of progression. Accordingly, such cases may benefit from active surgical treatment and early chemotherapy.

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: Carcinoma arising from a thyroglossal duct cyst (TGDC) is a uniquely rare, but well described, occurrence. As the majority of these malignancies favor a papillary subtype, the phenomenon of a mixed anaplastic and squamous cell variant has been virtually unobserved. Case: A 63 year-old woman presented with an enlarging submental mass and left-sided otalgia, which was confirmed to be mixed anaplastic and squamous cell carcinoma originating from a TDGC via a CT scan and open biopsy. The mass was treated with radiation and chemotherapy. At 32 months after treatment, the patient demonstrated complete response to therapy with no signs of recurrence or metastasis. Conclusion: Anaplastic carcinoma originating from a TGDC is an exceedingly rare malignancy variant that may respond to treatment consisting of definitive radiation and chemotherapy. The co-presentation of anaplastic carcinoma with a more differentiated cancer is consistent with the suggestion that this poorly-differentiated malignancy may have arisen from a pre-existing cancer of the TGDC.

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]

Abstract Background Undifferentiated carcinoma (UC) of the pancreas is a rare subtype of pancreatic cancer. Although UC has been considered a highly aggressive malignancy, no clinical studies have addressed the efficacy of chemotherapy for unresectable UC. Therefore, we conducted multicenter retrospective study to investigate the efficacy of chemotherapy in patients with UC of the pancreas. Methods This multicenter retrospective cohort study was conducted at 17 institutions in Japan between January 2007 and December 2017. A total of 50 patients treated with chemotherapy were analyzed. Results The median overall survival (OS) in UC patients treated with chemotherapy was 4.08 months. The details of first-line chemotherapy were as follows: gemcitabine (n = 24), S-1 (n = 12), gemcitabine plus nab-paclitaxel (n = 6), and other treatment (n = 8). The median progression-free survival (PFS) was 1.61 months in the gemcitabine group, 2.96 months in the S-1 group, and 4.60 months in the gemcitabine plus nab-paclitaxel group. Gemcitabine plus nab-paclitaxel significantly improved PFS compared with gemcitabine (p = 0.014). The objective response rate (ORR) was 4.2% in the gemcitabine group, 0.0% in the S-1 group, and 33.3% in the gemcitabine plus nab-paclitaxel group. Gemcitabine plus nab-paclitaxel also showed a significantly higher ORR compared with both gemcitabine and S-1 (gemcitabine plus nab-paclitaxel vs. gemcitabine: p = 0.033; gemcitabine plus nab-paclitaxel vs. S-1: p = 0.034). A paclitaxel-containing first-line regimen significantly improved OS compared with a non-paclitaxel-containing regimen (6.94 months vs. 3.75 months, respectively; p = 0.041). After adjustment, use of a paclitaxel-containing regimen in any line was still an independent predictor of OS (hazard ratio for OS, 0.221; 95% confidence interval, 0.076–0.647; p = 0.006) in multiple imputation by chained equation. Conclusions The results of the present study indicate that a paclitaxel-containing regimen would offer relatively longer survival, and it is considered a reasonable option for treating patients with unresectable UC.

Abstract 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.

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.

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]

Sarcomatoid or anaplastic carcinomas arising within epithelial ovarian neoplasms are rare, particularly within serous tumors of the ovary, and carry a poor prognosis. Here we present the case of a patient initially diagnosed with low grade serous ovarian carcinoma arising within a serous borderline tumor (atypical proliferative serous tumor). She underwent rapid progression of disease and was found to have anaplastic/sarcomatoid carcinoma on biopsy of recurrence. These findings prompted pathologic re-review of the original neoplasm, which demonstrated a microscopic focus of sarcomatoid/anaplastic carcinoma.

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]

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.

Anaplastic thyroid carcinoma (ATC), one of the most aggressive malignancies, is extremely rare in childhood. We present a case of 5-yearold child who presented with rapidly progressing thyroid swelling and stridor, for which she underwent emergency tracheostomy and biopsy. Histopathological features were suggestive of ATC and the patient died within two months after diagnosis. ATC, though very rare in childhood, should be kept in the differential diagnoses of rapidly enlarging neck masses in children. To the best of our knowledge, this is the youngest case of ATC reported in literature.

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]

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]