Variant Of Carcinoma Research Articles

Urinary tract cytology showing variant morphology and divergent differentiation.

Urothelial carcinoma represents a diverse group of tumours with distinct histologic subtypes, each exhibiting unique cytomorphologic features, architectural growth patterns, and/or well-developed aberrant differentiation. In fact, there are more than 13 subtypes of urothelial carcinoma recognized in the 2022 WHO classification of tumours in the urinary tract. The identification of these subtypes is crucial for an accurate diagnosis of urothelial carcinoma, and many have important clinical implications. Variant/divergent features may coexist with conventional high-grade urothelial carcinoma (HGUC) or present with 100% variant morphology. In urinary tract cytology (UTC), urothelial carcinoma can display divergent differentiation, such as squamous, glandular, or small cell carcinoma differentiation. The use of cell block preparations and immunohistochemistry with available residual urine can enhance diagnostic accuracy. On the other hand, identifying urothelial carcinoma variants, including nested, micropapillary, and plasmacytoid subtypes, poses significant challenges in UTC. Many cases of these variants are only detected retrospectively after variant histology has been established from resection specimens. Moreover, some variants exhibit features inconsistent with the diagnostic criteria for HGUC according to the Paris System for Reporting Urinary Tract Cytology. Nevertheless, the rarity of pure variant morphology and the occurrence of some false negatives for these variant cases are essential to maintain the specificity of UTC overall. This review covers the histology, cytomorphology, and important clinical aspects observed in urothelial carcinoma exhibiting divergent differentiation and various urothelial carcinoma variants detected in UTC.

New insights into histopathological features of Warthin-like papillary thyroid carcinoma

Background. The Warthin-like variant of papillary thyroid carcinoma (WLPTC) is a rare papillary thyroid carcinoma that is considered to be a subtype of the oncocytic variant. Purpose of the study: to present the diagnostic and clinical features, the oncological and surgical management of a patient with WLPTC as well as its discussion with other relevant studies. Materials and methods. We report a case of Warthin-like papillary thyroid carcinoma in a 31-year-old woman with Hashimoto thyroiditis. Results. The patient was admitted to the hospital with the presence of a node in the thyroid gland. Thyroid ultrasound showed a 24-mm nodule with oval shape and irregular contours in the left lobe. A fine-needle aspiration biopsy was performed, and a diagnosis of papillary thyroid carcinoma was made. The patient underwent thyroidectomy, bilateral modified and central neck dissection, lymphadenectomy. Histopathological examination suggested a WLPTC coexisting with chronic thyroiditis, metastases to the lymph nodes 2, 3, 4 on the left and 6 neck compartments. The patient underwent postoperative I131 ablation therapy. Conclusions. WLPTC is a recently described variant of papillary thyroid cancer that is frequently associated with lymphocytic thyroiditis. The correct cytological and histomorphological features are of utmost importance to render the diagnosis of WLPTC for better management. A surgical and postoperative treatment is identical to that in classic differentiated thyroid cancer, having a favorable outcome due to a low recurrence rate. A surgical management should be thyroidectomy and dissection of central neck compartment as well as lateral dissection in cases of suspicions for metastases in the lymph nodes or metastases confirmed preoperatively by a fine-needle aspiration biopsy.

AKAP12 inhibits esophageal squamous carcinoma cell proliferation, migration, and cell cycle via the PI3K/AKT signaling pathway

Esophageal squamous cell carcinoma (ESCC) consistently ranks as one of the most challenging variants of squamous cell carcinomas, primarily due to the lack of effective early detection strategies. We herein aimed to elucidate the underlying mechanisms and biological role associated with A-kinase anchoring protein 12 (AKAP12) in the context of ESCC. Bioinformatic analysis had revealed significantly lower expression level of AKAP12 in ESCC tissue samples than in their non-cancerous counterparts. To gain deeper insights into the potential role of AKAP12 in the progression of ESCC, we conducted a single-gene set enrichment analysis of AKAP12 on ESCC datasets. Our findings suggested that AKAP12 exhibits functions inhibiting cell cycle progression, tumor proliferation, and epithelial-mesenchymal transition. To further validate our findings, we subjected ESCC cell lines to AKAP12 overexpression using CRISPR/Cas9-SAM. In vitro analyses demonstrated that increased expression of AKAP12 significantly reduced cell proliferation, migration, and cell cycle progression. Simultaneously, genes associated with this biological role undergo corresponding regulatory shifts. These observations provided valuable insights into the biological role played by AKAP12 in ESCC progression. In summary, AKAP12 shows promise as a new potential biomarker for early ESCC diagnosis, offering potential advantages for subsequent therapeutic intervention and disease management.

Malignant struma ovarii- Report of a rare case

Struma ovarii is a highly specialized form of mature ovarian teratoma in which the ovary contains >50% of thyroid tissue. It accounts for 1 – 3% of benign teratomas of the ovary. Malignant transformation is observed in 5-37% cases of struma ovarii. Peak age of incidence 4 - 5th decade with excellent prognosis. We report a rare form of malignant struma ovarii, composed of a follicular variant of papillary thyroid carcinoma with capsular invasion. A65-year-old hypertensive postmenopausal female presented with complaints of pain in abdomen, pelvic mass, frequent micturition, since 3 days. A pelvic sonogram showed an enlarged heterogenous right ovarian mass of sized 12 x 9 x 5 cm, with solid cystic lesion. Left ovary was unilocular and cystic of sized 5.5 x 4 x 3 cm. The uterus and cervix appeared to be normal. She underwent an exploratory laparotomy, and a total abdominal hysterectomy with bilateral salpingo-oophorectomy. Based on histopathological and radiological features an impression of follicular variant of papillary carcinoma of thyroid with capsular invasion was favoured. : The patient was successfully treated with total abdominal hysterectomy with bilateral salpingo-oopherectomy. There are no sign of recurrence and metastasis two months after surgery. Patient is under regular follow up. : Malignant struma ovarii is a medical rarity and very few studies have been reported.

SAT532 A Rare Case of Thyroid Carcinoma Noted in a Patient with Thyroid Nodule Showing Prior Benign Biopsy and Prior Negative Molecular Testing

Abstract Disclosure: M.M. Hillhouse: None. P. Madhavan: None. F.M. Woron: None. Background: Molecular studies have a high sensitivity for ruling out malignancy (1). This patient was diagnosed with the follicular variant of papillary thyroid carcinoma despite negative molecular testing and benign cytology in multiple prior biopsies. Clinical Case: 31 y.o. female with a past medical history of Hashimoto's disease on levothyroxine presented for follow up of thyroid nodules. She does not have a family history of thyroid cancer or personal history of neck radiation. The patient was noted to have a right thyroid nodule around 14 years of age and this was monitored during her childhood. The nodule measured 2.3 x 0.6 cm on ultrasound in 2015. The nodule measured 2.0 x 1.6 x 1.5 cm in 2017. FNA in 2017 revealed benign cytology (Bethesda II). On ultrasound in 03/2019, the nodule measured 2.2 x 1.5 x 1.8 cm. The nodule demonstrated a greater than 20% increase in all dimensions on ultrasound images in 12/2020 to 2.9 x 2.0 x 2.6 cm. A repeat ultrasound in 04/2021 demonstrated no significant change in size. Repeat FNA performed in 07/2021 demonstrated clusters of follicular cells in flat and microfollicular groups and was interpreted as atypia of undetermined significance (Bethesda III). AFIRMA testing was benign (∼4% of malignancy. The nodule increased in size to 3.5 x 2.6 x 3.1 cm on ultrasound in 07/2022. It appeared solid and hyperechoic and was classified as TI-RADS 3. A new 0.8 cm nodule on the left lobe was also identified. Repeat FNA of the right nodule in 09/2022 demonstrated macrophages, colloid and groups of follicular cells and was classified as non-diagnostic (Bethesda I). She reported difficulty breathing in the supine position and she underwent a right hemithyroidectomy and isthmusectomy in 11/2022. Pathology results were remarkable for invasive encapsulated follicular variant of papillary thyroid carcinoma with focal angioinvasion and tumor capsular invasion. The margins were negative for tumor. The parenchyma was consistent with lymphocytic thyroiditis. Ultrasound after interval right hemithyroidectomy in 12/2022 in an outside facility demonstrated an unchanged subcentimeter left thyroid nodule and multiple bilateral anterior cervical/level 6 lymph nodes suspicious for metastatic disease given the absence of hilum. Patient is currently undergoing repeat imaging and work up for the lymphadenopathy. Conclusion: This case study highlights the importance of maintaining high clinical suspicion for thyroid malignancy in cases of increasing thyroid nodule size and compressive symptoms despite negative cytological and molecular testing.

THU681 Change In The Clinicopathological Characteristics And Outcomes Of Pediatric Thyroid Carcinoma In Korea: Focusing On Data From A Tertiary Hospital In Korea

Abstract Disclosure: J. Yoo: None. D. Leem: None. H. Ryu: None. H. Park: None. J. Kim: None. Y. Oh: None. T. Kim: None. S. Kim: None. J.H. Chung: None. Introduction: The incidence of thyroid carcinoma in adults in Korea increased until 2012, but has declined rapidly since then. However, the incidence of pediatric thyroid carcinoma increased until 2013, decreased slightly, and then increased again. Changes in the clinicopathological characteristics of pediatric thyroid carcinoma over time have not yet been elucidated. In this study, we aimed to evaluate the changes in the clinicopathological characteristics and outcomes of pediatric thyroid carcinoma from 1995 to 2022. Subjects and Methods: A total of 170 patients under the age of 19 years who were diagnosed with differentiated thyroid carcinoma at tertiary hospital in Seoul, Korea were enrolled. The patients were divided into four groups based on the year of initial surgery: 1995 – 2005 (n = 33), 2006 – 2010 (n = 46), 2011 – 2015 (n = 57), and 2016 – 2022 (n = 34). Results: The age at diagnosis, gender, primary tumor size, T stage, N stage, and M stage did not significantly differ among the four groups. Also, there was no significant difference over time in the route of detection (symptomatic vs. asymptomatic; P for trend = 0.519). The incidence of diffuse sclerosing variant of papillary thyroid carcinoma tended to increase over time (P=0.06). Surgical extent (P for trend = 0.001) and cumulative radioactive iodine (RAI) dose (P for trend < 0.001) significantly decreased over time. Nevertheless, the disease-free survival among the four groups did not change during the median follow-up 115.5 (62.3 – 155.3) months (log-rank P = 0.451). Conclusions: Although the overall incidence of pediatric thyroid carcinoma is gradually increasing in Korea, surgical extent and cumulative RAI dose significantly decreased and the clinicopathological characteristics and the disease-free survival did not change over time. Presentation: Thursday, June 15, 2023

SAT573 Incidental Discovery Of CHEK2 Mutation With Papillary Thyroid Cancer

Abstract Disclosure: F.L. Thelmo: None. A. Mehrab: None. S.A. Jabbour: None. A 66-year-old white male had been following steadily with our practice for greater than a decade where we were managing his post-ablative hypothyroidism from toxic multinodular goiter 20 years prior. Many years later, the patient developed hypercalcemia and was found to have asymptomatic primary hyperparathyroidism. He did not meet any indication for parathyroidectomy. In early January 2021, the patient was referred to a clinical geneticist at the behest of his wife as she was concerned that he had a very high rate of cancer in his family. The patient had a total of 11 relatives who either currently had or previously died from a malignancy, of which only one of them was on his maternal side. The patient’s father had a personal history of breast cancer, prostate cancer, and bone cancer at the time he passed away. The patient underwent a full panel of genetic testing and was found to be positive for a CHEK2 (Checkpoint Kinase 2) mutation. Around this time, the patient’s hypercalcemia escalated up to 13mg/dL without evidence of hypoalbuminemia. Decision was made to pursue surgery. In order to localize the parathyroid adenoma, a technetium sestamibi scan and a neck ultrasound were obtained. Sestamibi scan showed increased parathyroid adenomatous activity in the left lower portion of the thyroid bed and ultrasound confirmed the left lower pole parathyroid adenoma with a dominant hypoechoic 2.5cm TI-RADS 5 thyroid nodule which on biopsy was suspicious for papillary thyroid carcinoma. The patient underwent a total thyroidectomy in addition to the parathyroidectomy. Pathological evaluation confirmed a parathyroid adenoma and a classic variant of papillary thyroid carcinoma without angioinvasion and minimal extrathyroidal invasion classified as Stage 1 T2N0M0. The patient did not meet criteria for treatment with radioactive iodine and at the time of this writing is doing well, on levothyroxine with low-normal TSH and undetectable thyroglobulin with normal serum calcium. He has no other signs of malignancy at this time. However, given his CHEK2 mutation, he will require ongoing multi-disciplinary cancer surveillance. We would like to draw attention to this not uncommon oncogenic mutation that due to its incomplete penetrance does not always present such a staggering family history of cancer and thus may go undetected. CHEK2 mutations occur in roughly 1% of all individuals who undergo genetic evaluation for cancer. The mutation moderately increases the patient and their family’s risk for multiple malignancies including: breast, thyroid, prostate, stomach, kidney, and plasma cell malignancies. Individuals with this mutation should be screened thoroughly by a multi-disciplinary team based on the severity of their inherited mutation. These individuals should also receive counseling on family planning if conception is desired. Presentation: Saturday, June 17, 2023

SAT509 The Clinical Significance of Cribriform Morular Thyroid Carcinoma

Abstract Disclosure: G. Soh: None. K. Sek: None. S. Yang: None. M. Nga: None. S. Mok: None. We present two young (aged below 30) female patients who were diagnosed with the rare cribriform morular thyroid carcinoma. Both patients presented with neck swellings and underwent total thyroidectomy for the thyroid malignancies. The histological diagnosis prompted subsequent genetic evaluation. Both patients demonstrated genotypic and phenotypic evidence of familial adenomatosis polyposis (FAP) syndrome. One of the patients had a mutation which resulted in a premature translational stop signal in the adenomatous polyposis coli (APC) gene. She was eventually diagnosed with adenocarcinoma in 2 colonic polyps and underwent a curative pan-proctocolectomy. The other patient was diagnosed clinically with FAP as she had multiple (30-40) colonic polyps which were tubular adenomas. She had a variant of unknown significance in the APC gene. She declined surgery and remained on colonoscopic surveillance. Both patients’ thyroid cancers are in clinical remission. While uncommon, diagnosing cribriform-morular thyroid carcinoma is significant as 25 to 30% of patients harbour genetic mutations in the APC gene on chromosome 5q21. This is associated with FAP syndrome, an autosomal dominant genetic syndrome characterized by young-onset colonic polyposis, usually of malignant potential. Additionally, these patients may exhibit features of Gardner’s syndrome, a subset of FAP syndrome in which patients can develop extra-colonic manifestations such as osteomas of the mandible and supernumerary teeth. Histologically, cribriform morular thyroid carcinoma are well circumscribed and show a variable combination of follicular, cribriform, papillary, trabecular, solid and morular patterns. There is nuclear and cytoplasmic staining for beta catenin, as the inactivating APC mutation causes a loss of beta catenin destruction complex, impeding beta catenin degradation and increasing its nuclear translocation. This is a key event in thyroid tumorigenesis. The diagnosis of cribriform morular thyroid carcinoma should alert the clinician about the possibility of FAP with consideration for further clinical and genetic evaluation to confirm the diagnosis. References1)Cameselle-Teijeiro, J. M., Peteiro-González, D., Caneiro-Gómez, J., Sánchez-Ares, M., Abdulkader, I., Eloy, C., Melo, M., Amendoeira, I., Soares, P., & Sobrinho-Simões, M. (2018). Cribriform-morular variant of thyroid carcinoma: A neoplasm with distinctive phenotype associated with the activation of the Wnt/β-catenin pathway. Modern Pathology, 31(8), 1168–1179. https://doi.org/10.1038/s41379-018-0070-2 2)Peiling Yang, S., & Ngeow, J. (2016). Familial non-medullary thyroid cancer: Unraveling the Genetic Maze. Endocrine-Related Cancer, 23(12). https://doi.org/10.1530/erc-16-0067 Presentation Date: Saturday, June 17, 2023

THU680 Cytologic And Molecular Assessment Of Isthmus Thyroid Nodules

Abstract Disclosure: S. Jasim: None. Y. Chen: Employee; Self; Veracyte, Inc. Stock Owner; Self; Veracyte, Inc. R. Jiang: Employee; Self; Veracyte, Inc. Stock Owner; Self; Veracyte, Inc. Y. Hao: Employee; Self; Veracyte, Inc. Stock Owner; Self; Veracyte, Inc. J. Huang: Employee; Self; Veracyte, Inc. Stock Owner; Self; Veracyte, Inc. J.P. Klopper: Employee; Self; Veracyte, Inc. Stock Owner; Self; Veracyte, Inc. R.T. Kloos: Employee; Self; Veracyte, Inc. Stock Owner; Self; Veracyte, Inc. T.C. Brown: None. Thyroid nodules arising in the isthmus are more likely to be malignant and demonstrate more aggressive behavior relative to thyroid nodules from either thyroid lobe. Preliminary studies of papillary thyroid cancers (PTC) studied in The Cancer Genome Atlas (TCGA) indicate molecular profiles that may explain the more aggressive phenotype of isthmic PTC, including an increased ERK signaling molecular profile. The goal of this study was to interrogate the Veracyte Afirma thyroid nodule database and assess cytologic and molecular differences of thyroid aspirates sent for Afirma Genomic Sequencing (GSC) testing from isthmus nodules relative to lobar nodules. Samples from isthmus nodules represented 4.8% of all samples. Most Afirma nodules had indeterminate cytology (ITN, Bethesda III or IV) and there were more ITN samples from the thyroid lobes (95.7%) compared to the isthmus (91.8%). For Bethesda V or VI nodules, the proportion from the isthmus was almost double that from the lobes (8.2% vs 4.3%). There were no significant differences observed in the Afirma benign or suspicious result of ITN samples comparing isthmus versus lobar location. Analysis of molecular alterations in Afirma suspicious nodules from ITN and Bethesda V-VI nodules showed that isthmus nodules had twice the frequency of BRAFV600E mutations compared to lobar nodules (21% vs 10%), an increased frequency of ALK/NTRK/RET fusions (4.6% vs 2.5%), and a lower frequency of NRAS (7.7% vs 13%) and HRAS (4.5% vs 8.2%) variants (all comparisons significant (p < 0.001)). Additionally, isthmus nodules had significantly higher BRAF-like signature, ERK signaling, and follicular-mesenchymal transition scores compared to lobar nodules (p < 0.01). In summary, thyroid nodules sent for Afirma molecular testing arising from the isthmus are more likely to have Bethesda V and VI cytology and, amongst Afirma suspicious ITN and Bethesda V and VI lesions, have higher levels of molecular markers of aggressiveness relative to lobar nodules. This study expands upon the data seen in PTCs from the TCGA as most thyroid tumors referred for molecular testing have Bethesda III and IV cytology and thus are enriched for follicular lesions including follicular variants of PTC and follicular carcinomas. Future studies should investigate the final histopathology of these molecularly tested isthmus nodules as well as oncologic outcomes. Presentation: Thursday, June 15, 2023

SAT550 Warthin-like Variant of Papillary Thyroid Carcinoma: An Even Rarer Presentation

Abstract Disclosure: J. Kunadia: None. S. Chablani: None. Introduction: We present a rare case of Warthin-like variant of papillary thyroid carcinoma (WLPTC) with later development of a second primary malignancy. Clinical Case: A 56 year old female with hypertension, hyperlipidemia, ulcerative colitis, asthma, and a strong family history of cancer presented in 2017 for evaluation of an enlarged thyroid gland noted by her primary care provider. Patient was asymptomatic and denied prior thyroid disease and head or neck radiation. Labs demonstrated normal TSH and free T4 levels. TPO antibodies were elevated to 1,155 IU/mL (reference range 0.0 – 5.5 IU/mL). Thyroid US was notable for a diffusely enlarged thyroid gland containing a 1.4 x 0.6 x 1.0 cm solid, hypoechoic nodule without calcifications in the upper pole of the right lobe. Shared decision-making resulted in a plan for continued surveillance. Repeat thyroid US in 2018 demonstrated that this nodule had increased in volume by 56.25%, now measuring 1.4 x 0.75 x 1.25 cm. Fine needle aspiration (FNA) biopsy was performed and positive for papillary thyroid carcinoma (PTC). Patient underwent total thyroidectomy; pathology revealed a 1.2 x 1 x 0.9 cm WLPTC and 0.2 cm papillary thyroid microcarcinoma. There was no evidence of extrathyroidal extension, angioinvasion, or lymph node involvement. Follow-up neck US in 2020 demonstrated a 0.4 cm hypoechoic ovoid structure in the left thyroid bed and an enlarged but morphologically normal-appearing right level II lymph node. Repeat neck US in 2021 showed the appearance of a new 2.8 cm right level II lymph node; FNA was positive for malignancy with negative thyroid transcription factor-1 staining and undetectable thyroglobulin. Patient underwent an excision biopsy of the lymph node, and pathology was consistent with metastatic adenoid cystic carcinoma (ACC). A right submandibular gland lesion detected on subsequent MRI head and neck was resected and confirmed to be the primary source of ACC. Patient was treated with adjuvant radiation therapy with adequate response to therapy. Conclusion: WLPTC is a rare subtype of PTC that accounts for 0.2-1.9% of cases and carries a strong association with Hashimoto’s thyroiditis. It is histologically characterized by papillary architecture, oncocytic changes, nuclear features of PTC, and dense lymphoplasmacytic infiltration of the papillary cores. WLPTC is considered to have a favorable prognosis given its low frequency of lymphovascular invasion and low recurrence risk. This case also highlights the importance of keeping a broad differential when evaluating new findings on neck US in patients with a history of thyroid cancer. Metastases to cervical lymph nodes most commonly occur from head and neck tumors. However, to date, only one other case of PTC with second primary malignancy of salivary ACC has been reported. Presentation Date: Saturday, June 17, 2023

A rare case of pulmonary endobronchial spindle cell carcinoma with liver metastasis along with concurrent cutaneous neurofibroma

Spindle cell carcinoma is one of the histological variants of pulmonary sarcomatoid carcinoma. It is a rare, poorly differentiated, highly malignant, and rapidly growing non-small cell carcinoma of the lung. Information about pulmonary spindle carcinoma incidence, clinical features, and immunohistochemical markers are not well known compared to other variants of sarcomatoid carcinoma. Most sarcomatoid carcinoma features mimic non-small cell carcinoma, so it is easily misdiagnosed. Cutaneous neurofibroma with primary lung spindle cell carcinoma has not been reported in any previous literature. Here we report a rare endobronchial sarcoma with liver metastasis and concurrent skin neurofibroma.

A case report of an oncocytic variant of chromophobe renal cell carcinoma in South Africa

A case report of an oncocytic variant of chromophobe renal cell carcinoma in South Africa

Macrofollicular Architecture in Invasive Encapsulated Follicular Variant of Papillary Thyroid Carcinoma: A Pitfall in Thyroid Practice.

Predominantly macrofollicular architecture in invasive encapsulated follicular variant of papillary thyroid carcinoma (IEFVPTC-MF) is rare and often a cause of misinterpretation during pre-operative work-up and histopathology evaluation. We comprehensively evaluated the radiological, cytological, gross, microscopic, molecular and follow-up characteristics of four such cases, intending to increase its recognition and add our experience to the limited literature available. All such histopathologically-proven cases of IEFVPTC-MF were retrieved from the departmental archives. The clinical details, thyroid ultrasound, cytology and thyroid scan findings were reviewed. Allele-specific PCR for BRAF p.V600E, KRAS, NRAS, and HRAS mutations, and FISH assays for ETV6::NTRK3 fusion and RET fusions were performed. There were four cases of IEFVPTC-MF diagnosed between 2021 and 2022, involving two males and two females. The median age at presentation was 27years, and the duration of the disease was 1-10years. Thyroid ultrasound was TR1 (benign; n = 1), TR2 (not suspicious; n = 2), or TR4 (moderately suspicious; n = 1). Cytology was categorized as nondiagnostic (n = 1), benign (n = 1), andatypia of undetermined significance (n = 1). The three nodules with available cytology smears showed abundant colloid. Cells were arranged as sheets/microfollicles/clusters. Nuclei were predominantly round with minimal/focal elongation, membrane irregularity, and cellular crowding. On gross examination, cut surfaces of the tumors showed variable amounts of colloid. The tumors were solid-cystic. Histopathology revealed partially encapsulated multinodular tumors. There were prominent pseudopapillae projecting into the lumina of macrofollicles. Nuclei were predominantly round with variable nuclear atypia, including chromatin clearing and multifocal presence of nuclear grooves. Pseudoinclusions were identified in two. Molecular analysis revealed NRAS codon 61 mutation and ETV6::NTRK3 fusion in one case each. Two patients had cervical lymph node and hematogenous metastases. Post-radio-active iodine, the response was structurally incomplete (n = 2), indeterminate (n = 1) and excellent (n = 1). Macrofollicular architecture in invasive encapsulated follicular variant of papillary thyroid carcinoma is a major pitfall in thyroid oncology practice. Long-standing disease, and ultrasonographic and cytological features that overlap with benign disease, often lead to underdiagnosis during pre-operative evaluation. As patients may consequently develop distant metastases and have inadequate treatment response, there is a need for more vigilant understanding of the spectrum of macrofollicular thyroid disease for accurate diagnosis. ETV6::NTRK3 or other fusions, when found, present opportunities for targeted therapy.

The Role of Morphology in Predicting Fumarate Hydratase-deficient Uterine Leiomyomas in Young Women.

Hereditary leiomyomatosis and renal cell carcinoma is caused by germline mutations in the fumarate hydratase (FH) gene and is associated with an increased incidence of leiomyomas and a potentially aggressive variant of renal cell carcinoma. Pathologic evaluation of uterine leiomyoma can provide an opportunity for early recognition of the syndrome. We reviewed all archived slides of the cases to identify the characteristic morphologic features described for FH-deficient leiomyomas. We performed immunohistochemistry on whole sections of patients with uterine leiomyoma to evaluate for both FH and 2-succinocysteine (2SC) expression. Of the 106 cases, 19 showed the characteristic eosinophilic nucleoli with perinuclear halos, and 24 revealed a characteristic eosinophilic cytoplasmic inclusion consisting of pink globules present within the cytoplasm. Both of these morphologic findings were present together in 15 cases, and hemangiopericytomatous vessels were detected in 23 cases. The loss of FH protein expression was detected in 14 out of 106 cases (13%), and 13 out of 106 cases (12%) were positive for 2SC. We detected 10 cases with both 2SC-positive and FH expression loss. The presence of eosinophilic nucleoli with perinuclear halos and eosinophilic cytoplasmic inclusion was associated with both loss of FH protein expression and 2SC positivity ( P < 0.001). These findings underscore the importance of hematoxylin and eosin-based predictive morphology in FH-deficient uterine leiomyomas. Therefore, morphologic assessment of uterine leiomyomas for features of FH deficiency can serve as a screening tool for hereditary leiomyomatosis and renal cell carcinoma syndrome, allowing patients to be divided according to their hereditary risk assessment.

A Detailed Histologic and Molecular Assessment of the Diffuse Sclerosing Variant of Papillary Thyroid Carcinoma

Diffuse sclerosing variant papillary thyroid carcinoma (DS-PTC) is characterized clinically by a predilection for children and young adults, bulky neck nodes, and pulmonary metastases. Previous studies have suggested infrequent BRAFV600E mutation but common RET gene rearrangements. Using strict criteria, we studied 43 DS-PTCs (1.9% of unselected PTCs in our unit). Seventy-nine percent harbored pathogenic gene rearrangements involving RET, NTRK3, NTRK1, ALK, or BRAF; with the remainder driven by BRAFV600E mutations. All 10 pediatric cases were all gene rearranged (P = .02). Compared with BRAFV600E-mutated tumors, gene rearrangement was characterized by psammoma bodies involving the entire lobe (P = .038), follicular predominant or mixed follicular architecture (P = .003), pulmonary metastases (24% vs none, P = .04), and absent classical, so-called “BRAF-like” atypia (P = .014). There was no correlation between the presence of gene rearrangement and recurrence-free survival. Features associated with persistent/recurrent disease included pediatric population (P = .030), gene-rearranged tumors (P = .020), microscopic extrathyroidal extension (P = .009), metastases at presentation (P = .007), and stage II disease (P = .015). We conclude that DS-PTC represents 1.9% of papillary thyroid carcinomas and that actionable gene rearrangements are extremely common in DS-PTC. DS-PTC can be divided into 2 distinct molecular subtypes and all BRAFV600E-negative tumors (1.5% of papillary thyroid carcinomas) are driven by potentially actionable oncogenic fusions.

Management of Cutaneous Squamous Cell Carcinoma (Clear Cell Variant) in Bovine - A Case Report

Tumors of the bovine gastrointestinal tract are rare, possibly because of the low age of the sample population (Bertone, 1990). Neoplasia in cattle carries a poor prognosis because of early adenocarcinoma metastasis and the high fatality of lymphosarcoma. Squamous cell carcinoma is the second most rude type of skin cancer, with basal cell carcinoma being the most common (Rinker et al., 2001). Squamous cell carcinoma has been documented in bovine (Musser et al., 1993). Clear-cell squamous cell carcinoma is a rare variant of squamous cell carcinoma, first described by Kuo (1980) as a skin tumor. The exact etiology is unclear, but ultraviolet radiation has been suggested as a possible cause in humans (Lawal et al., 2013). This report documents a case of cutaneous squamous cell carcinoma (clear cell variant) in perianal region of a cow and its successful surgical management.

A rare presentation of orbital spindle cell carcinoma a case report and brief review of the literature

BackgroundTo describe a case of orbital spindle cell carcinoma which presented with limbal ischemia and briefly review the literature.MethodsRetrospective case report and brief literature review.ResultsA 61-year old man presented with blepharoptosis, periorbital pain, decreased vision and limbal ischemia. He did not mention any previous illness and did not take any kind of drugs. Imaging revealed an orbital mass that was positive for SMA, Vimentin and CD99 and negative for S100. We treated the patient with chemotherapy and followed him for other complications that occurred throughout disease course.ConclusionSpindle cell carcinomas are a rare variant of squamous cell carcinoma (SCC) with dual malignant histologic differentiation of squamous and mesenchymal cells. Few cases of orbital spindle cell carcinoma have been reported, which have been either secondary to distant metastasis or regional spread. In this study, we have reported the first case of primary orbital spindle cell carcinoma presenting with limbal ischemia. Further studies are needed to describe the different clinical presentations and management strategies of this rare clinical entity.

Sclerosing mucoepidermoid thyroid carcinoma combined with autoimmune thyroiditis

Background. Sclerosing mucoepidermoid thyroid carcinoma (SMTC) is a recently recognized malignant neoplasm of the thyroid. SMTC was frst reported in 1991. It arises in a background of Hashimoto thyroiditis (HT). There are two variants of mucoepidermoid carcinoma of thyroid gland: the conventional and sclerosing variants. SMTC has recently been recognized as a separate disease entity by World Health Organization (WHO). Description of the clinical case. We present the case of a 51-year-old woman with a 2-year history of autoimmune thyroiditis with a thyroid nodule. The patient had no symptoms or signs of compression. The level of thyroid–stimulating hormone (TSH) was 15.8 (range 0.4-4.0), antibodies to peroxidase: 150 Iu/ml. Scintigraphy of the thyroid gland revealed a dominant cold nodule (1.5×2 cm) in the right lobe of the gland. The control ultrasound examination showed negative fndings. Fine needle aspiration cytology of the nodule revealed follicular lesion in a background of TH. Extrafascial thyroidectomy was performed. The patient was followed up for 10 months.

Do large thyroid nodules (≥4 cm) without suspicious cytology need surgery?

Fine-needle aspiration biopsy (FNAB) is a good diagnostic tool for thyroid nodules; however, its high false-negative rate for giant nodules remains controversial. Many clinicians recommend surgical resection for nodules >4 cm owing to an increased risk of malignancy and an increased false-negative rate. This study aimed to examine the feasibility of this approach and investigate the incidence of malignancy in thyroid nodules >4 cm without suspicious cytology based on medical records in our center. This was a retrospective analysis of 453 patients that underwent preoperative FNAB for nodules measuring >4 cm between January 2017 and August 2022 at Severance Hospital, Seoul. Among the 453 patients, 140 nodules were benign and 119 were indeterminate. Among 259 patients, the final pathology results were divided into benign (149) and cancerous (110) groups, and the prevalence of malignancy was 38.9% in the benign group and 55.5% in the indeterminate group. Among the malignancies, follicular carcinoma and follicular variants of papillary carcinoma were observed in 83% of the cytologically benign group and 62.8% of the indeterminate group. Preoperative FNAB had high false-negative rates and low diagnostic accuracy in patients with thyroid nodules >4 cm without suspicious cytologic features; therefore, diagnostic surgery may be considered a treatment option.

The Warthin-like variant of papillary thyroid carcinomas: a clinicopathologic analysis report of two cases

Abstract Obejectives Papillary thyroid carcinoma (PTC) is the most common type of thyroid carcinoma, comparising various subtypes including classical PTC (accounting for approximately 55–65 % of cases) and several variants. The identified variants include papillary microcarcinoma, encapsulated variant, follicular variant, diffuse sclerosing variant, tall cell variant, columnar cell variant, cribriform-morular variant, and Warthin-like variant (WLV-PTC). WLV-PTC is a rare malignant neoplasm. Case presentation The present study introduced two cases of WLV-PTC from Affiliated Hospital of Chengde Medical College in retrospect. The macroscopic characteristics, histological feature, immunophenotyping, gene mutations, local invasion, and distant metastasis of the tumors were observed, and the relevant literature on WLV-PTC was reviewed. The tumor cells exhibited nuclear the characteristics similar to those of classic papillary thyroid carcinoma. Immunohistochemical analysis showed strong positivity for thyroid transcription factor 1, cytokeratin 19, Galectin-3, and CK, weak positivity for thyroglobulin, and the Ki-67 proliferation index ranging from 5 to 10 %. Gene mutation analysis revealed that Case 1 had a BRAF V600E mutation, whereas Case 2 had a wild-type mutation. WLV-PTC has histological features similar to those of Warthin tumor originating from salivary gland. Conclusions The prognosis of WLV-PTC is similar to that of conventional PTC of comparable size and stage.