Initial Chemotherapy for Locally Advanced and Metastatic NUT Carcinoma.

INTRODUCTION: NUT carcinoma (NC) is an underdiagnosed and aggressive poorly differentiated or squamous cell cancer. A subset of NC is sensitive to chemotherapy, but the optimal regimen is unknown. Experts have recommended platinum- and ifosfamide-based therapy based on case reports. METHODS: Patients with pathologically confirmed NC with known survival outcomes after chemotherapy and consented to participate in a worldwide registry were studied. Results were summarized using descriptive methods. RESULTS: The study included 118 patients with NC. Median age was 34 (range: 1-82) years, 39% were women, and 61% harbored a BRD4::NUTM1 fusion. Patients received platinum (74%) or ifosfamide (26%, including regimens with both, 13%). Of 62 patients with nonmetastatic disease, 40% had a thoracic primary. Compared with platinum-based chemotherapy, patients who received ifosfamide-based chemotherapy had nominally higher progression-free survival (12 mo: 59% [95% CI: 32-87] versus 37% [95% CI: 22-52], hazard ratio = 0.68 [0.32, 1.42], p = 0.3) but not overall survival (OS). Among the 56 patients with metastatic disease, 80% had a thoracic primary. Ifosfamide had an objective response rate (ORR) of 75% (six of eight) and platinum had an ORR of 31% (11 of 36). Nevertheless, there was no difference in progression-free survival or OS. The 3-year OS of the entire cohort was 19% (95% CI: 10%-28%). Of the 11 patients alive greater than 3 years, all presented with nonmetastatic and operable or resectable disease. CONCLUSION: There is a numerically higher ORR for ifosfamide-based therapy compared with platinum-based therapy, with limited durability. OS at 3 years is only 19%, and development of effective therapies is an urgent unmet need for this patient population.

Small Cell Neuroendocrine Carcinoma of the Parotid Gland: An Uncommon Example of Incompletely Encapsulated Tumor Including S100 Protein-Positive Clear Cells.

Small cell carcinoma is rare in salivary glands and has recently been termed small cell neuroendocrine carcinoma. We herein describe an uncommon example arising in the parotid gland. The patient was a 75 yearold Japanese male who had swelling in the right parotid area. He underwent a superficial lobectomy and, after a histological diagnosis was made, a total parotidectomy. Histologically, the tumor had a thick hyalinized capsule that was incomplete, beyond which the tumor invaded into the surrounding parotid parenchyma. The tumor consisted of typical small basophilic cells intermingled with bland clear cells, between which a gradual transition was observed both inside and outside the capsule. Small basophilic cells were immunoreactive for chromograninA as well as synaptophysin, while clear cells were positive for S100 protein. The Ki-67 labeling rate reached 30-40% at the high points of small basophilic cells, but clear cells were minimally labelled. The present case was considered a dedifferentiated carcinoma of the parotid gland, possibly with acinic cell carcinoma as a precursor. This tumor could also be considered a "mixed exocrine-endocrine carcinoma," which may explain the histogenesis of neuroendocrine carcinomas in non-endocrine organs that are not included in the diffuse (dispersed) neuroendocrine system, such as the parotid gland.

Investigation of pre-operative demographic, biochemical, sonographic and cytopathological findings in low-risk thyroid neoplasms.

OBJECTIVE: The present article analyses pre-operative demographic, biochemical, sonographic and histopathological characteristics of low-risk thyroid neoplasms (LRTNs), with a focus on four subgroups, "well-differentiated carcinoma-not otherwise specified" (WDC-NOS), "non-invasive follicular thyroid neoplasm with papillary like nuclear features" (NIFTP), "well-differentiated tumours of uncertain malignant potential" (WDT-UMP) and "follicular tumour of uncertain malignant potential" (FT-UMP). METHODS: The study retrospectively analyzed the histopathology of 2453 malignant thyroids and the final analyses included 99 cases diagnosed with LRTNs. The demographic and clinical features, pre-operative thyroid function, ultrasonography results, cytopathology results, histopathology results and prognostic classifications were assessed. RESULTS: The groups were similar demographic characteristics and the majority of clinical data, including comorbidities, thyroid function tests, thyroid cancer/neck radiotherapy history. NIFTPs represented 69.7% of all LRTNs. All (100%) WDT-UMPs had solitary nodules. Index nodule volume differed among the groups (p = .036), it was the lowest in WDC-NOS [0.68 (0.63-0.72 cc)] and highest in FT-UMP [12.6 (0.5-64 cc)]. Echogenicity findings were similar. Index nodule TIRADS demonstrated a significant difference (p = .021) but index nodule halo sign and BETHESDA scores were similar in all groups. The diameter, localisation and multicentric structure of LRTNs were again similar for all groups. Finally, prognostic scores suggested similar outcomes in all groups. CONCLUSION: The majority of LRTNs were NIFTPs in our population and all WDT-UMPs were solitary lesions. Index nodule volume was the most essential discriminating sonographic finding but further research must be performed before discriminatory potential can be described.

Role of prophylactic central neck lymph node dissection for papillary thyroid carcinoma in the era of de-escalation.

Thyroid cancer is the most common endocrine malignancy. While there has been no appreciable increase in the observed mortality of well-differentiated thyroid cancer, there has been an overall rise in its incidence worldwide over the last few decades. Patients with papillary thyroid carcinoma (PTC) and clinical evidence of central (cN1) and/or lateral lymph node metastases require total thyroidectomy plus central and/or lateral neck dissection as the initial surgical treatment. Nodal status in PTC patients plays a crucial role in the prognostic evaluation of the recurrence risk. The 2015 guidelines of the American Thyroid Association (ATA) have more accurately determined the indications for therapeutic central and lateral lymph node dissection. However, prophylactic central neck lymph node dissection (pCND) in negative lymph node (cN0) PTC patients is controversial, as the 2009 ATA guidelines recommended that CND "should be considered" routinely in patients who underwent total thyroidectomy for PTC. Although the current guidelines show clear indications for therapeutic CND, the role of pCND in cN0 patients with PTC is still debated. In small solitary papillary carcinoma (T1, T2), pCND is not recommended unless there are high-risk prediction factors for recurrence and diffuse nodal spread (extrathyroid extension, mutation in the BRAF gene). pCND can be considered in cN0 disease with advanced primary tumors (T3 or T4) or clinical lateral neck disease (cN1b) or for staging and treatment planning purposes. The role of the preoperative evaluation is fund-amental to minimizing the possible detrimental effect of overtreatment of the types of patients who are associated with low disease-related morbidity and mortality. On the other hand, it determines the choice of appropriate treatment and determines if close monitoring of patients at a higher risk is needed. Thus, pCND is currently recommended for T3 and T4 tumors but not for T1 and T2 tumors without high-risk prediction factors of recurrence.

Osteosarcoma of the Larynx: A Case Report and Review of Literature.

The most common malignant laryngeal tumors are squamous cell carcinomas (SCCs), and other types such as sarcomas are rare. Osteosarcomas of the larynx are extremely rare within the subset of sarcomas, with very few cases reported in the literature. This cancer has a predilection for elderly males, in the sixth to eighth decades of life. Associated symptoms include hoarseness, stridor, and dyspnea. It is known to spread early and has a high rate of recurrence. We present the case of a 73-year-old male, a former smoker, who presented to the clinic with severe dyspnea and progressive hoarseness and was found to have a large exophytic mass arising from the epiglottis. A biopsy of the mass showed a poorly differentiated cancer with osteoid and new bone formation. He then underwent surgical removal of the mass, followed by radiation, and achieved clinical remission. However, a surveillance positron emission tomography (PET) scan 14 months later showed a hypermetabolic lesion in the left lung. Biopsy revealed metastatic osteosarcoma, and unfortunately, this cancer also spread to the brain. In this report, we will focus on the histological features of this rare malignancy and treatment options.

Primary small cell thyroid carcinoma combined with poorly differentiated thyroid carcinoma, evidence for a common origin: A case report.

Primary small cell thyroid carcinomas are extremely rare and there is still debate about their classification as a distinct disease entity. The present case report reports a small cell carcinoma (SCC) combined with poorly differentiated thyroid carcinoma (PDTC) in a 34 year old man. The tumor consisted of ~80% PDTC and ~20% SCC. The PDTC component was positive for cytokeratin and thyroid transcription factor-1 (TTF-1), and negative for calcitonin, chromogranin and synaptophysin. The SCC component was positive for synaptophysin and CD56, and negative for calcitonin, chromogranin and TTF-1. Seven months after thyroid surgery, two new lung nodules were detected. Histologically and immunohistochemically, the lung tumors were similar to the SCC component of the thyroid carcinoma. The mutational status of cancer-related genes was assessed using targeted next-generation sequencing in both the thyroid and lung, which identified similar genetic alterations. The histogenesis of SCC was evaluated through NGS analysis of the two cancer components.

Case report: Thymoid differentiated carcinoma of thyroid: Two cases.

Objective: Thymoid carcinoma of the thyroid gland is a rare thyroid tumor, which is often presented in case reports. Methods: The clinical data of two patients with thymic carcinoma of the thyroid gland were retrospectively reviewed. Results: Case 1: a middle-aged woman who was admitted to the hospital because of "progressive enlargement of the anterior cervical mass for 8 months." Color Doppler ultrasound and CT showed malignant tumor with high possibility of bilateral cervical lymph node metastasis. Total thyroidectomy and bilateral central cervical lymph node dissection were performed. Lymph node biopsy showed the metastasis of small cell undifferentiated thyroid carcinoma. Because the biopsy pathological result was not consistent with the pathology of the primary lesion, immunohistochemistry was performed again, and the final diagnosis was thymic carcinoma in the thyroid gland. Case 2: the patient was an elderly man who was admitted to the hospital due to hoarseness for half a month. During the operation, the tumor invaded the trachea, esophagus, internal jugular vein, common carotid artery, and surrounding tissues. Palliative resection of the tumor was performed. The tumor postoperative pathology suggested thymoid carcinoma of the thyroid gland. It recurred and compressed the trachea 4 months after the operation, resulting in dyspnea of the patient, and finally tracheotomy was performed to alleviate the symptoms. Conclusion: Case 1 showed multiple differences in pathological diagnosis, suggesting that the lack of specific imaging and clinical manifestations of thymoid-differentiated thyroid carcinoma made the diagnosis so difficult. Case 2 progressed rapidly, suggesting that thymoid-differentiated thyroid carcinoma was not always inert, and the treatment and follow-up should follow the principle of individualization.

Fine needle aspiration cytology of metastatic SMARCA4-deficient sinonasal teratocarcinosarcoma: First report in literature.

Inactivating mutations of SMARCA4 and accompanying loss of BRG1 immunoexpression were recently identified in majority of sinonasal teratocarcinosarcomas (TCS). These rare and aggressive neoplasms have potential for nodal metastasis, presenting opportunities for diagnosis on fine needle aspiration cytology (FNAC). However, their cytological features have not been described till date. A 22-year-old male was diagnosed to have SMARCA4-deficient TCS on a nasal mass biopsy, and was started on neoadjuvant chemotherapy. Four months later, FNAC from cervical lymph nodes showed predominantly discohesive tumor cells with moderate to abundant cytoplasm and enlarged vesicular nuclei with prominent nucleoli. Occasional cohesive fragments showed ovoid to spindled tumor cells attached to fibrovascular cores. Few loosely cohesive cells with scant cytoplasm and nuclei having stippled chromatin, and rhabdoid cells were also seen. Frequent mitoses, apoptosis and nuclear streaking were evident. Overt squamous or glandular differentiation was absent. Tumor cells showed loss of BRG1 immunostaining and ß-catenin immunopositivity on a cell block, consistent with metastatic SMARCA4-deficient TCS. The diversity of cell types in SMARCA4-deficient TCS can result in a broad spectrum of cytological features that overlap with that of other regional metastatic tumors including neuroendocrine carcinoma, olfactory neuroblastoma and melanoma. Further, all components of TCS as seen in the primary tumor may not be present in nodal metastases. Thus, SMARCA4-deficient TCS should be considered in the differential diagnosis of metastatic poorly/undifferentiated malignancies in cervical lymph node aspirates, and appropriate ancillary tests viz. BRG1 immunostaining employed for accurate diagnosis.

Advanced Differentiated Thyroid Cancer: A Complex Condition Needing a Tailored Approach.

Differentiated thyroid cancers (DTCs) are slow-growing malignant tumours, including papillary and follicular carcinomas. Overall, prognosis is good, although it tends to worsen when local invasion occurs with bulky cervical nodes, or in the case of distant metastases. Surgery represents the main treatment for DTCs. However, radical excision is challenging and significant morbidity and functional loss can follow the treatment of the more advanced forms. Literature on advanced thyroid tumours, both differentiated and undifferentiated, does not provide clear and specific guidelines. This emerges the need for a tailored and multidisciplinary approach. In the present study, we report our single-centre experience of 111 advanced (local, regional, and distant) DTCs, investigating the rate of radical excision, peri-procedural and post-procedural complications, quality of life, persistence, recurrence rates, and survival rates. Results are critically appraised and compared to the existing published evidence review.

Aggressive variants of follicular cell-derived thyroid carcinoma: an overview.

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.

ZEB1 expression is frequently detected in undifferentiated and de-differentiated carcinomas, but is not specific among endometrial carcinomas.

AIMS: The pathological diagnosis of undifferentiated and de-differentiated endometrial carcinomas (UC/DCs) is prognostically important. However, undifferentiated components may be confused with other subtypes, particularly grade 3 endometrioid carcinomas (G3ECs). Zinc finger E-box binding homeobox 1 (ZEB1) has recently been identified as a promising marker because it is frequently expressed in the undifferentiated components of UC/DCs, but not in other carcinomas. Therefore, we herein evaluated the diagnostic utility of ZEB1 with an emphasis on distinguishing between UC/DCs and G3ECs using an expanded cohort of endometrial carcinomas and carcinosarcomas. METHODS AND RESULTS: Immunostaining for ZEB1 was performed on whole-tissue sections of 19 UC/DCs, 194 non-UC/DC endometrial carcinomas and 29 carcinosarcomas. Staining was defined as negative (< 5%), focal (5-50%) and diffuse expression (> 50%). ZEB1 was expressed in 84% of the undifferentiated components of UC/DCs (diffuse in 14, focal in two). Focal expression was observed in eight non-UC/DC endometrial carcinomas and diffuse expression in seven, with the latter comprising G3ECs (four of 76), serous carcinoma (one of 37), clear cell carcinoma (one of 21) and neuroendocrine carcinoma (one of three). Epithelial differentiation was morphologically and immunohistochemically less evident in G3ECs and neuroendocrine carcinoma with diffuse ZEB1 expression. All carcinosarcomas showed diffuse ZEB1 expression in their sarcomatous components. CONCLUSION: Immunostaining for ZEB1 was sufficiently sensitive to detect undifferentiated components. Diffuse ZEB1 expression showed high specificity for distinguishing between undifferentiated components and G3ECs; however, ZEB1 expression was not entirely specific to UC/DCs. The integration of ZEB1 into the diagnosis of UC/DCs requires careful examination to exclude other tumours, such as less differentiated G3ECs, neuroendocrine carcinomas and carcinosarcomas.

Myeloid Sarcoma Expressing Keratins and Mimicking Carcinoma-Case Report and Literature Review.

Unusual presentations of otherwise common hematopoietic neoplasms are a well-recognized diagnostic challenge. Herein, we present a case study of a previously healthy 64 year old woman with myeloid sarcoma whose diagnosis was delayed by an unusual immunohistochemical staining pattern, including cytokeratin expression, by the neoplastic cells and by possible anchoring bias introduced by radiographic and flow cytometric immunophenotyping reports. This case study emphasizes the need to integrate clinical, radiographic, histologic, and immunophenotyping data for rapid and accurate tissue diagnoses while being wary of the lack of specificity for many common immunophenotypic markers.

Chromophobe renal cell carcinoma-like thyroid carcinoma: possible misdiagnosis as metastatic renal cell carcinoma.

To date, multiple thyroid cancer variants have been reported. Herein, we report a rare case of chromophobe renal cell carcinoma-like thyroid carcinoma (CRETHCA) in a 60-year-old woman, for which the morphologic findings resembled those of chromophobe renal cell carcinoma (ChRCC). ChRCC of the kidney is characterized by large polygonal tumor cells with distinct cell borders, perinuclear clearing, multiple binucleate cells, and strongly positive immunostaining for paired box gene 8 (PAX8) and carbonic anhydrase IX (CA IX). In our case, the thyroid gland tumor was incidentally detected by routine medical screening without sufficient medical information; it showed similar histology and immunohistochemical features to ChRCC and was initially misdiagnosed as metastatic ChRCC. Additional tests, including kidney computed tomography and positron emission tomography, revealed no abnormalities in the patient's kidney; therefore, we diagnosed the tumor as CRETHCA. Focal weak staining for thyroid transcription factor 1 (TTF-1) was the only supporting evidence that it was a primary thyroid neoplasm. To the best of our knowledge, this is the second report of CRETHCA in literature. This novel variant is very difficult to distinguish from metastatic ChRCC and can be a diagnostic challenge for pathologists. Further studies of similar cases should be done to define this new entity.

Evaluation of Therapeutic Targets in Histological Subtypes of Bladder Cancer.

Histologically, bladder cancer is a heterogeneous group comprising urothelial carcinoma (UC), squamous cell carcinoma, adenocarcinomas (ACs), urachal carcinomas (UrCs), and small cell neuroendocrine carcinomas (SCCs). However, all bladder cancers have been treated so far uniformly, and targeted therapy options are still limited. Thus, we aimed to determine the protein expression/molecular status of commonly used cancer targets (programmed cell death 1 ligand 1 (PD-L1), mismatch repair (MMR), androgen and estrogen receptors (AR/ER), Nectin-4, tumor-associated calcium signal transducer 2 (Tacstd2, Trop-2), epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), and fibroblast growth factor receptor 3 (FGFR3)) to give first insights into whether patients with SCC, AC/UrCs, and squamous-differentiated carcinomas (Sq-BLCA) of the bladder could be eligible for targeted therapies. In addition, for MMR-deficient tumors, microsatellite instability was analyzed. We completed our own data with molecular data from The Cancer Genome Atlas (TCGA). We present ratios for each drug and cumulative ratios for multiple therapeutic options for each nonurothelial subtype. For example, 58.9% of SCC patients, 33.5% of AC/UrCs patients, and 79.3% of Sq-BLCA patients would be eligible for at least one of the analyzed targets. In conclusion, our findings hold promise for targeted therapeutic approaches in selected patients in the future, as various drugs could be applied according to the biomarker status.

p53 protein expression in synchronously occurring dedifferentiating stages of thyroid cancer in a patient with neurofibromas: A case report.

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

Lenvatinib for poorly differentiated carcinoma of the anterior mediastinum.

We describe a Case of a 74-year-old Japanese man with poorly differentiated carcinoma of the anterior mediastinum. The patient underwent anterior mediastinal tumor resection through median sternotomy. The tumor, 7.0 × 5.0 cm, had invaded surrounding tissues (pericardium, right lung, right and left brachiocephalic veins, and superior vena cava). Complete resection of the tumor was not performed. One month after the operation, the patient developed multiple pulmonary metastases, right pleural dissemination, and carcinomatous pleurisy. He was treated with lenvatinib, a novel multi-kinase inhibitor, to which the metastasis responded favorably. This case reports for the first time the clinical usefulness of lenvatinib for poorly differentiated carcinoma of the anterior mediastinum. Management of side effects by several methods, including suspending use of medication on weekends (called a weekends-off strategy), is another strong argument to continue lenvatinib administration.

Review of SMARCA4 (BRG1)-deficient carcinomas following a malignant pleural effusion specimen confounded by reduced claudin-4 expression.

SMARCA4-deficient neoplasms are recently characterized high-grade malignancies associated with a poor prognosis. The SMARCA4 gene encodes BRG1, which is part of the SWI/SNF complex. SMARCA4-deficient neoplasms have an undifferentiated, often rhabdoid morphology, and demonstrate loss of BRG1 nuclear expression on immunohistochemistry. These neoplasms have become increasingly recognized and diagnosed in tissue specimens, but their features in cytologic specimens are poorly defined in the literature. The review is introduced by a diagnostically challenging case of a SMARCA4-deficient carcinoma involving a pleural fluid specimen in which the carcinoma cells demonstrated greatly reduced claudin-4 expression in the setting of strong, diffuse BerEP4 expression. Most of the malignant cells also demonstrated positive cytoplasmic staining for PAS and all were PAS-diastase negative, suggesting that the cytoplasm contained glycogen granules.

Coexisting well-differentiated and anaplastic thyroid carcinoma in the same primary resection specimen: immunophenotypic and genetic comparison of the two components in a consecutive series of 13 cases and a review of the literature.

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.

NUT Carcinoma Arising from the Parotid Gland: A Case Report and Review of the Literature.

NUT carcinoma is an aggressive carcinoma with an overall poor survival outcome. The mediastinum and head and neck area, especially the sinonasal region, are among the common sites of disease. Histopathological diagnosis of NUT carcinoma is often very challenging due to its overlapping features with other poorly differentiated carcinomas. We report a case of NUT carcinoma arising from the parotid gland of a young female patient. Primary NUT carcinoma of salivary gland is very rare, with only 15 such cases reported in the literature to date. Our case highlights the diagnostic challenges associated with such lesions.

Head-to-Head Comparison of p63 and p40 in Non-Neuroendocrine Carcinomas of the Tubal Gut.

OBJECTIVES.: With targeted agents, characterizing carcinomas of the gastrointestinal (GI) tract has become more important. We aim to determine the usefulness of p40 in classifying GI tract carcinomas. METHODS.: Seventy-five GI carcinomas including 28 squamous cell carcinomas (SCC), 2 adenosquamous carcinomas (ASCA), 21 poorly differentiated carcinomas (PDCA), and 24 adenocarcinomas (AdCA; control group) were stained for p40, p63, and CK5/6. Tumors were scored from 0 to 5 based on extent of staining and marked as positive (score >2) or negative. RESULTS.: p63 was positive in 100% of SCC/ASCA and 12.5% of AdCA. p40 was positive in 92.5% of SCC/ASCA and 4.1% of AdCA. In the PDCA subset, a panel including p63, p40, and MOC31 was the best way to accurately classify most cases. CONCLUSIONS.: p63 and CK5/6 are more sensitive but less specific than p40 for SCC/ASCA in GI carcinomas. In PDCA, a panel approach including p63, CK5/6, and p40 may be best in classifying these cases.