Adrenal Neoplasms: Lessons from Adrenal Multidisciplinary Tumor Boards.

The radiologic diagnosis of adrenal disease can be challenging in settings of atypical presentations, mimics of benign and malignant adrenal masses, and rare adrenal anomalies. Misdiagnosis may lead to suboptimal management and adverse outcomes. Adrenal adenoma is the most common benign adrenal tumor that arises from the cortex, whereas adrenocortical carcinoma (ACC) is a rare malignant tumor of the cortex. Adrenal cyst and myelolipoma are other benign adrenal lesions and are characterized by their fluid and fat content, respectively. Pheochromocytoma is a rare neuroendocrine tumor of the adrenal medulla. Metastases to the adrenal glands are the most common malignant adrenal tumors. While many of these masses have classic imaging appearances, considerable overlap exists between benign and malignant lesions and can pose a diagnostic challenge. Atypical adrenal adenomas include those that are lipid poor; contain macroscopic fat, hemorrhage, and/or iron; are heterogeneous and/or large; and demonstrate growth. Heterogeneous adrenal adenomas may mimic ACC, metastasis, or pheochromocytoma, particularly when they are 4 cm or larger, whereas smaller versions of ACC, metastasis, and pheochromocytoma and those with washout greater than 60% may mimic adenoma. Because of its nonenhanced CT attenuation of less than or equal to 10 HU, a lipid-rich adrenal adenoma may be mimicked by a benign adrenal cyst, or it may be mimicked by a tumor with central cystic and/or necrotic change such as ACC, pheochromocytoma, or metastasis. Rare adrenal tumors such as hemangioma, ganglioneuroma, and oncocytoma also may mimic adrenal adenoma, ACC, metastasis, and pheochromocytoma. The authors describe cases of adrenal neoplasms that they have encountered in clinical practice and presented to adrenal multidisciplinary tumor boards. Key lessons to aid in diagnosis and further guide appropriate management are provided. © RSNA, 2023 Online supplemental material is available for this article. Quiz questions for this article are available through the Online Learning Center.

Thyroid Carcinoma with NSD3::NUTM1 Fusion: a Case with Thyrocyte Differentiation and Colloid Production.

In this report, we present a high-grade thyroid carcinoma with an NSD3::NUTM1 fusion detected on expanded next-generation sequencing testing. Nuclear protein of the testis (NUT) carcinomas comprise high-grade, aggressive tumors characterized by rearrangements of the NUTM1 gene with various partner genes, most commonly the bromodomain protein genes BRD4 and BRD3. Approximately 10% of NUT carcinomas contain an NSD3::NUTM1 fusion. NUT carcinomas manifest as poorly differentiated or undifferentiated squamous carcinomas, and 33% show areas of mature squamous differentiation. Only exceptionally have NUT carcinomas shown histology discordant from poorly differentiated/undifferentiated squamous carcinoma, and a thyroid NUT carcinoma with histologic thyrocyte differentiation has not been described to date. Our patient's tumor exhibited mixed cytologic features suggestive of squamoid cells or papillary thyroid carcinoma cells. Overt squamous differentiation was absent, and the tumor produced colloid in poorly formed follicles. Immunophenotypically, the carcinoma was consistent with thyrocyte differentiation with expression of monoclonal PAX8, TTF1, and thyroglobulin (the last predominantly in extracellular colloid). There was zero to < 2% reactivity for proteins typically diffusely expressed in NUT carcinoma: p40, p63, and cytokeratins 5/6. NUT protein expression was equivocal, but fluorescence in situ hybridization confirmed a NUTM1 rearrangement. This exceptional case suggests that NUTM1 fusions may occur in an unknown number of aggressive thyroid carcinomas, possibly with distinctive histologic features but with thyrocyte differentiation. Recognition of this entity potentially has significant prognostic implications. Moreover, thyroid carcinomas with NUTM1 fusions may be amenable to treatment with NUT carcinoma-targeted therapy such as a bromodomain and extraterminal domain protein small molecular inhibitor (BETi).

Ovarian Primitive Neuroectodermal Tumor: Are You Central or Peripheral?

Primitive neuroectodermal tumors (PNETs) of the ovary are rare, highly aggressive neoplasms with fewer than 100 cases described. PNETs of the ovary can be classified as either peripheral or central types. The peripheral PNETs have small round cells with or without rosette formation, and the central PNETs can be further delineated based on the CNS tumor they morphologically resemble. We present a case of a central type ovarian PNET in a young female presenting with a pelvic mass and elevated serum tumor markers.

DEK-AFF2 Carcinoma of the Sinonasal Region and Skull Base: Detailed Clinicopathologic Characterization of a Distinctive Entity.

A novel DEK-AFF2 fusion was recently reported in 4 nonkeratinizing squamous cell carcinomas of the sinonasal region and skull base, including 1 with exceptional response to immunotherapy, but it is not yet clear if this rearrangement defines a unique clinicopathologic category or represents a rare event. This study aims to characterize a larger cohort of carcinomas with DEK-AFF2 fusions to assess whether they truly constitute a distinctive entity. Among 27 sinonasal and skull base nonkeratinizing squamous cell carcinoma that were negative for human papillomavirus and Epstein-Barr virus, RNA sequencing identified DEK-AFF2 fusions in 13 cases (48%). Nine were centered in the nasal cavity, 2 in the middle ear/temporal bone, 1 in the nasopharynx, and 1 in the orbit. These tumors displayed recurrent histologic features including (1) complex endophytic and exophytic, frequently papilloma-like growth, (2) transitional epithelium with eosinophilic to amphophilic cytoplasm, (3) absent or minimal keratinization with occasional compact keratin pearls, (4) monotonous nuclei, and (5) prominent tumor-infiltrating neutrophils or stromal lymphocytes. This appearance not only overlaps with high-grade basaloid sinonasal carcinomas but also with benign papillomas and tumors reported as low-grade papillary Schneiderian carcinoma. However, DEK-AFF2 carcinomas showed frequent local recurrence, cervical lymph node metastases, and distant metastasis with 2 deaths from disease, confirming they are aggressive malignancies despite relatively bland histology. Overall, the distinctive molecular, histologic, and clinical features of DEK-AFF2 carcinomas suggest they represent a unique entity in the sinonasal region. This tumor merits increased pathologic recognition to better understand its prognostic and therapeutic implications.

Unexpected arteriovenous malformation of the thyroid resulting in significant intraoperative blood loss.

A 49-year-old morbidly obese woman with metastatic endometrial carcinoma was referred for evaluation of an incidentally identified large right thyroid nodule found on computed tomography performed for cancer evaluation. Ultrasound revealed a 9.7 cm solid isoechoic homogeneous right thyroid nodule. Fine needle aspiration was benign. Given size, resection was recommended following completion of chemotherapy and radiation. At the time of right thyroid lobectomy, extremely large vessels were encountered, and the procedure was complicated by estimated blood loss of 2 L. Final pathology revealed a large, benign adenomatous nodule and vascular features consistent with arteriovenous malformation (AVM). Unlike previously reported cases, the diagnosis of a thyroid AVM was not known preoperatively.

A diagnostic review of carcinomas and sarcomas of the mediastinum: making the diagnosis on fine-needle aspiration and core needle biopsy specimens.

The mediastinum is a complex anatomic region that can pose many diagnostic challenges on fine-needle aspiration (FNA) and core needle biopsy (CNB). With the recent technological advancements in EBUS-TBNA and EUS-guided procedures, FNA/CNB is being increasingly utilized to obtain the initial and, in many cases, the only diagnosis. As a result, it is imperative to have an understanding of the pearls and pitfalls associated with both the more common and rarer malignancies that occur at this site. Although the vast majority of mediastinal malignancies encountered in routine clinical practice are metastatic carcinomas to mediastinal lymph nodes, primary tumors and tumors that directly extend into the mediastinum are also encountered. As always, a multimodal approach with clinical and radiographic correlation, a targeted IHC panel, and molecular testing when indicated are indisposable and necessary tools in the diagnostic workup of mediastinal malignancies. This review focuses on the salient diagnostic features of malignancies of epithelial and mesenchymal origin, excluding tumors of neurogenic, thymic, hematolymphoid, and germ cell origins, which are discussed in separate articles of this issue.

Immunohistochemical analysis of the Wnt/ß-catenin signaling pathway in pancreatic neuroendocrine neoplasms.

AIM: To investigate the role of the Wnt/ß-catenin pathway in pancreatic neuroendocrine neoplasms (PanNENs). METHODS: Tissue microarrays containing 88 PanNENs were immunohistochemically labeled with antibodies to ß-catenin, E-cadherin, adenomatous polyposis coli (APC), chromogranin and synaptophysin. One case had only metastatic tumors resected, whereas others (n = 87) received pancreatectomy with or without partial hepatectomy. Pathology slides, demographic, clinicopathologic, and follow up data were reviewed. Patients' demographics, clinicopathologic features, and immunohistochemical results from 87 primary tumors were compared between patients with low stage (stage I/II) and high stage (stage III/IV) tumors. In addition, correlation of immunohistochemical results from primary tumors with disease-specific survival (DSS) was evaluated. RESULTS: Strong membranous ß-catenin staining in the primary tumor was observed in all 13 stage III/IV PanNENs as compared to 47% (35/74) of stage I/II tumors (P < 0.01). However, the strong membranous ß-catenin staining was unassociated with tumor grade or DSS. Decreased membranous ß-catenin staining was associated with decreased membranous E-cadherin labeling. Nuclear ß-catenin staining was seen in 15% (2/13) of stage III/IV PanNENs as compared to 0% (0/74) of stage I/II tumors (P = 0.02). The case with metastasectomy only also showed nuclear ß-catenin staining. Two of the three cases with nuclear ß-catenin staining were familial adenomatous polyposis (FAP) patients. Lack of APC expression was seen in 70% (57/81) of the cases, including the 3 cases with nuclear ß-catenin staining. Expression of E-cadherin and APC in primary tumor was not correlated with tumor grade, tumor stage, or disease specific survival. CONCLUSION: The Wnt/ß-catenin pathway was altered in some PanNENs, but did not Impact DSS. PanNENs in FAP patients demonstrated nuclear ß-catenin accumulation and loss of APC.

Metastatic ductal carcinoma of the breast to the thyroid gland diagnosed with fine needle aspiration: A case report with emphasis on morphologic and immunophenotypic features.

Metastases to the thyroid are uncommon [<0.2% of thyroid fine needle aspirations (FNA)]. Of metastases to the thyroid, breast carcinoma is relatively common. The diagnosis of metastasis to the thyroid has important therapeutic and prognostic implications. To our knowledge, a morphologic and immunophenotypic comparison of metastatic ductal carcinoma of the breast and primary thyroid carcinomas has not been reported. Here, we report the case of a 37-year-old female with a history of metastatic ductal carcinoma of the breast (modified Bloom-Richardson grade 2; ER+, PgR+, HER2+) diagnosed 6 years prior. She developed hoarseness, prompting a CT scan. Multiple thyroid nodules were found, including a 1.5 cm hypoechoic, solid, irregularly-shaped nodule. On FNA, cells were arranged singly and in crowded groups, varied in size and degree of pleomorphism, and exhibited rare nuclear grooves, inconspicuous nucleoli, and rare intracytoplasmic lumina with no nuclear pseudoinclusions or colloid (Figs. 1A and B). These findings raised the differential of papillary thyroid carcinoma (Fig. 1C), follicular neoplasm (Fig. 1D), medullary carcinoma (Fig. 1E), parathyroid (Fig. 1F), and metastatic breast carcinoma. Immunostaining for GATA-3 (+), ER (+), PAX-8 (-), and TTF-1 (-) was consistent with metastatic breast carcinoma (Fig. 2). We conclude that metastatic breast carcinoma to the thyroid may morphologically mimic primary thyroid carcinoma on FNA; a panel of immunomarkers, such as GATA-3, hormonal marker(s), PAX-8, and TTF-1, may be useful in some cases. GATA-3 immunostaining for metastatic breast carcinoma was helpful in our case and has not been previously reported in a thyroid metastasis sampled by FNA. Diagn. Cytopathol. 2016;44:530-534. © 2016 Wiley Periodicals, Inc.

Differential expression of ribosomal proteins in myelodysplastic syndromes.

Aberrations of ribosomal biogenesis have been implicated in several congenital bone marrow failure syndromes, such as Diamond-Blackfan anaemia, Shwachman-Diamond syndrome and Dyskeratosis Congenita. Recent studies have identified haploinsufficiency of RPS14 in the acquired bone marrow disease isolated 5q minus syndrome, a subtype of myelodysplastic syndromes (MDS). However, the expression of various proteins comprising the ribosomal subunits and other proteins enzymatically involved in the synthesis of the ribosome has not been explored in non-5q minus MDS. Furthermore, differences in the effects of these expression alterations among myeloid, erythroid and megakaryocyte lineages have not been well elucidated. We examined the expression of several proteins related to ribosomal biogenesis in bone marrow biopsy specimens from patients with MDS (5q minus patients excluded) and controls with no known myeloid disease. Specifically, we found that there is overexpression of RPS24, DKC1 and SBDS in MDS. This overexpression is in contrast to the haploinsufficiency identified in the congenital bone marrow failure syndromes and in acquired 5q minus MDS. Potential mechanisms for these differences and aetiology for these findings in MDS are discussed.

Value of ultrasound guidance in cytopathologist-performed fine-needle aspirations of palpable lesions.

INTRODUCTION: Fine-needle aspirations (FNAs) of palpable masses are often performed by cytopathologists without ultrasound (US) guidance. Nonetheless, variations in the actual depth of palpable masses lead to occasional challenges. US guidance allows cytopathologists to visualize the mass and guide needle placement. This study retrospectively addressed the utility of US by comparing FNAs performed by cytopathologists on palpable masses with and without US guidance. MATERIALS AND METHODS: Cytopathologist-performed FNAs with and without US guidance from March 1, 2013 to July 1, 2014 were identified. The number of passes, location of lesions, and interpretations were recorded. Available slides were reviewed to determine the proportion of passes that contained diagnostic cellular material and cases in which diagnostic material was present on the first needle pass. RESULTS: In this study, 134 palpation-guided FNAs and 118 US-guided FNAs were analyzed. The percentage of nondiagnostic cases was significantly lower for US-guided FNAs (2.5%) than for palpation-guided FNAs (12.7%; P = 0.004). The average number of needle passes was significantly lower for US-guided FNAs (2.9) than for palpation-guided FNAs (3.6; P = 0.0002). Twenty-two of 118 of US-guided FNAs (18.6%) and 6 of 134 palpation-guided FNAs (4.5%) were completed after only a single pass (P = 0.0008). The percentage of passes with diagnostic material was significantly higher for US-guided FNAs (73.6% versus 60%; P = 0.0002). CONCLUSIONS: For palpable masses, US-guidance adds value to cytopathologists in obtaining diagnostic cellular material more often on the first pass and with fewer passes overall than by palpation alone. This has a potentially beneficial impact on patient care owing to the increased precision and accuracy of needle guidance with ultrasonography.