bluuebunny/crossref_metadata_2025 huggingface dataset:
The Utility of Ultrasound in the Diagnosis of “Cystic” Lesions of the Salivary Gland
Authors: Sayeed Sadia , Powers Celeste N.
Published: September 2023

Unlike in the thyroid, ultrasound (US) imaging of salivary gland lesions that show posterior enhancement or through transmission does not necessarily imply the presence of a cystic lesion. The 3 cases presented in this article illustrate the wide range of diagnoses that may have very similar findings by US imaging. Thus, emphasis is placed on the need for sampling of these lesions with careful evaluation of both US images and ideally US-guided fine-needle aspiration cytology to arrive at an accurate interpretation.
Lymph Node Fine-Needle Aspiration: 2 Cases Demonstrating Benefits of Ultrasound Guidance
Authors: Jug Rachel , Jiang Xiaoyin “Sara”
Published: September 2023

Pathologist performed fine-needle aspiration (FNA) biopsies yield high adequacy rates, result in effective triage of material for additional studies, and offer a minimally invasive method for tissue procurement. Ultrasound-guided FNA (US-FNA) expands the scope of pathologists' FNA capabilities allowing for deeper, nonpalpable lesions to be biopsied while avoiding crucial structures and enabling targeted biopsies of sonographically concerning regions. To illustrate the utility of US-FNA in clinical practice, we present 2 cases in which diagnostic material was obtained by pathologist-performed US-FNA from neck lymph nodes detected on positron emission tomography scans. The first was a 71-year-old woman with a history of both invasive lung and breast adenocarcinomas, and the second was a 60-year-old woman with a history of lower gastrointestinal tract squamous cell carcinoma. The lymph node biopsy from the first patient yielded adequate material to perform molecular diagnostic studies, detecting an activating KRAS mutation, providing additional prognostic and therapy guiding information. In the second case, ultrasound guidance allowed the pathologist to perform a biopsy on a nonpalpable lymph node and obtain a diagnosis from this minimally invasive procedure. Both lymph nodes featured characteristics indicative of involvement by metastatic carcinoma. Ultrasound examination can help characterize lesions, guiding cytopathologists to select an appropriate biopsy trajectory for optimal sampling.
Acid-Fast Bacteria in Disguise: Mycobacterium avium Complex in Purulent Exudate; Ultrasound Correlation
Authors: Kraft Adele , Wiles Austin , Doern Christopher
Published: September 2023

In immunocompetent hosts, Mycobacterium avium complex lymphadenitis is almost exclusively a disease of children, involving cervical lymph nodes. In the setting of human immunodeficiency virus infection, it can occur as a manifestation of the immune reconstitution inflammatory syndrome. This case study reports a case of M. avium complex in the setting of immune reconstitution inflammatory syndrome, presenting as purulent lymphadenitis, correlating cytopathology and surgical pathology findings with ultrasound imaging.
Benign Hepatic Lesions Arising in Accessory Hepatic Lobes
Authors: AlFarkh Wedad , Torbenson Michael S. , Mounajjed Taofic
Published: September 2023

An accessory hepatic lobe is an uncommon hepatic congenital anomaly that can sometimes mimic a mass lesion clinically and radiologically. Because accessory hepatic lobes are only rarely resected, detailed descriptions of their histologic features are sparse. We report the histologic and immunohistochemical features of 3 cases of resected accessory hepatic lobes, all of which contained benign hepatic lesions (2 hepatic adenomas [HAs] and 1 focal nodular hyperplasia). All accessory lobes were connected to the liver by a pedicle. Histologically, all lesions demonstrated no cytologic or architectural atypia. Based on immunohistochemical analysis, 1 HA was classified as inflammatory type (positive for C-reactive protein and serum amyloid A), and 1 was unclassified type (negative for C-reactive protein, serum amyloid A, glutamine synthetase, and β-catenin and positive for liver fatty acid–binding protein); the focal nodular hyperplasia showed the typical map-like staining pattern with glutamine synthetase. Interestingly, multiple foci of myelolipoma were identified within the unclassified-type HA. Of note, in all cases, the nonlesional hepatic parenchyma featured structural vascular abnormalities of the hepatic artery branches, including abnormal thickening of arterial branches and multiple arterial branches per single portal tract. Our findings describe, for the first time, benign hepatic lesions arising in accessory hepatic lobes and suggest that accessory lobes are perhaps prone to such benign lesions because of structural abnormalities in their vasculature.
A 64-Year-Old Woman With Posttransplant Hepatitis
Authors: Hardy Naomi , Twaddell William S.
Published: September 2023

Abnormal liver function tests and nonspecific histopathologic findings are relatively common in the post–liver transplant setting. Whereas some cases remain idiopathic and many resolve spontaneously, some carry a risk of chronicity and long-term liver dysfunction including cirrhosis, graft loss, and death. Accurate assessment and follow-up of such findings are therefore crucial in this population.

We report a case of a 64-year-old woman who underwent liver transplantation for chronic hepatitis C infection with cirrhosis. Several months after transplantation, she underwent a liver biopsy as part of a workup for abnormal serologic studies and transaminase elevation. The biopsy showed nonspecific hepatitis. Eventually, additional serologic testing demonstrated hepatitis E viral infection.

Causes of hepatitis and other forms of posttransplant liver disease, including hepatitis E, are discussed.
Liver Transplant in a 71-Year-Old Man With a Diagnosis of Nonalcoholic Steatohepatitis
Authors: Twaddell William S.
Published: September 2023

Fatty liver disease is an increasingly common indication for liver transplantation. Because of its prevalence, it may coexist with other causes of chronic liver disease, many of which may carry implications for treatment or follow-up of patients or their families. An increased degree of suspicion may be required to detect concurrent liver disease. We report a case of a 71-year-old man who underwent liver transplantation for nonalcoholic steatohepatitis. The explanted liver showed evidence of coexisting α1-antitrypsin deficiency disorder. The clinicopathologic features and epidemiology of fatty liver disease and α1-antitrypsin deficiency disorder are discussed, along with other possible coexisting disease.
Incidental Hepatic Granulomas in a Young Woman
Authors: Weidner Anna-Sophie
Published: September 2023

Hepatic granulomas are identified in approximately 3% to 4% of liver biopsies in the Western world. Their presence raises a broad differential diagnosis for the pathologist to consider, including infectious, immune-mediated, and drug-induced etiologies. Certain histologic features of granulomas and the adjacent liver parenchyma can help narrow the differential diagnosis, although clinical and laboratory correlation is often necessary to establish a definitive diagnosis. The purpose of this article is to review the morphologic classification of hepatic granulomas and to discuss hepatic sarcoidosis, one of the most common immune-mediated causes.
Histopathologic Approach to Cholestatic Diseases of the Liver
Authors: Jessurun Jose
Published: September 2023

Liver biopsy specimens of patients with cholestatic diseases pose a challenge to pathologists since, in most instances, this procedure is performed in a selected group of patients in whom clinical, laboratory, and imaging studies are inconclusive. Proper interpretation of the various histologic features is facilitated by the recognition of the most common patterns, which correlate with a defined group of diseases. Cholestatic disorders are grouped in 2 broad categories: acute and chronic. Four histologic patterns with different clinical implication are recognized within the first category: (1) ductular reaction, (2) pure canalicular cholestasis, (3) cholestasis with intrahepatic bile duct disease, and (4) cholestatic hepatitis. Chronic disorders are recognized by portal-based fibrosis, Mallory-Denk bodies, cholate stasis, accumulation of copper or copper-binding proteins, and biliary-type cirrhosis. Immunohistochemical reactions for cytokeratin 7 help to identify damaged bile ducts, highlight reactive ductules, and, most importantly, provide support for a cholestatic disorder by the staining of periportal hepatocytes (intermediate phenotype). The histologic features of primary biliary cholangitis and primary sclerosing cholangitis are reviewed with special emphasis on overlap syndromes and other entities that enter in the differential diagnosis.
Human Polyomavirus 7 and WU Polyomavirus-Associated Lymphocytic Bronchitis/Bronchiolitis in Native and Allograft Lung Biopsies From Immunocompromised Patients: Report of 3 Cases and Review of Literature
Authors: Mehrad Mitra , Trejo Bittar Humberto E. , Yousem Samuel A.
Published: September 2023

Human polyomavirus (PyV) family comprised 13 DNA viruses, which cause subclinical infection in more than 90% of the general population. However, significant disease including cancer is mainly observed in immunosuppressed patients. Few studies have investigated the detection of PyV in the respiratory tract. In this report, 3 transbronchial biopsies showed viral inclusions on histologic examination and were evaluated for anti-SV40 large T antigen (SV40 T Ag) by immunohistochemistry (IHC), in situ hybridization, and viral genome sequencing by polymerase chain reaction. Patients 1 and 2 were immunosuppressed lung transplant recipients. Patient 1 presented with diffuse pruritic rash and respiratory failure, and patient 2 with PyV viremia. Patient 3 had chronic lymphocytic leukemia/small lymphocytic lymphoma and presented with cough and shortness of breath. Histologic examination of all 3 lung biopsies were similar and revealed predominantly bronchial epithelial cells with enlarged nuclei, smudgy chromatin quality, and lymphocytic bronchitis/bronchiolitis with a patchy alveolar septal mononuclear infiltrate. SV40 large T antigen IHC was positive in all cases, whereas in situ hybridization for BK and JC virus was negative. Polymerase chain reaction sequencing identified PyV7 in case 1 and WUPyV in cases 2 and 3. We describe for the first time that PyV7 and WUPyV may be associated with lymphocytic bronchitis/bronchiolitis in the lungs of immunosuppressed individuals. It is important to be cognizant of the cross-reactivity of SV40 T Ag IHC with other types of PyV and equally essential to distinguish PyV bronchitis from other viral pathogens.
Phosphaturic Mesenchymal Tumor: A Single Case Report Discussing Diagnostic and Therapeutic Challenges of Tumor-Induced Osteomalacia
Authors: Homlar Kelly , Sullivan Brian T. , Sharma Suash
Published: September 2023

Phosphaturic mesenchymal tumor is a rare neoplasm that produces fibroblast growth factor 23 resulting in the paraneoplastic tumor-induced osteomalacia. Patients are typically diagnosed several years after the first signs of bone pain, fatigue, and weakness; the non-specific character of the symptoms often delays the diagnosis and curative surgical treatment. The following case report details a classic presentation of a phosphaturic mesenchymal tumor of mixed connective tissue type involving the right posterior tibialis muscle with erosion of the adjacent medial fibular cortex. The patient underwent a surgical resection and is currently asymptomatic. This report highlights the need for multidisciplinary diagnostic effort, effectiveness, of early surgical intervention, and emphasizes the importance of including this rare but damaging disease process in the differential diagnosis of osteomalacia.
Isolated Pulse Granuloma in a Mesenteric Lymph Node: Unusual Nodal Manifestation Associated With Crohn Disease Complicated by Ileal Adenocarcinoma
Authors: Medlicott Shaun A. C. , Eidus Leslie , Trpkov Kiril
Published: September 2023

Pulse granuloma is an unusual inflammatory reaction to legumes. Pulse granulomas of the gastrointestinal tract are typically accompanied by significant mural damage due to ulceration, fistula, or perforation. We describe a solitary pulse granuloma in a mesenteric lymph node of a 74-year-old male patient with Crohn disease, who presented with an ileal adenocarcinoma, but without demonstrable fistula or perforation. To our knowledge, this is only the second reported example of Crohn disease associated with a pulse granuloma in a mesenteric node and also only the second example of a nodal location for any documented pulse granuloma. We postulate that mesenteric lymph node pulse granuloma may represent a unique and unusual type of morphology associated with Crohn disease.
Brown Bowel Syndrome Presenting as a Small Bowel Obstruction
Authors: Alwatari Yahya , Preciado Christopher , Tondon Rashmi , Shiroff Adam
Published: September 2023

Brown bowel syndrome (BBS) is a rare condition characterized by lipofuscin deposition in the muscularis propria of the bowel. It is associated with vitamin E deficiency and malabsorptive syndromes. We report a case of BBS in a patient with previously undiagnosed primary intestinal lymphangiectasia. The patient had a longstanding history of malnutrition as well as bilateral lower extremity lymphedema and chylous ascites. He presented to our hospital with small bowel obstruction (SBO). Initial magnetic resonance enterography revealed a dilated duodenum, which when biopsied revealed only lymphangiectasia and lymphedema. He was managed conservatively and discharged following resolution of the obstruction. The patient presented again 1 month later with SBO that failed to resolve with conservative treatment. Subsequent exploratory laparotomy discovered a portion of pale, edematous, aperistaltic jejunum. The specimen was resected, and pathologic examination revealed brown granular pigment deposition within the muscularis propria, which was highlighted by periodic acid–Schiff and lipofuscin stains, diagnostic of BBS. Nutritional workup revealed multiple deficiencies. The patient's clinical findings and history were suggestive of primary intestinal lymphangiectasia with resulting nutritional deficiencies leading to BBS. Outpatient follow-up after recovery revealed an elevated 24-hour fecal α1 antitrypsin, which supports this diagnosis. The patient has since improved following adherence to a low-fat diet. The combined clinical, radiographic, and pathologic findings in this case allowed for the resolution of this complex diagnostic dilemma. Although rare, BBS remains an important consideration in the differential diagnosis of a patient with SBO and history of chylous ascites and should be viewed as a symptom of underlying treatable nutritional deficiency.
Poorly Differentiated/Anaplastic Chordoma in a Child—Case Report and Review of the Literature
Authors: Morbeck Diogo Lago , Batista Patricia Marquis Dornelas , Tregnago Aline Caldart , Cabrera Rafael Adame , Costa Felipe D’Almeida , Kalil Ricardo Karam
Published: September 2023

Chordomas are rare bone tumors, with highest incidence after the age of 40 years. When they occur in infants and toddlers, they usually are poorly differentiated/anaplastic chordomas with characteristic histopathologic presentation and unique molecular changes such as the lack of expression of SMARCB1/INI1. We present the case of a 3-year-old girl with a 5.0-cm sacrococcygeal mass. Magnetic resonance imaging showed a lobulated, heterogeneous mass attached to S5. Chordomas are very rare at this age; therefore, it is very important to distinguish this tumor from other more common neoplasms that occur in this location and age range because when they are identified their immunogenetic profile may suggest a worse prognosis. Histological, immunohistochemical, molecular characteristics, and differential diagnosis of this variant of chordoma are discussed.
Primary Renal Well-differentiated Neuroendocrine Tumor—Report of a Case With Cytological-Histopathologic Correlation and Review of Literature
Authors: Manucha Varsha , Azar Azniv , Roda Manohar , Lewin Jack
Published: September 2023

Renal well-differentiated neuroendocrine tumor (WDNET; also known as carcinoid), although considered as a distinct entity in the World Health Organization classification, continues to be an enigma to the pathologists and clinicians because of its rarity. In this case report, we describe a case of primary renal WDNET in a 54-year-old man. The tumor was initially diagnosed as a urothelial carcinoma. After a second review and a broad-spectrum immunopanel, a revised diagnosis of WDNET was rendered.
Expanding the Spectrum of Ciliated Muconodular Papillary Tumor of the Lung: A Case Showing Nonpapillary and Purely Glandular Morphology
Authors: Baratelli Felicita , Wei Christina , Elatre Wafaa , Xiao Guang-Qian , Ward Pamela , Pettersson Jonas , Campan Mihaela , Larsen Brandon T. , Ashley Prosper , Wang Linan , Cohen Robbin , Koss Michael
Published: September 2023

We report an unusual case of a subpleural bronchiolar/glandular proliferation in a 76-year-old Hispanic woman with microscopic features reminiscent of those of the so-called ciliated muconodular papillary tumor (CMPT). The lesion presented radiologically as a solitary subpleural nodule measuring 2.7 × 1.2 cm with low standard uptake value (SUV) of 1.4. Microscopically, it was circumscribed but unencaspulated and consisted of mucous-filled spaces lined by cytologically bland cuboidal to low columnar cells, including goblet cells and ciliated epithelium, with underlying nodular collections of basaloid cells. The lining cells stained diffusely for CK7 but only focally for TTF-1 and CEA, whereas the basal cells expressed CK5/6. Ki-67 showed a proliferative index of less than 1%. Target gene mutation analysis with a 50-cancer-related-gene panel using next-generation sequencing showed the bronchiolar proliferation to harbor an EGFR in frame exon 20 insertion mutation with 30% allele frequency, which supports a neoplastic diagnosis. Accordingly, given the mutually exclusive nature of driver mutations, a BRAF V600E mutation was absent by both immunohistochemical and next-generation sequencing analysis. Microscopic evidence of metastatic spread was not seen in 8 regional lymph nodes examined. Given the histomorphology and immunohistochemical findings, the mutational profile and the reported heterogeneous microscopic patterns of CMPTs, including glandular component, we suggest the tumor herein described be a glandular variant of CMPT. We therefore suggest that the term ciliated muconodular tumor may be more appropriate for this group of lesions.
Case Report: Benign Phyllodes Tumor of the Vulva
Authors: Vella Josefa E.O. , Thomas Michael P. , Singh Ruchira , Shaaban Abeer M.
Published: September 2023

Phyllodes tumor of the vulva is a rare tumor and is histologically similar to phyllodes tumor of the breast. Morphological and immunohistochemical features of a case are presented here.
RET/PTC1 Rearrangement in Hashimoto Thyroiditis: Canonical WNT Expression Up-regulation for Neoplastic Promotion
Authors: Al-Hashimi Fatima , Diaz-Cano Salvador J.
Published: September 2023

Background

More than half a century has passed since the association between papillary thyroid carcinoma (PTC), and Hashimoto thyroiditis (HT) has been described. The discovery of the RET/PTC oncogene 30 years later has further strengthened this argument, followed by the associations made between hyalinizing trabecular adenoma (HTA) and both PTC and HT. Numerous researchers studied these relationships, with some debating a valid link.

Findings

This case of a 28-year-old woman with HT-associated PTC and a coexisting HTA offers a unique opportunity to study these three lesions together in the same microenvironment. Fresh tissue analysis for gene expression showed that all three expressed RET/PTC1 transcripts, whereas this was not seen in the control normal thyroid tissue. There was also an increased expression of AKT, ERK1, nuclear β-catenin, and TCF4 in both the HTA and PTC sampled tissue. AKT plays a central role in regulating cell proliferation and survival by inhibiting apoptotic processes, whereas ERK1 leads to cell proliferation. Both β-catenin and TCF4 are linked to the canonical WNT/β-catenin pathway.

Conclusions

The expression of RET/PTC1 highlights the link between inflammatory processes such as HT and neoplastic conditions such as HTA and PTC. The limited expression of TCF4, AKT, ERK1, and β-catenin supports the notion that the canonical WNT/β-catenin pathway plays a pivotal role in the development of this neoplasm. It is important to note that at this time, gene expression alone is not sufficient to make a distinction between benign and malignant thyroid lesions.
Role of Dynamic Markers in the Molecular Testing of Indeterminate Thyroid Nodules
Authors: Banizs Anna B. , Toney Nicole A. , Jackson Sara A. , Narick Christina M. , Silverman Jan F. , Finkelstein Sydney D.
Published: September 2023

Molecular testing of fine-needle aspirates of indeterminate thyroid nodules is now standard and consists mainly of mutational analysis of the most frequent point mutations and chromosomal rearrangements occurring in advanced thyroid tumors with the goal of determining these genetic alterations early in the neoplastic process. However, mutation panels, even extended ones, face challenges; namely, genetic alterations in cytologically indeterminate categories are represented at relatively low percentage, and with the exception of strong driver mutations, the mere presence of a mutation does not reliably predict malignancy.

Currently, dynamic markers such as microRNAs (miRNAs) are being explored to overcome the limitations of mutational panels. Various stages of neoplasia are associated with characteristic patterns of deregulated miRNAs, making them attractive candidates as predictive markers. In this review, we summarize current knowledge from the literature about the potential role of miRNAs in risk stratification of indeterminate thyroid nodules, including our findings based on a large molecular database of fine-needle thyroid aspirates. We believe miRNA classifiers and mutational analysis in combination are powerful tools in the risk stratification of indeterminate thyroid nodules.
Cytology Slides for Molecular Analysis Can Address Both Interobserver Variability and Sample Heterogeneity: Overview of Thyroid Molecular Testing
Authors: Narick Christina M. , Toney Nicole A. , Kumar Gyanendra , Finkelstein Sydney D.
Published: September 2023

Studies have shown that a high degree of inter and intraobserver variability, in addition to the heterogeneity of the sample itself, can inhibit the accuracy of cytopathological assessment of thyroid nodules. Guidelines have recommended the use of molecular analysis, used in conjunction with cytology, to assist in the guidance of patient management. Currently, there are several commercially available molecular tests offered to better assess overall malignancy risk, each now with updated and expanded capability. The collaboration between molecular pathology and cytopathology is critical to better understand the biology of these lesions and help clinicians optimize patient management and surgical decisions.
Sarcomatoid Hepatocellular Carcinoma: A Case Report and Review of the Differential Diagnosis of Malignant Spindle Cell Lesions of the Liver
Authors: Stashek Kristen M. , White Rachel , Song Linda , Tondon Rashmi , Kallen Michael , Twaddell William
Published: September 2023

Sarcomatoid hepatocellular carcinoma is a rare aggressive variant of hepatocellular carcinoma that typically shows a conventional component of hepatocellular carcinoma admixed with a malignant spindle cell proliferation. In small biopsy specimens, the conventional component may not always be present; therefore, knowledge of the differential diagnosis of malignant spindle cell lesion presenting in the liver is necessary to ensure accurate diagnosis.
Incidental Collision Tumor: Two Common Metastases Meet in the Neck
Authors: Kallen Michael E. , White Rachel , Hittman Jamie , Hatten Kyle M. , Stashek Kristen M. , Staats Paul N. , Papadimitriou John C.
Published: September 2023

Human papillomavirus (HPV)–positive oropharyngeal squamous cell carcinoma is a biologically and clinically distinct type of head and neck cancer, featuring a generally improved prognosis over its HPV-negative counterparts. Papillary thyroid carcinoma is the most common thyroid malignancy and has a high frequency of regional lymph node metastasis and generally indolent clinical behavior. We present a case of intranodal collision between HPV-positive oropharyngeal squamous cell carcinoma and incidental papillary thyroid carcinoma. These two common lesions of the head and neck highlight an emergent area of complicated histology and raise interesting questions about tumor biology. We briefly review the variations of composite lesions described in the head and neck, as well as the potential prognostic implications between different types and role of ancillary testing and molecular diagnostics in their separation.
Aggressive Variants of Follicular- and Parafollicular-Derived Thyroid Carcinoma
Authors: Rossi Esther Diana , Faquin William C. , Pantanowitz Liron
Published: September 2023

There are several aggressive variants of thyroid carcinoma including those of papillary thyroid carcinoma, poorly differentiated thyroid carcinoma, anaplastic thyroid carcinoma, and medullary thyroid carcinoma that are important to recognize. Among thyroid malignancies, papillary thyroid carcinoma represents the most common form of endocrine cancer. Papillary thyroid carcinoma usually presents as an indolent cancer with high overall survival rates approaching 96%. However, a minority of thyroid carcinomas with distinctive histopathology (eg, tall cell, columnar cell, solid, hobnail, diffuse sclerosing, and diffuse follicular variant) behaves more aggressively and may not respond to routine treatment, leading to higher mortality. Other aggressive follicular-derived thyroid malignancies are represented by poorly differentiated thyroid carcinoma and anaplastic thyroid carcinoma, which are associated with an especially unfavorable prognosis. The most important aggressive parafollicular thyroid malignancy encountered is medullary thyroid carcinoma. This review describes the clinical, pathological, and molecular findings for these aggressive thyroid malignancies and underscores current concepts and controversies related to these tumors.
Histopathology of Encapsulated Follicular-Patterned Thyroid Tumors
Authors: Elsheikh Tarik M.
Published: September 2023

Encapsulated follicular-patterned thyroid tumors remain diagnostically challenging for pathologists, including experts. The differential diagnosis typically includes hyperplastic/adenomatous nodule, follicular adenoma, follicular thyroid carcinoma, and follicular variant of papillary thyroid carcinoma (FVPTC). Noninvasive follicular thyroid neoplasm with papillary-like features is a new terminology that was recently proposed for a subset of noninvasive FVPTC that has a highly favorable outcome and can be treated in a conservative manner. This is in contrast to invasive-encapsulated FVPTC that clinically behaves similar to follicular thyroid carcinoma and infiltrative FVPTC that behaves like classic PTC. In this review, the differential diagnosis of encapsulated follicular-patterned thyroid neoplasms is discussed, including noninvasive follicular thyroid neoplasm with papillary-like features and its recently revised pathologic criteria. Commonly encountered diagnostic challenges and pitfalls are also reviewed, including criteria for capsular and vascular invasion and minimal diagnostic features of papillary thyroid carcinoma.
Molecular Profiling of Unusual Thyroid Neoplasms
Authors: Goel Kanika , Finkelstein Sydney D. , Narick Christina M. , Silverman Jan F.
Published: September 2023

Thyroid neoplasms comprise a heterogeneous group of tumors, arising most commonly from follicular cells. While some neoplasms such as the papillary thyroid carcinoma have been widely studied and reported in the literature, our knowledge of the less common entities, including anaplastic thyroid carcinoma and medullary thyroid carcinoma is still deficient. In the current medical era, molecular characteristics of the tumors are being increasingly evaluated for their potential role in establishing diagnosis and to guide management. In this review article, we discuss some of the less common thyroid neoplastic entities, with a special focus on their molecular profiles. In addition, we share our own institutional experience obtained from molecular profiling of anaplastic thyroid carcinoma and medullary thyroid carcinoma.
Primary Thyroid Squamous Cell Carcinoma With Complete Response to Radical Surgery and Concurrent Chemoradiotherapy: Diagnostic Pathologic Workup and Clinical Management
Authors: Elsheikh Tarik M. , Adelstein David J. , Koyfman Shlomo A.
Published: September 2023

Primary squamous cell carcinoma (SqCC) of the thyroid gland is an extremely rare, highly aggressive malignancy associated with locally advanced disease and frequent metastases to regional lymph nodes and distant sites. There are no standardized guidelines for treating primary thyroid SqCC because of its rarity, but some investigators have recommended staging and treating it as a variant of anaplastic thyroid carcinoma. Prognosis, however, remains poor with minimal response to treatment and an estimated median survival of 6 to 14 months. We report a case of primary SqCC of the thyroid that was successfully treated with aggressive locoregional resection followed by concurrent radical dose radiotherapy and cisplatin-based chemotherapy. The patient remains free of disease more than 4 years after surgery and adjuvant chemoradiation. Because of potential prognostic and management implications, it is crucial to make an accurate pathologic diagnosis of primary SqCC of the thyroid and distinguish it from metastatic squamous carcinoma and other primary thyroid malignancies with squamous features. A thorough clinicopathologic diagnostic workup including immunohistochemistry, computed tomography scan, and endoscopy is mandatory. In this case, treatment similar to the standard management used for patients with locally advanced mucosal head and neck squamous cancer led to a successful outcome.
The Molecular Pathology of Appendiceal Neoplasms
Authors: Leeming Amy , Worrall David , Arends Mark Johan
Published: September 2023

We review the molecular pathological changes of appendiceal neoplasms, in part using the consensus terminology agreed by the Peritoneal Surface Oncology Group International (Am J Surg Pathol 2016;40(1):14–26; Histopathology 2017;71(6):847–858), with appendiceal neoplasms subcategorized as hyperplastic polyps and serrated lesions (with and without dysplasia), appendiceal mucinous neoplasms (low and high grade), adenocarcinoma, goblet cell tumors, and neuroendocrine neoplasms.
The Enigma of Goblet Cell Tumors of the Appendix
Authors: van Velthuysen Marie-Louise F. , van Eeden Susanne , Carr Norman J.
Published: September 2023

The term goblet cell carcinoid was first proposed in 1974 by Subbuswamy et al for a rare tumor of the appendix. Since then, it has been debated whether these tumors should be regarded as adenocarcinomas or as neuroendocrine tumors. Research on these neoplasms has been hampered by their rarity and the low density of tumor cells. However, their particular morphology legitimates their classification as an entity specific for the appendix. In this review the morphology, immunohistochemical profile and differential diagnosis are discussed. Recent literature on grading and molecular profiling is reviewed. These data show that grading these tumors using their morphologic growth patterns is of prognostic value. At the molecular level, goblet cell tumors differ from other appendiceal neoplasms, colon carcinoma, and neuroendocrine tumors and share similarities with other neoplasms such as diffuse-type gastric carcinoma. Goblet cell carcinomas thus emerge as an interesting target in this era of genetic profiling.
Eosinophilic Esophagitis
Authors: Chandan Vishal S. , Wu Tsung-Teh
Published: September 2023

Eosinophilic esophagitis is an immune-mediated chronic disease of the esophagus. It is clinically characterized by symptoms related to esophageal dysfunction and histologically by eosinophil-rich inflammation with a peak intraepithelial eosinophil count of at least 15 eosinophils per high-power field. Both children and adults can be affected with a strong male predominance. Food appears to be the key trigger, although the exact mechanisms remain unclear. Treatment for eosinophilic esophagitis can be summarized as the 3 D's: dietary, drugs, and dilatation. The differential diagnosis includes gastroesophageal reflux disease, eosinophilic gastroenteritis, drug hypersensitivity, hypereosinophilic syndrome, infection, Crohn disease, connective tissue diseases, and vasculitis.
High-Grade Serous Carcinoma Arising in Retroperitoneal Endosalpingiosis: A Case Report and Brief Review of Peritoneal Serous Metaplasia and Neoplasia
Authors: Richards Stephanie M. , Goel Rinal C. , Staats Paul N.
Published: September 2023

The peritoneum has a close relationship with the epithelium of the fallopian tube and ovarian surface and can thus undergo similar metaplastic and neoplastic processes, including the full spectrum of gynecologic serous neoplasia. We report a case of high-grade serous carcinoma arising in retroperitoneal endosalpingiosis in a patient with a history of ovarian high-grade serous carcinoma, followed by a brief review of peritoneal serous metaplasia and neoplasia.
Desmoplastic Small Round Cell Tumor: The Value of Cytology, Immunohistochemistry, and Molecular Features in the Diagnosis of This Challenging Diagnostic Entity
Authors: Bernieh Anas , Joyner David , Saad Ali G.
Published: September 2023

Desmoplastic small round cell tumor is a rare malignant neoplasm that usually occurs in adolescents and young adult males and typically presents as a large, often multinodular, intra-abdominal mass. The peritoneal cavity is the most common location of the tumor with multiple satellite nodules often noted at presentation. Extra-abdominal locations, such as the lung, kidney, middle ear, stomach, pancreas, pleura, bone, and the central nervous system, have been described. Distant metastases commonly involve the lymph nodes, liver, and lungs. Desmoplastic small round cell tumor is relatively rare, and only few cytologic descriptions are available. We present the case of a 16-year-old boy with unusually rapidly fatal desmoplastic small round cell tumor of the peritoneum with emphasis on the cytologic features. Recent advances in imaging techniques have resulted in increased number of cytologic preparations from unusual tumors or tumors in unusual locations. Morphologically, these tumors often display a divergent phenotype and immunophenotype. Immunohistochemistry plays a pivotal role in the characterization of these tumors and discrimination from other mimickers, particularly other “blue cell tumors.” Once suspected, identification of the characteristic translocation in these tumors confirms the diagnosis. Therefore, awareness of the cytologic features and the divergence of the immunophenotype of this tumor are crucial in order to arrive to the correct diagnosis and to ensure proper management plans of these often difficult-to-treat tumors.
Iron-associated Colitis: A Common Entity in an Uncommon Location
Authors: Reid Whitney L. , Cox Jesse L. , Livingston William C. , Talmon Geoffrey A.
Published: September 2023

Iron-induced mucosal damage is a common finding within the upper gastrointestinal tract. Because of physiologic factors, however, high concentrations of iron rarely reach the distal gastrointestinal tract, thus injury there has not been reported. Here, we present a case in which multiple factors contributed to iron-induced injury in the colon.
Adenosquamous Carcinoma Involving the Gastroesophageal Junction in a 71-Year-Old Man
Authors: Twaddell William Sanderson
Published: September 2023

Adenosquamous carcinoma (ASC) of the esophagus is an uncommon primary esophageal malignancy of uncertain pathogenesis, with several challenges complicating the establishment of a correct diagnosis. Neither the natural history nor the prognostic and therapeutic implications are well understood for this tumor. We report a case of a 71-year-old man who was found to have an ASC at the gastrointestinal junction. The clinicopathologic features as well as what is known of the epidemiology, pathogenesis, and prognosis and treatment of ASC are discussed, along with other possible coexisting disease.
Autoimmune Gastritis: An Underappreciated Entity
Authors: Matsukuma Karen , Torbenson Michael
Published: September 2023

Autoimmune gastritis is a relatively common but likely underdiagnosed form of chronic gastritis that is associated with iron-deficiency anemia as well as vitamin B12/cobalamin deficiency. This disease confers a 13-fold increased risk of gastric well-differentiated neuroendocrine tumors, due to persistently elevated gastrin levels, and a 3- to 7-fold increased risk of gastric adenocarcinoma. The case described here has a typical presentation of the disease, and the following review highlights key histologic features that aid in the identification of this inflammatory process. Additionally, background information on ancillary testing and mechanisms of disease are discussed with a focus on details most useful for the pathologist who is presented with the opportunity to make this often unexpected but medically significant diagnosis.
Squamous Cell Carcinoma With a Focal Neuroendocrine Carcinoma Component at the Esophagogastric Junction
Authors: Inomoto Chie , Kondo Yusuke , Hirabayashi Kenichi , Kumaki Nobue , Hatanaka Kazuhito , Tajiri Takuma , Nakamura Naoya
Published: September 2023

A 60-year-old woman presented to our hospital with a 1-month history of dysphagia. She smoked and consumed alcohol but had no notable past medical history. Physical examination revealed epigastric tenderness, and abdominal computed tomography revealed diffuse thickening of the esophageal wall and stenosis of the esophageal lumen. She underwent a barium-swallowing examination. A tumor that measured approximately 4 cm in length was detected with ulceration and stenosis in the distal esophagus and gastroesophageal junction. Tumor biopsy showed squamous cell carcinoma. Esophagectomy was performed. The pathological diagnosis was squamous cell carcinoma with a neuroendocrine carcinoma component; the latter component made up less than 30% of the lesion. Regional lymph node metastasis, consisting of squamous cell carcinoma and neuroendocrine carcinoma components, was also observed. The patient was diagnosed with multiple liver metastases 2 months postesophagectomy. She died 11 months after the surgery. Here, we present the above case and a review of relevant literature.
HER2 Testing in Gastric and Gastroesophageal Adenocarcinoma—Review and Update
Authors: Koro Konstantin , Swanson Paul E. , Yeh Matthew M.
Published: September 2023

Adenocarcinomas of the stomach and gastroesophageal junction are commonly encountered by practicing pathologists. In cases of advanced unresectable or metastatic disease, a patient may be a candidate for anti–human epidermal growth factor receptor 2 (HER2) targeted therapy. Eligibility for anti-HER2 therapy is determined by the pathologist, following an algorithm utilizing HER2 immunohistochemistry alone or in combination with chromogenic or fluorescence in situ hybridization. HER2 immunohistochemistry is interpreted using 4-tier scoring criteria that were devised and validated specifically for gastric adenocarcinomas. Here, current guidelines for utilization and interpretation of HER2 immunohistochemistry and in situ hybridization are reviewed. Also included is a discussion of some of the interpretation difficulties and pitfalls that may be encountered in routine pathology practice.
Transformed Mycosis Fungoides and Mimics: Exploring the Landscape of CD30+ Cutaneous T-Cell Lymphomas
Authors: Merechi Fikru , Koka Rima , Singh Zeba , Lee Seung Tae , Kallen Michael E.
Published: September 2023

Mycosis fungoides (MF) is an epidermotropic, primary cutaneous T-cell lymphoma (CTCL) with a generally indolent clinical course, although higher stage and transformed tumors can behave more aggressively. Large cell transformation may demonstrate CD30 expression and histologically resemble other CD30+ CTCLs, including lymphomatoid papulomatosis and cutaneous anaplastic large cell lymphoma. These entities are thought to exist on a spectrum with overlapping histologic features; however, it is of clinical importance that we do our best to accurately classify these entities due to the variability in treatment and prognosis. In this report, we present a case of CD30+ transformed MF and discuss the clues that allow us to make the challenging distinction between transformed MF and other CD30+ CTCLs. We review histologic and clinical features of these different disorders, with a focus on the revised World Health Organization classification of primary cutaneous lymphomas.
Transformation of Monoclonal B Lymphocytosis to Epstein-Barr Virus–Positive Large B-Cell Lymphoma With Intermediate Features Between Diffuse Large B-cell Lymphoma and Classic Hodgkin Lymphoma
Authors: Liu Ying , Ho Caleb , Roshal Mikhail , Baik Jeeyeon , Arcila Maria , Zhang Yanming , Dogan Ahmet , Xiao Wenbin
Published: September 2023

Transformation of chronic lymphocytic leukemia (CLL) to an aggressive lymphoma, so-called Richter syndrome, usually includes diffuse large B-cell lymphoma and classic Hodgkin lymphoma. The transformation can be clonally related to the underlying CLL and is often Epstein-Barr virus (EBV) associated. Here we report the case of an 86-year-old woman with a newly identified CLL-like monoclonal B-lymphocytosis who developed diffuse lymphadenopathy. Biopsy of the left axillary lymph node showed EBV-positive large B-cell lymphoma with morphologic and immunophenotypic features intermediate between diffuse large B-cell lymphoma and classic Hodgkin lymphoma, so-called gray zone lymphoma. Comprehensive immunophenotypic, cytogenetic, and molecular studies demonstrate a clonal relatedness that suggests a transformation from monoclonal B-lymphocytosis to EBV+ gray zone lymphoma.
Lymphoblastic Transformation of Follicular Lymphoma: A Case Report and Review of the Literature
Authors: Rosser Julie A. , Thomas Cody A.
Published: September 2023

Follicular lymphoma (FL) is one of the most common B-cell non-Hodgkin lymphomas in adults in the Western world. Prognosis is correlated with the clinical stage and histologic grade and, increasingly, the tumor genetic profile. A subset of patients with FL experiences histologic disease progression (ie, histologic transformation), of which the majority will demonstrate diffuse large B-cell lymphoma. We describe a patient initially diagnosed with low-grade FL with relapsed disease presenting as acute renal failure due to diffuse abdominal lymphadenopathy. Excisional biopsy of an inguinal lymph node at relapse showed high-grade areas with sheets of immature-appearing lymphoid cells adjacent to nodular areas characteristic of low-grade FL. Cells of both components were positive for BCL2 and CD19. The cells of the high-grade component were positive for CD99 and TdT and negative for CD20, whereas cells of the low-grade component were positive for CD20 and negative for CD99 and TdT. Fluorescence in situ hybridization studies demonstrated the IGH/BCL2 rearrangement in addition to an MYC rearrangement in both low- and high-grade components.
B-Lymphoid Blast Phase of Chronic Myeloid Leukemia: A Case Report and Review of the Literature
Authors: Ware Alisha D. , Wake Laura , Brown Patrick , Webster Jonathan A. , Smith B. Douglas , Duffield Amy S.
Published: September 2023

Chronic myeloid leukemia (CML) is a clonal hematopoietic stem cell disorder characterized by a reciprocal translocation, t(9;22)(q34.1;q11.2). This leads to fusion of the BCR and ABL1 genes, encoding an active tyrosine kinase that causes unregulated proliferation of the myeloid lineage. The BCR/ABL1 fusion protein is found not only in CML, but also in a subset of de novo B-lymphoblastic leukemia (B-LL). However, the fusion protein in CML is characteristically the slightly longer p210 variant, whereas the p190 variant is more frequently found in B-LL. Without treatment, CML will progress to accelerated and/or blast phase (BP). Disease progression is often characterized by accumulation of additional chromosomal abnormalities. The development of tyrosine kinase inhibitor (TKI) therapy that targets BCR/ABL1 has revolutionized treatment of CML and vastly improved outcomes, although the disease can still progress despite TKI therapy. Blast phase most commonly manifests as myeloid BP; however, up to 30% of BP presents as lymphoid BP (LBP), typically of the B-cell lineage. The B-lymphoblasts of LBP have a phenotype indistinguishable from that of de novo B-LL. However, LBP typically carries the p210 BCR/ABL transcript and may show distinct chromosomal anomalies, including loss of chromosome 9p. The prognosis for CML-BP is poor, although survival has improved with TKI therapy and stem cell transplant, and LBP has been associated with superior survival compared with myeloid BP. Here we present a case of CML in B-lymphoid BP and review the current literature.
Posttransplant Classic Hodgkin Lymphoma: Richter Transformation or Posttransplant Lymphoproliferative Disorder?
Authors: Lee Ina , Zou Ying , Hodges Susan , Rapoport Aaron P. , Hardy Nancy , Singh Zeba
Published: September 2023

Richter transformation (RT) is defined as the transformation of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) into high-grade lymphoma. An average of 5% of patients with CLL/SLL will have disease that undergoes RT during their clinical course. While most (75%) of these transformed cases manifest as diffuse large B-cell lymphoma, other variants occur, including a small minority (0.4%–0.7%) that progress to a classic Hodgkin lymphoma variant. Richter transformation portends a poor outcome in comparison to nontransformed CLL/SLL. Allogeneic stem cell transplantation (allo-SCT) can be offered, with a 5-year survival rate of 50% to 70%. In addition to disease relapse, transplantation carries significant risk of nonrelapse morbidity, including posttransplant lymphoproliferative disorder (PTLD). The distinction between disease progression or recurrence and PTLD can be challenging and has critical prognostic and therapeutic implications. In this report, we describe a patient whose initial CLL/SLL transformed to diffuse large B-cell lymphoma, who then received allo-SCT. Subsequent development of classic Hodgkin lymphoma proved to be a diagnostic conundrum, for which PTLD and disease progression/recurrence were both reasonable considerations. This case illustrates the diagnostic dilemma and semantic confusion faced by both pathologists and clinicians when lymphoproliferative disorders emerge within the immunologically complex interface of CLL/SLL, RT, and allo-SCT. As molecular technologies are becoming more commonplace in routine diagnostics, subpopulation clonal analysis may be useful in such cases. It may also be worth reevaluating the classification and criteria for PTLD and different subtypes of RT, especially in light of implications for prognosis and optimal therapies.