Common Diagnostic Challenges in Genitourinary Mesenchymal Tumors: A Practical Approach

Mesenchymal neoplasms within the genitourinary tract include a wide spectrum of tumors, ranging from benign to malignant, and tumors of uncertain malignant potential. Except for stromal tumors of the prostate, which originate from the specific prostatic stroma, these neoplasms generally resemble their counterparts in other body sites. The rarity of these neoplasms and the limitation associated with small biopsy samples present unique diagnostic challenges for pathologists. Accurate diagnosis is paramount, as it significantly influences prognosis and guides management and treatment strategies. This review addresses common diagnostic scenarios, discusses key differential diagnoses, and sheds light on potential diagnostic pitfalls

Follicular neoplasms with nuclear atypia versus other types of atypia: Should follicular neoplasms be stratified according to the presence of nuclear atypia?

Abstract Background The third edition of The Bethesda System (TBS) subclassifies the atypia of undetermined significance (AUS) category on the basis of the presence of nuclear atypia (AUS‐Nuclear). This approach is supported by studies showing significant differences in the risk of malignancy (ROM) between AUS‐Nuclear and those without (AUS‐Other). Although aspirates of follicular neoplasms (FNs) are characterized by marked architectural atypia, TBS recognizes the infrequent occurrence of FNs with mild nuclear atypia (FN‐Nuclear). Furthermore, limited studies have shown significant differences in ROM between FN‐Nuclear and those without (FN‐Other). This study explored potential differences in ROM, molecular‐derived risk of malignancy (MDROM), and molecular alterations between FN‐Nuclear and FN‐Other. Methods A retrospective database search identified 93 FN aspirates. Cytology slides, molecular reports, and histologic follow‐ups were reviewed. Both groups' benign call rate (BCR), positive call rate (PCR), MDROM, and ROM were computed and compared. Results Eighty‐six percent of aspirates (80 of 93) comprised FN‐Other, whereas 14% (13 of 93) were FN‐Nuclear. The BCR and PCR for FN‐Other were 51% and 49%, respectively. In contrast, they were 23% and 77% for FN‐Nuclear, respectively. The MDROM significantly differed between FN‐Other (30%) and FN‐Nuclear (56%) ( p  < .05). HRAS mutation was the most common molecular alteration in FN‐Nuclear, whereas mutations in NRAS / KRAS and copy number alterations were more common in FN‐Other. The ROM1/ROM2 in FN‐Other and FN‐Nuclear were 16%/31% and 54%/88%, respectively. Conclusions These results reveal that FN‐Nuclear exhibits significantly higher MDROM and ROM than FN‐Other, which provides support for a subclassification scheme for FNs based on the presence of nuclear atypia. Follicular neoplasm with nuclear atypia exhibits significantly higher risk of malignancy and molecular‐derived risk of malignancy than follicular neoplasm without nuclear atypia, which supports a subclassification scheme based on the presence of nuclear atypia, similar to the approach recommended for the atypia of undetermined significance category

A Triumvirate:: Correlating Thyroid Cytopathology, Molecular Testing, and Histopathology

Risk stratification is essential in the preoperative evaluation and management of thyroid nodules, most of which are benign. Advances in DNA and RNA sequencing have shed light on the molecular drivers of thyroid cancer. Molecular testing of cytologically indeterminate nodules has helped refine risk stratification, triage patients for surgery, and determine the extent of surgery. Molecular platforms with high negative predictive values can help identify nodules that may be spared surgery and can be managed conservatively. Here we discuss the importance of integrating cytomorphologic, molecular, and histologic features to help avoid errors and improve patient management

Condyloma acuminatum of the urinary tract demonstrates atypical squamous cells in urine cytology

Urine cytology of urinary tract condylomas has not been systematically studied. We analyzed cytologic features of urinary tract condylomas and evaluated potential diagnostic challenges and pitfalls. We retrospectively reviewed urine cytology of urinary tract condylomas from 2 academic institutions (2015–2022). Among 20 patients with urinary tract condylomas, 6 had urine cytology (2 samples in 1 patient), including 3 men and 3 women (mean age, 74.3 years; range, 65–86 years). Original interpretations were negative for high-grade urothelial carcinoma (NHGUC; n = 4), atypical urothelial cells (n = 1), reactive urothelial cells (n = 1), and negative for malignancy (n = 1). Squamous cells were noted in 3 cases, atypical squamous cells (ASC) consistent with low-grade squamous intraepithelial lesion (LSIL) were noted in 1 case, and in 3 cases, the presence of squamous cells was not mentioned. All urines were reclassified according to The Paris System as NHGUC. Specimens were composed of benign urothelial cells and groups or isolated ASC consistent with LSIL (n = 4), atypical keratinized squamous cells (n = 2), and ASC that did not meet LSIL criteria (n = 1). The LSIL cells showed nuclear enlargement (n = 4), hyperchromasia (n = 4), perinuclear halo (n = 3), nuclear membrane irregularity (n = 4), orangeophilic cytoplasm (n = 3), and binucleation (n = 4). The atypical keratinized squamous cells showed hyperchromasia (n = 2), nuclear membrane irregularity (n = 2), keratin pearls (n = 2), and binucleation (n = 1). The ASC that did not meet LSIL criteria showed nuclear enlargement and orangeophilic cytoplasm. Many urinary tract condylomas (57%) demonstrate classic LSIL features in urine cytology. Less frequent cases can mimic keratinizing squamous cell carcinoma (28%) or demonstrate ASC not diagnostic of LSIL (15%). •Urinary tract condylomas are rare and can demonstrate cytologic features of low-grade squamous intraepithelial lesion.•Potential diagnostic pitfalls include a keratinizing squamous cell carcinoma.•The presence of atypical squamous cells in urine cytology should be documented

Benign and Malignant Granular Cell Tumor of the Hypopharynx: Two Faces of a Rare Entity

Granular cell tumors (GCT) are rare soft tissue tumors that involve the head and neck in 50% of patients. Two distinct variants of GCT, one benign (bGCT) and the other malignant (mGCT), involving the hypopharynx, a subsite of the larynx, are presented here. The clinical presentations, radiographic features, pathologic diagnosis in these two variants of GCT are discussed. The mGCT was diagnosed only after complete tumor excision. This report highlights the importance of complete excision of the tumor mass, as diagnosis of mGCT can be exceedingly difficult to make on a small biopsy specimen. Therefore, complete excision is recommended for definitive diagnosis and treatment of GCTs

TRPS1 immunohistochemical expression in salivary gland tumors: A pilot study

TRPS1 is a new, sensitive marker for breast carcinoma (BC). Salivary glands and breasts are both exocrine glands; thus, their tumors may share similar morphology and immunophenotype. Among salivary gland-type BC, TRPS1 is reported to be positive in secretory carcinomas (SCs) but negative in acinic cell carcinomas (AciCCs) and most adenoid cystic carcinomas (AdCCs). A subset of salivary duct carcinomas (SDCs) is positive for TRPS1. Herein, we investigate TRPS1 immunohistochemical expression in salivary gland tumors (SGTs). A retrospective search yielded 110 SGTs (97 primary and 13 metastatic). TRPS1 immunohistochemistry was scored as negative, low positive, intermediate positive, or strongly positive. TRPS1 was expressed in 78% (14/18) of pleomorphic adenoma (PA) cases but negative/low positive in all Warthin tumors (6/6 [100%]). In basal cell adenoma (BCA), TRPS1 expression was intermediate to strong (13/14 [92%]) in the stromal cells, whereas ductal or basal cells showed low expression. TRPS1 expression varied in malignant SGTs, with intermediate to strong staining in 100% (15/15) of AdCCs, 100% (5/5) of basal cell adenocarcinoma, 100% (3/3) of intraductal carcinoma, 89% (8/9) of polymorphous adenocarcinoma, and 89% (7/8) of SDCs; negative/low positive expression was observed in 100% (3/3) of SCs, 89% (8/9) of AciCCs, and 50% (3/3) of mucoepidermoid carcinomas. In addition, strong and intermediate TRPS1 expression was observed in metastatic SGT to the lungs, lymph nodes, and soft tissue. Overall, TRPS1 is strongly expressed in PA as well as malignant and metastatic SGT. In addition, TRPS1 is positive in stromal cells of BCA but negative or low positive in ductal and basal cells

Excision of rare adult cervical thymic cyst

Cervical thymic cysts (CTCs) represent 1% of all cervical cystic masses. A review of the literature found that CTCs are typically asymptomatic, with a propensity to be left sided. CTCs often require histological evaluation for diagnosis. A 27-year-old male patient presented to an outpatient otolaryngology clinic with worsening bilateral jaw and neck pain and an incidental right-sided neck mass found on cervical MRI. Preoperative differential diagnosis included venolymphatic malformation versus branchial cleft cyst. Histological examination of the excised specimen provided diagnosis of a CTC. Postoperatively, the patient reported improvement in cervical pain. CTCs are a rare cause of lateral neck mass in young adults. Typical presentation included neck enlargement with no symptoms or in some cases compressive symptoms. It is important to consider CTCs when formulating a differential for a lateral neck mass

Utility of high-risk HPV RNA chromogenic in situ hybridization in cytology smears and liquid-based preparations from metastatic head and neck squamous cell carcinoma

Background High-risk human papillomavirus (HR-HPV) status is critical for the diagnosis, prognosis, and treatment of patients with oropharyngeal squamous cell carcinoma (OPSCC). Patients often present with enlarged cervical nodes, and fine-needle aspiration cytology (FNAC) is frequently the initial diagnostic procedure. Although p16 is the most widely used surrogate marker, problems with interpretation can limit its utility in FNAC. HR-HPV RNA in situ hybridization (ISH) has emerged as a specific way to assess HPV status on cell block preparations of cervical nodes. The authors evaluated the utility of HR-HPV ISH in conventional smears and liquid-based cytology (LBC) preparations of metastatic head and neck squamous cell carcinoma (SCC). Methods Thirty-one aspirates of proven, HPV-related SCC (confirmed by p16 and/or HR-HPV ISH in corresponding surgical specimens) were selected. Ten aspirates of HPV-negative SCC were also retrieved. HR-HPV ISH was performed on 27 smears and 14 LBC preparations. All results were scored as positive, equivocal, or negative. Results Eighty-four percent of metastatic, HPV-related SCCs were positive for HR-HPV RNA ISH, with high number of signals (n = 19) and low number of signals (n = 7), whereas five HPV-related SCCs were equivocal. All metastatic, HPV-negative SCCs were negative for HR-HPV ISH. Conclusions HR-HPV ISH can be reliably performed on smears or LBC preparations, particularly when cell blocks are unavailable or paucicellular. Results were easy to interpret when high numbers of signals were present but were challenging in aspirates with low or rare number of signals. The current study suggests that HR-HPV ISH could be used as the initial testing modality for determining HPV status in FNAC specimens of metastatic SCC