Evaluation of the Aggressive-Variant Prostate Cancer Molecular Signature in Clinical Laboratory Improvement Amendments (CLIA) Environments.

Aggressive-variant prostate cancers (AVPCs) are a subset of metastatic castrate-resistant prostate cancers (mCRPCs) characterized by defects in ≥ two of three of TP53, RB1, and PTEN (AVPCm), a profile linked to lineage plasticity, androgen indifference, and platinum sensitivity. Men with mCRPC undergoing biopsies for progression were assessed for AVPCm using immunohistochemistry (IHC), next-generation sequencing (NGS) of solid tumor DNA (stDNA), and NGS of circulating tumor DNA (ctDNA) assays in CLIA-certified labs. Biopsy characteristics, turnaround times, inter-reader concordance, and inter-assay concordance were assessed. AVPCm was detected in 13 (27%) patients via IHC, two (6%) based on stDNA, and seven (39%) based on ctDNA. The concordance of the IHC reads between pathologists was variable. IHC had a higher detection rate of AVPCm+ tumors with the shortest turnaround times. stDNA had challenges with copy number loss detection, limiting its detection rate. ctDNA detected the greatest proportion of AVPCm+ tumors but had a low tumor content in two thirds of patients. These data show the operational characteristics of AVPCm detection using various assays, and inform trial design using AVPCm as a criterion for patient selection or stratification.

A pilot study: Comparison of TRPS1 and GATA3 immunoperoxidase staining using cytologic smears in entities reportedly positive for GATA3.

BACKGROUND: Metastatic breast carcinoma (mBC) is frequently encountered and may be challenging to diagnose as the tumor cells can morphologically resemble carcinomas of other primary origins. An additional challenge is that direct smears are often the only sample type available for immunostaining studies in cytology. Trichorhinophalangeal syndrome GATA-binding type 1 1 (TRPS1) is a highly sensitive marker for BC compared to the commonly used marker GATA3, especially in triple-negative BC (TNBC), in histologic samples. However, its sensitivity and specificity in mBC and other GATA3-positive tumors have not been studied. METHODS: The authors identified the following cytology cases: 37 GATA3-positive mBC cases and 19 available cases that were deemed mBC but were GATA3-negative during the original case workup and five cases of each of eight epithelioid entities known to have high rates of GATA3 positivity and commonly seen in cytology practice. Immunostainings of TRPS1 and GATA3 were performed on the chosen smears following standard protocols. RESULTS: TRPS1 was positive in all 37 GATA3-positive mBC cases and in 18 of the 19 GATA3-negative mBC cases. TRPS1 was negative in all five of the seven frequently GATA3-positive epithelioid entities, with the exception of salivary duct carcinomas where GATA3 was positive in a rate ranging 60%-100% among them. CONCLUSIONS: TRPS1 is as sensitive as GATA3 in GATA3-positive mBC and is more sensitive than GATA3 in TNBC. TRPS1 is negative in most GATA3-positive nonbreast tumors. Thus, the combination of TRPS1 and GATA3 could be used to differentiate breast primary from others in most situations.

Effect of the Paris system for reporting urinary cytology with histologic follow-up.

BACKGROUND: The Paris system (TPS) for Reporting Urinary Cytology provides a standardized reporting system whose main focus is the diagnosis of high-grade urothelial carcinoma (HGUC). We conducted a study to see the impact of The Paris System on our cytologic diagnoses with associated histology. MATERIALS AND METHODS: We reviewed our pathology database regarding urinary specimens in the year before implementation of The Paris System and the year after. We gathered the data regarding cytologic diagnosis and concurrent/subsequent histology. RESULTS: Over a 1-year period from 2016-2017, 486 urine cytology specimens were identified before implementation of The Paris System and diagnosed as follows: 83% benign/negative, 10% atypical, 2% suspicious, 5% HGUC, 0.2% low grade urothelial neoplasm (LGUN), and 0.2% unsatisfactory. Over a next 1-year period from 2017 to 2018, 602 specimens used TPS and diagnosed as follows: 85% negative for HGUC, 6% atypical, 3% suspicious, 4% HGUC, 0.17% LGUN, and 2% unsatisfactory. Although, not listed as a standardized category in The Paris System, our institution used "Negative for high-grade, cannot rule out low-grade urothelial neoplasm (NHL)" as a subcategory of Negative for HGUC. 4% of the cases fell into this category. Focusing on the Atypical category before TPS, histology was available in 15/49 (31%) cases. Of these, 40% had HGUC. Regarding the Atypical category after TPS, histology was available in 21/36 (58%) cases. Of these, 52% were HGUC. For the NHL category, concurrent histology was available in 13/26 (50%) cases. Of these, 67% were low grade urothelial neoplasms. CONCLUSION: Our study showed that TPS lowered the rate of Atypical from 10% to 6%. After the implementation of TPS, Atypical corresponded to a higher rate of high-grade urothelial carcinoma. Also, the NHL subcategory had a high positive predictive value for diagnosing low grade urothelial neoplasms.

Is Regional Lymph Node Metastasis of Head and Neck Paraganglioma a Sign of Aggressive Clinical Behavior: A Clinical/Pathologic Review.

BACKGROUND: Head and neck paraganglioma is a rare neoplasm of the paraganglia. It accounts for <1% of all head and neck tumors. It usually has benign clinical course; however, malignant paraganglioma can only be diagnosed by showing metastatic disease. We undertook a retrospective study to assess the clinical significance of regional lymph nodes metastases in head and neck paragangliomas. DESIGN: From 1993 to 2016, primary head and neck paragangliomas are identified. The patient clinical and histopathologic materials were reviewed. RESULTS: Sixty-five specimens from 62 patients (3 patients with more than 1 specimens) with head and neck paragangliomas were recorded (49 female and 13 males) with mean age of 54 (24-78 years). The locations of the tumors were as follows: carotid body: 30, glomus tympanicum: 11, glomus jugulare: 14, parapharyngeal space: 3, and 1 case each of larynx, skull base, paraglottic area, infratemporal fossa, mastoid, cerebellopontine (CP) angle, and pyriform sinus. On histopathology, we found 5 cases of sclerosing variant. Thirty-two (52%) of the 62 patients had regional lymph node biopsy. Four (12%) of the 32 show metastatic paraganglioma (3 females and 1 male with mean age = 35). Two of the 5 cases of sclerosing variant had positive lymph nodes. No evidence of local recurrence or distant metastasis in the patients with positive lymph nodes with a 6 to 11 years follow-up. One of the 28 patients with negative lymph nodes developed metastatic disease to lumbar spine in 5 years. CONCLUSION: Metastatic paraganglioma to regional lymph nodes may have indolent clinical behavior, with disease-free survival of up to 11 years. The incidence of metastatic disease in lymph nodes was 4 (12%) of 32. Forty percent (2/5) of the cases with sclerosing variant of paraganglioma had lymph node metastases indicating that this tumor may have a more aggressive histological behavior.

Metastatic head and neck cutaneous basal cell carcinomas: a retrospective observational study.

Cutaneous basal cell carcinoma is usually an indolent and slow-growing tumor with potential for local invasion and recurrence; however, metastatic events are exceedingly rare. The annual incidence of metastasis is estimated to range between 0.00281 and 0.05%. A retrospective search in the pathology database of a single tertiary institution was performed in the period between 1999 to 2019. Primary cutaneous metastatic basal cell carcinomas had paraffin blocks and glass slides retrieved. A total of 8673 cases was identified. The overall prevalence of metastatic tumors was 0.05% (4/8673). The median patient's age at diagnosis was 61 years old (range 52-79). The most common primary site of tumor was nose (2/4) and the most common histological subtype was infiltrative. The sampled lymph nodes were identified during primary tumor resection, except for 1 patient who had a sentinel lymph node biopsy performed as a surgeon individual decision. One patient had hematogenous spread to the pleura, diagnosed 5 years after diagnosis. In summary, this study adds new data to the current literature in metastatic primary cutaneous basal cell carcinomas and highlights the importance of early diagnosis and appropriate surgical excision in an effort to prevent local advanced disease, recurrence and lymphovascular dissemination.

Fine needle aspiration of an intrathyroidal parathyroid carcinoma mimicking a primary thyroid anaplastic carcinoma: A case report with review of the literature.

Intrathyroidal parathyroid carcinoma is an uncommon malignancy. A 46-year-old male presented with a left neck mass. Computed tomography (CT) scan revealed a hypodense mass in the left thyroid lobe along with evidence of metastatic lymphadenopathy. Aspiration of the left thyroid nodule was performed, and a diagnosis of malignancy was rendered, favoring a primary anaplastic carcinoma. Based on the cytologic diagnosis, the patient underwent a total thyroidectomy. Before the surgery, intact parathyroid hormone (PTH) and calcium level (PTH = 78 pg/mL; Calcium = 10.6 mg/dL) were found to be minimally elevated. On gross examination, a 3.2 cm mass within the left inferior thyroid lobe was seen. Histopathologic examination and ancillary studies supported the diagnosis of a parathyroid carcinoma. We, hereby present, an exceedingly rare presentation of an intrathyroidal parathyroid carcinoma with only minimal elevation of PTH and calcium, mimicking a primary anaplastic thyroid carcinoma on cytologic examination.

Acinic cell carcinoma of the salivary gland associated with lymphoid-rich stroma. A diagnostic dilemma on cytology: Study of two cases.

A lymphoid-rich stroma is a common finding in salivary gland tumors. Several reports documented this association with acinic cell carcinoma (ACC). However, cytologic studies reporting this phenomenon are rare and mainly confined to sporadic single case reports. We present the cytologic features of two cases of ACCs of the parotid gland displaying a lymphoid-rich background and discuss the cytologic differential diagnoses of this uncommon ACC variant.

Well-differentiated liposarcoma primary from thymic stroma: Case report and literature review.

Primary liposarcoma of thymic stroma is an exceptionally rare tumor. Histological findings are often definitive for diagnosis, however due to the variability of nuclear atypia and the overlapping with other adipocytic tumors, ancillary techniques are helpful as confirmatory tools. Currently, Fluorescent in situ hybridization for MDM2 is the gold standard for diagnosis of well-differentiated and dedifferentiated liposarcomas, however a panel of immunohistochemical stainings, including MDM2, CDK4 and p16 is available as alternative method, helping to distinguish liposarcoma from its benign counterpart lipoma, especially in borderline cases. We describe the case of a young female diagnosed with a well-differentiated lipomatous tumor primary of thymic stroma with near cut-off result for MDM2-FISHand positive immunohistochemical staining for the panel described above. We discuss the challenges in the diagnosis of this rare entity andpresent an updated literature review.

Non-human-papillomavirus-related malignancies of the vulva: A clinicopathological study.

BACKGROUND: Malignant tumor of the vulva is the fourth gynecological malignancy in frequency. Close to 70% of all vulvar malignancies are related to high-risk human papillomavirus (HPV) infection. METHODS: A search for non-HPV-related malignant tumors of the vulva was performed in the last 20 years (2000-2020) in the pathology database of a single tertiary institution. We aim to estimate the prevalence of non-HPV-related malignancies in our population, describe clinicopathological features of these tumors and investigate the expression of some potential therapeutic targets. RESULTS: A total of 71 patients were recovered; 26 patients (36%) had the diagnosis of extramammary Paget disease, 17 patients (24%) had basal cell carcinomas, 17 patients (24%) had primary melanomas, 10 patients (14%) had metastatic disease to the vulva and one patient (1%) had a primary dermatofibrosarcoma protuberans. Fifty-four percent of patients with extramammary Paget disease had a secondary malignancy and 12.5% had invasive disease. Programmed death-ligand 1 (PDL-1) was positive in seven out of nine primary melanomas and Her2/neu was overexpressed in six out of seven extramammary Paget disease. CONCLUSION: Non-HPV-related malignancies are important differential diagnoses in patient with vulvar lesions. Additional research is necessary to further understand these complex malignancies and potential new therapeutic targets.

Mycobacterium Spindle Cell Pseudotumor Caused by Mycobacterium xenopi: A First Described Association of a Rare Entity Presenting in the Lung.

Mycobacterial spindle cell pseudotumor (MSP) is a rare benign lesion characterized by a proliferation of bland spindle-shaped histiocytes with vague granulomatous formation, positive for acid-fast bacilli staining. This lesion is usually reported in the lymph nodes and skin of immunocompromised patients; only 6 cases primary in the lung have been reported in the English literature to this date. In this article, we present the case of a 42-year-old female status post failed kidney-pancreas transplant with subsequent multiple kidney transplants, on chronic immunosuppression, who developed a mass in the left lower lobe consistent with MSP. Mycobacterium xenopi was identified in lung tissue culture, an association never previously described in literature. This case report alerts for the possible association of this rare form of non-tuberculous mycobacteria in the pathogenesis of MSP and highlights the importance of this differential diagnosis in lung masses of immunocompromised patients.

Follicular cystitis in urine cytology: A clinical and cytopathologic study.

Despite being an important differential diagnosis of bladder tumor on cystoscopy, follicular cystitis (FC) is rarely diagnosed on cytologic material. We performed a retrospective study on cases of FC diagnosed on bladder biopsy and/or urine cytology in our institution. A total of 35 cases of FC were identified with a female predominance (F:M = 2:1). Hematuria was the most common clinical presentation. Cystoscopic findings included mass lesions, yellow plaques, and surface erythema. History of urinary tract infection was reported in 48% of the patients, and majority of those patients had positive concurrent urine culture, most commonly with beta-hemolytic streptococcus, Group B. A total of 17 out of 35 patients had urine cytology specimens. When the presence of follicular dendritic cells in clusters of variously sized lymphocytes is used as the cytological diagnostic criterion, 6 out of 17 cases were diagnosed as FC and 5 out of 6 were confirmed by concurrent biopsy. This retrospective study not only analyzed the clinical characteristics of FC but also elucidated the cytological diagnostic criteria of FC and confirmed its specificity.

Metastatic granular cell tumor to the breast diagnosed by fine needle aspiration cytology: A case report with review of the literature.

Granular cell tumors (GCT) are mesenchymal neoplasms of Schwann cell/neural origin. Malignant granular cell tumors (MGCTs) represent <1-2% of all GCT and defined as tumors demonstrating metastases or destructive local growth. Other clinical parameters suggestive of malignancy include rapid growth, size > 4 cm and necrosis. An apparently inconsistent set of histological features have been described in MGCT. Although the histologic parameters of a GCT are not always predictive of biologic behavior, the presence of atypical features may be indicative of an aggressive clinical behavior (recurrence and metastases). A preoperative estimate of features suggestive of malignancy is important for treatment and prognostication. Diagnosis and prognostication from preoperative fine needle aspiration (FNA) cytology is hampered by the fact that only a few case reports on cytologic features of malignant GCT have been published. We report a case of metastatic MGCT to breast and compare cytologic features to that of primary breast GCT and apocrine/histiocytoid variants of breast carcinoma.

Role of fine-needle aspiration in post liver transplant patients: A clinical/cytological review.

BACKGROUND: Fine-needle aspiration (FNA) of superficial and deep-seated lesions has been used with high sensitivity and specificity in the diagnosis of neoplastic and nonneoplastic lesions. However, literature of FNA in posttransplant patients is sparse, especially in postliver transplant. We undertook a retrospective study to evaluate the utility of FNA in the clinical management of post liver transplant patients. METHODS: We searched our institution's surgical/cytologic databases (November1993-February2016) to identify liver transplant cases and FNA procedures performed on allograft liver recipients. Institutional IRB approval was obtained for this study. RESULTS: 886 liver allograft recipients were reviewed, 41(5%) of which were transplanted for hepatocellular carcinoma. 62/886(7%) underwent an FNA procedure. 39males and 23females included with mean age of 58years. Mean time between transplant and FNA was 34months. 21/62(34%) were malignant neoplasms, most common malignancy was adenocarcinoma: 8cases(3lung,3pancreas,1colon,1cholangiocarcinoma)and 8cases of transplanted hepatocellular carcinoma patients had recurrence, 6 in the allograft liver and 1case each of metastasis to the iliac bone and periportal lymph node. 3cases were squamous-cell carcinoma (2lung and 1scalp). 2cases were posttransplant lymphoproliferative disorders. 34/62(55%) cases were benign aspirates from various organs (8lung,6liver,5pancreas,4breast,3thyroid,3lymph-nodes and 1case each of salivary gland, bile-duct,intraabdominal,abdominal wall,and oral cavity) 0.6/62(10%) cases were inflammatory. 22cases had histologic correlation: 5true-positives,16true-negatives,1false-negative (a patient with parotid mucoepidermoid carcinoma whose FNA diagnosis was sialadenitis), and no false-positive. The sensitivity was 83% and the specificity was 100%. The positive predictive value was 100% and the negative predictive value was 94%. CONCLUSIONS: This review shows that 40/62(65%) of the aspirates were benign lesions, indicating that a conservative approach is recommended in the clinical management of these patients, especially since the interval between transplant and FNA was on average 34months. FNA is a safe, minimally invasive method to follow-up these patients.