Utility of parathyroid hormone immunocytochemistry in fine needle aspiration diagnosis of parathyroid tissue.

OBJECTIVE: The cytomorphological features of parathyroid tissue (PTT) may overlap with those of thyroid lesions, thus posing a diagnostic challenge. In this retrospective study, we reviewed our institutional experience in using parathyroid hormone (PTH) immunocytochemistry (ICC) to substantiate the diagnosis of PTT on fine needle aspiration (FNA). METHODS: Our pathology database was searched for FNA cases in which PTH ICC was performed between 1 January 2015 and 31 March 2022. PTH ICC was performed on a ThinPrep slide in cases with a clinical suspicion of PTT or with cytomorphological features raising the possibility of PTT. Patients' clinicopathological characteristics, PTH ICC results, cytological diagnoses, and surgical follow-ups, if available, were reviewed and analysed. RESULTS: The study cohort included 103 cases clinically designated as thyroid (n = 85, 82.5%), parathyroid (n = 11, 10.7%) and neck soft tissue (n = 7, 6.8%). PTH immunostaining was negative, positive, and indeterminate in 53 (51.5%), 27 (26.2%), and 23 (22.3%) cases, respectively. Surgical follow-up was available in 27 (26.2%) cases, including 17 thyroid lesions and 10 PTT cases. All positive PTH cases were confirmed to be PTT, while all but one of the negative PTH cases were non-PTT on follow-up. The calculated sensitivity, specificity, positive and negative predictive values were 85.7%, 100%, 100% and 93.3%, respectively. CONCLUSION: Our study demonstrates that PTH ICC performed on additional ThinPrep slides is a valuable adjunct test in FNA samples with a differential diagnosis of PTT vs non-PTT. Low cellularity may be a limiting factor in the accurate assessment of PTH by ICC.

SS18-SSX Expression in a Contemporary Cohort of Primary Renal Synovial Sarcoma: A Multi-Institutional Experience of Fourteen Patients.

Primary renal synovial sarcoma is a rare aggressive mesenchymal neoplasm of the kidney that accounts for less than 1% of renal sarcomas. Herein, we describe the clinicopathologic and molecular findings of 14 renal synovial sarcoma patients in one of the largest case series to date and to our knowledge, the only renal synovial sarcoma series to use novel SS18-SSX IHC. Clinicopathologic, IHC, molecular, management, and follow-up data were reviewed and analyzed. Macroscopically, the tumors had either homogeneous, tan-white, and solid (n = 10), variegated and solid (n = 3), or variegated and solid-cystic (n = 1) cut surfaces. Spindle cell (n = 10), round cell (n = 3), and round to epithelioid morphologies (n = 1) were observed. SS18-SSX IHC was positive in all 14 tumors (diffuse, n = 10; multifocal, n = 2; focal, n = 2). All the tumors harbored SS18::SSX1/2 gene rearrangement. Metastases to the liver, brain, and lung (n = 1); liver and bone (n = 1); liver and diaphragm (n = 1) were identified. Adjuvant chemotherapy was administered in 11/12 patients. Follow-up was available for 10 patients (time period range: 5 to 24 months). Four patients died of disease, and six patients are alive with no recurrence or metastasis. As SS18-SSX IHC showed an excellent concordance with the FISH results, this may reliably be used in the IHC panel of spindle/round cell sarcomas of the kidney and as a molecular surrogate for renal synovial sarcoma, particularly in a resource-limited setting. Also, the tumors with focal SS18-SSX expression had lower break apart signals in the FISH assay (19% and 23% in two tumors with focal SS18-SSX IHC positivity).

Accuracy of whole slide image based image analysis is adversely affected by preanalytical factors such as stained tissue slide and paraffin block age.

Background: Personalized medicine and accurate quantification of tumor and biomarker expression have become the cornerstone of cancer diagnostics. This requires Quality Control (QC) of research tissue samples to confirm adequate targeted tumor tissue sampling. Digitalization of stained tissue slides offer a precious way to archive, preserve, and retrieve necessary information when needed. This study is aimed to assess the most significant pre-analytic and analytic factors that might contribute to the efficacy of obtaining accurate whole slide images (WSIs) interpretation. Various studies are needed to identifysuch factors to allow for appropriate AI application and adequate tumor area/percentage quantification. Methods: Hematoxylene and Eosine (H&E) satined WSIs collected from tissue specimens provided by the Cooperative Human Tissue Network (CHTN) Midwestern Division (CHTNMWD) were analyzed. Tissue specimens were processed, fixed, stained, and scanned contemporaneously (within 1 month). Two cohorts of malignant, colorectal cancer, 20X WSI (ScanscopeXT, Leica Biosystems, Illinois), were assembled. The study identified a "recent cohort" that included 76 WSIs created on 2018 or later. "Aged cohort" included 73 WSIs from specimens procured in the period of (2012-2014). Twenty recent WSIs of adenocarcinoma cases were used to construct WSIs analysis algorithms (VIS, Visiopharm A/S, Denmark) using machine learning to produce morphometric maps and calculate tissue and tumor areas. Results: Algorithmic analysis of 69 WSIs from rescanned aged slides vs. that of contemporaneous WSIs concluded 18 (28%) similar finding in tumor areas (within 10%), 56 (82%) had identicaltissue areas, and 54 (79%) had similar tumor percentages. Conclusion: WSIs of aged H&E slides and stained paraffin block re-cuts produce different tumor quantification compared to those of original scanned sslides most likely due to pre-analytical factors. The difference in tumor area detected between original and rescanned WSIs trended upward in the period between 2012 and 2014. Less tumor area was detected as the slides age. Recut and H&E-stained tissues from stored paraffin blocks may detect more tumor due to excess eosinophilia. These results highlights the value of documenting archives of H&E WSIs collected at the procurement time. Such images provide a superior archive over glass slides and Formalin-Fixed Paraffin-Embedded (FFPE) blocks and contribute betterg to WSIs analysis application.

Does Immunohistochemistry Add to Morphology in Differentiating Trichoepithelioma, Desmoplastic Trichoepithelioma, Morpheaform Basal Cell Carcinoma, and Microcystic Adnexal Carcinoma?

BACKGROUND: The distinction among cutaneous basaloid neoplasms such as trichoepithelioma (TE), desmoplastic trichoepithelioma (DTE), morpheaform basal cell carcinoma (MBCC), and microcystic adnexal carcinoma (MAC) can be difficult, especially in superficial biopsies. As the treatment plan of each entity is different, accurate characterization is important for appropriate management. While TE and DTE are benign neoplasms with indolent behavior, MBCC and MAC are typically locally aggressive. The expression of several recently described immunohistochemical (IHC) markers, including p40, IMP3, and ProEx C, has not been adequately established in cutaneous neoplasms. We explored the potential utility of a broad IHC panel, including previously reported and novel markers to differentiate TE, DTE, MBCC, and MAC. DESIGN: A total of 35 archival cases [TE (n=14), DTE (n=9), MBCC (n=6), and MAC (n=6)] were stained with 9 IHC markers: p40, IMP3, ProEx C, p16, CK20, Ki-67, androgen receptor, D2-40, and beta-catenin. Tumors with >5% immunoreactivity were scored as positive. The intensity was scored on a scale from 1+ to 3+. The pattern of positivity- nuclear, cytoplasmic, membranous, or in combination; peripheral or central distribution with lesion was also recorded. RESULTS: CK20 (in contrast to prior studies) and IMP3 were negative in all cases. Likewise, with the exception of one case of TE, androgen receptor showed no immunoreactivity in all categories. No significant difference was observed in the expression of beta-catenin, p16, ProEx C, and p40 among the four groups of cutaneous neoplasms. The mean Ki-67 labeling index for MBCC (8%) was slightly higher than DTE (3%). Interestingly, the proliferation index for TE (15%) was significantly higher than that of MBCC. All six cases of MAC and 36% of TEs expressed D2-40; neither the MBCC nor DE cases showed D2-40immunoreactivity. Also, we confirmed the previously published observation of scattered CK20 positive Merkel cells in the epidermis of all cases of DTE; whereas, no Merkel cells were identified in MBCC and MAC cases. CONCLUSIONS: Except Ki-67, our IHC panel showed no significant added diagnostic utility of IHC in discriminating among TE, DTE, MBCC, and MAC. Among the four cutaneous neoplasms, DTE and MBCC show a small but discernible difference in Ki-67.

p53 and p16ink4a As Predictive and Prognostic Biomarkers for Nodal metastasis and Survival in A Contemporary Cohort of Penile Squamous Cell Carcinoma.

BACKGROUND: Human papilloma virus (HPV) infection is implicated in a proportion of invasive squamous cell carcinoma of the penis (PC). A subset of PC involves dysregulation of the p53 pathway. HPV in situ hybridization (ISH) and p16ink4a positivity are surrogate markers for HPV infection, and p53 immunohistochemistry (IHC) denotes abnormality in the p53 pathway. There remains an ambiguity with regard to the contribution of both the pathways in the prognosis of PC. We sought to analyze the clinicopathologic characteristics of a cohort of Indian PC patients with respect to p16 ink4a and p53 expression. PATIENTS AND METHODS: A cohort of 123 PC patients was studied for p16ink4aand p53IHC and HPVISH. The results of these biomarkers were correlated with various clinicopathologic parameters. RESULTS: p16ink4a and HPV ISH were positive in 47% and 53% of the tumors, respectively. The proportion of warty, basaloid, or mixed warty-basaloid tumor subtypes showed significant p16ink4apositivity (P < .0001) compared to other subtypes. Twenty-eight patients were dual negative (p53- /p16ink4a-), 32 were dual positive (p53+/p16ink4a+), 38 were p53+/p16ink4a-, and 25 were p53-/p16ink4a +. In patients where p16ink4a was negative, a p53-positive phenotype had a higher propensity for lymph node metastases (OR, 5.42; 95% CI, 1.75-16.80; P = .003). Similarly, p53 positivity dictates nodal involvement in the p16ink4a-positive subset of tumors (OR, 5.00; 95% CI, 1.23-20.17; P = .024). On multivariate analyses, pathologic subtypes (warty, warty-basaloid, and basaloid) (P < .0001), p16ink4aexpression (P < .0001), and absence of nodal metastasis (P < .0001) were significant predictors of improved overall (OS) and cancer specific survival (CSS). In Kaplan-Meier analysis, the OS was significantly longer in patients with p16ink4a + tumors (P < .0001), as was the CSS (P < .0001). Patients with dual positive tumors had a significantly higher OS (P < .001) and CSS (P = .012), in the entire cohort. In the node positive patients, dual positivity was associated with significantly higher OS (P < .0001); however, the median CSS for p53+/p16ink4a+tumors were not significantly different compared to p53- /p16ink4a- tumors (P = .064), although there was a trend towards improved CSS. CONCLUSIONS: There is a strong concordance between p16ink4aIHC and HPV ISH results. p16ink4a status is an independent predictor of survival (OS and CSS) in our cohort of PCs. p53 is a predictor of nodal metastasis irrespective of p16 status. Dual positive tumors have a significantly better outcome in comparison to dual negative tumors.

Light chain deposition disease presenting as an atrial mass: a case report and review of literature.

Light chain deposition disease (LCDD) also known as nonamyloidotic immunoglobulin deposition disease is a rare systemic disorder due to the abnormal deposition of immunoglobulin in multiple organs caused by the clonal proliferation of B lymphocytes and plasma cells. Renal involvement is the most common with cardiac manifestations being the most common extra renal presentation of the disease. Renal involvement is not always associated with LCDD. Isolated cardiac involvement can manifest in a wide variety of ways: heart failure, cardiomyopathy, arrhythmias, angina, myocardial infarction, etc. We hereby present an unusual case of 59-year-old female who presented to clinic for routine follow up. A murmur on physical exam was evaluated with echocardiogram which led to the discovery of an incidental right atrial mass. Cardiac magnetic resonance imaging was completed 6 months later for follow up which showed increasing size of the mass. The mass was excised and found to be consistent with LCDD. To the best of our knowledge, this is the first reported case of LCDD manifesting as an atrial mass. Through this case report and review of literature we would like to generate awareness among our fellow pathologists and clinicians to maintain a high level of suspicion for LCDD as it can manifest in many unusual ways, with or without kidney involvement.

Epithelium Involving Bilateral Axillary Lymph Nodes: Metastasis, Misplaced, or Mullerian!

During breast cancer staging, histological evaluation of axillary sentinel lymph nodes (SLN) is usually straightforward. However, the exact characterization of a small epithelial deposit in an SLN can be challenging, especially during the frozen section examination. We report the first case of endosalpingiosis involving bilateral axillary lymph nodes. We review published literature on axillary endosalpingiosis and discuss the differential diagnosis of small epithelial deposits in an axillary SLN. Pathologists should consider benign epithelial rests and displaced epithelium as differential diagnoses for the microscopic epithelial nodal deposit, especially during the frozen section examination.

Unusual cerebrospinal fluid finding of intracytoplasmic granules in metaplastic carcinoma of the breast with acinar differentiation.

Cerebrospinal fluid (CSF) evaluation for total and differential cell count is a common practice in pathology for evaluation of various disease conditions. Although rare, these CSF samples yield interesting and unusual morphological findings, which are not only of academic interest, but also may play key roles in diagnosis. For diagnosing metastatic carcinoma in brain and meninges, CSF examination is one of the important tools along with imaging studies. Metaplastic breast carcinoma (MBC) encompasses a rare (<1% of all breast cancers), aggressive and highly heterogeneous group of tumors. MBC is almost always estrogen receptor, progesterone receptor and Her2 negative (triple negative) and shows frequent early distant metastases as well as sub-optimal response to systemic therapies. The involvement of leptomeninges is most commonly associated with these triple- negative subtypes. In this report, we present an unusual case of malignant cells with prominent intracytoplasmic granules in CSF smears of a 46-year-old female with metastatic MBC with acinar differentiation. An extensive review of literature in English language did not return any other reports of a similar finding.