Navigating the diagnostic maze: the challenge of sclerosing pneumocytoma in frozen sections.

Pulmonary Sclerosing Pneumocytoma (PSP) represents a rare benign tumor that exhibits a predisposition towards females. Often asymptomatic, its identification usually occurs incidentally through imaging modalities. Histologically, PSP demonstrates features consistent with pneumocytic differentiation and possesses a dual-cell population. However, in rare instances it may demonstrate pleural invasion or lymph node metastasis. Diagnosing PSP through small biopsy or frozen section presents considerable challenges attributed to its heterogeneous growth patterns and striking similarity to well-differentiated pulmonary adenocarcinoma. We report a case of PSP in a 57-year-old female smoker, presenting as a slow-growing 2.5 cm mass that recently exhibited enlargement, as noted on computed tomography (CT) scan. The recommendation for excising the mass prompted the patient to undergo a right robotic-assisted thoracoscopic procedure, which entailed wedge resection of the right lower lobe and an intraoperative consultation. A completion right lower lobectomy was performed, accompanied by lymph node dissection, following a frozen section diagnosis indicating at least adenocarcinoma in situ. The permanent section revealed bland cuboidal cells lining papillary and sclerotic areas, with occasional atypical features such as prominent nucleoli and scattered mitotic figures. Adjacent foci of atypical adenomatous hyperplasia (AAH) were noted. Immunohistochemical (IHC) staining revealed positive Napsin A, keratin AE1/3, and CK7 in surface cells but not in round cells. Both EMA and TTF1 immunostains highlighted surface cells and scattered round cells. Elastic stain highlighted visceral pleural involvement. The combined morphology and immunoprofile supported the diagnosis of PSP. This case underscores the critical importance of accurately diagnosing slow-growing pulmonary nodules, which are increasingly detected by the widespread use of imaging for various medical conditions.

Hyalinising clear cell carcinoma with a novel fusion gene: Insights into the diagnosis.

Hyalinising clear cell carcinoma (HCCC) is a rare salivary gland neoplasm characterised by an EWSR1::ATF1 fusion. Rare cases showing EWSR1::CREB1 rearrangements have been reported. This article presents a case of HCCC with a novel EWSR1-CREB1 fusion, diffuse eosinophilic appearance, novel cytomorphological findings, PAS-negativity, and late regional and distant lymph node metastases.

Microwave Ablation for Malignant Central Airway Obstruction: A Pilot Study.

BACKGROUND: Malignant central airway obstruction (CAO) is a debilitating complication of primary lung cancer and pulmonary metastases. Therapeutic bronchoscopy is used to palliate symptoms and/or bridge to further therapy. Microwave ablation (MWA) heats tissue by creating an electromagnetic field around an ablation device. We present a pilot study utilizing endobronchial MWA via flexible bronchoscopy as a novel modality for the management of malignant CAO. METHODS: Therapeutic bronchoscopy with a flexible MWA probe was performed in 8 cases. We reviewed tumor size, previous ablative techniques, number of applications, ablation time, amount of energy delivered, rate of successful recanalization, complications, and 30-day follow-up. RESULTS: Successful airway recanalization was achieved in all cases. No complications were noted. In 1 case, tumor in-growth within a silicone stent was ablated with no damage to the stent. DISCUSSION: Endobronchial MWA is a novel technique for tumor destruction while maintaining an airway axis. The oven effect and air gap around a tumor allow for safe and effective tissue devitalization and hemostasis without a thermal effect on structures surrounding the airway.

An Anatomic Curiosity: A Sliver of a Liver in an Unusual Location.

A 48-year-old woman underwent preoperative cardiac testing prior to gastric bypass. She was incidentally found to have a right atrial mass on transthoracic echocardiography. Subsequent cardiac magnetic resonance confirmed this finding. She underwent excision of the mass. Tissue pathology revealed ectopic hepatic tissue. (Level of Difficulty: Advanced.).

DFSP of the Breast: Histomorphological, Immunohistochemical, and Molecular Features of a Rare Case in an Unusual Location.

We present a case of a 21-year-old female with a vague nontender mass in the lower inner quadrant of the left breast discovered incidentally on chest imaging following trauma. A breast ultrasound demonstrated an 8×6×8 mm irregular hyperechoic mass at the 7 o'clock position of the left breast, 9 cm from the nipple. The mass was graded Breast Imaging Reporting and Data System (BI-RADS) category 4 (suspicious finding). An ultrasound-guided biopsy of the mass showed a proliferation of monotonous spindled cells in a storiform pattern with tapered nuclei with infiltration into the adipose tissue. No normal breast elements were identified in the biopsy. Myofibroblastoma was the first differential diagnosis; however, the characteristic infiltrative pattern of the tumor mandated additional tests including fluorescence in situ hybridization to rule out a dermatofibrosarcoma protruberance (DFSP). Immunohistochemical staining showed positive staining for CD34, which can be positive in myofibroblastoma also. However, fluorescence in situ hybridization demonstrated a platelet-derived growth factor B (22q13.1) gene rearrangement confirming a diagnosis of DFSP. The patient underwent a wide local excision of the DFSP for definitive treatment. She is doing well with no recurrence reported so far, after 15 months of follow-up. Conventional DFSP does not metastasize but is prone to recurrence making wide margins imperative for definitive treatment.

To whom the specimen goes: a look at how touch preparations and core needle biopsies are handled in different practices and the effect on fellowship education.

INTRODUCTION: Core needle biopsies (CNBs) have proven to be an excellent source of tissue for diagnosis and ancillary testing in the era of personalized medicine, commonly yielding sufficient material for testing via a relatively minimally invasive technique. Thus, there has been an increase in touch preparations (TPs) evaluated with rapid onsite evaluation (ROSE) of these small biopsies either in isolation or with concurrent fine needle aspiration (FNA). This in turn has forced cytopathology practices to make decisions with regard to processing and workflow of CNBs, which affects cytopathology fellowship education substantially. STUDY DESIGN: The present review is based on a review of recent literature and an evaluation of the authors' personal experiences. RESULTS AND CONCLUSIONS: Deciding whether CNBs with associated TPs should be assigned to the cytology service, the subspecialty or general surgical pathology service, or a split between cytopathology and surgical pathology, is complicated. The workflow is variable at different institutions depending on multiple factors. Each of these routes has benefits and disadvantages that can affect patient care and laboratory workflow, in addition to having downstream effects on the quality and type of education our pathology trainees receive. Herein, the advantages and disadvantages of the different approaches for CNB triage are discussed, with an emphasis on the impact upon cytopathology fellowship education.

Analysis of the risk of malignancy associated with the basaloid and oncocytic subtypes of the salivary gland neoplasm of unknown malignant potential (SUMP) category in the Milan system.

BACKGROUND: The salivary gland neoplasm of unknown malignant potential (SUMP) category reflects the cytomorphologic overlap and complexity of reporting salivary gland cytology in the Milan system. It includes neoplasms for which a diagnosis of a specific entity cannot be made and, more importantly, for which a carcinoma cannot be entirely excluded. For risk stratification, the subcategorization of SUMP based on the predominant cell type is recommended. This study was aimed at evaluating the risk of neoplasm (RON) and the risk of malignancy (ROM) of the basaloid and oncocytic subtypes of the SUMP category. METHODS: A retrospective analysis of 482 salivary gland fine-needle aspirations from 2012 to 2019 resulted in 48 SUMP cases. The cytology of these cases was reviewed and reclassified as the basaloid or oncocytic subtype. Surgical follow-up was available for 36 cases. The RON and ROM for each subtype were calculated. RESULTS: The RON and ROM were 100% and 23%, respectively, for monomorphic basaloid tumors and 88% and 58.8%, respectively, for monomorphic oncocytic tumors. The ROM for basaloid tumors was 8.3% without matrix/with minimal matrix and 60% with an nonfibrillary matrix. The ROM for oncocytic tumors was 50% without a cystic background and 60% with a cystic or mucinous background. The difference was not statistically significant for either of the subgroups. CONCLUSIONS: Even though statistically not significant in our study, the differential ROMs within the oncocytic and basaloid subgroups help in the risk stratification of SUMP cases. Further subcategorization based on the stroma and background helps in limiting the differential diagnosis but does not necessarily add to the value of the risk stratification.

Impact of the Milan System for Reporting Salivary Gland Cytology on risk assessment when used in routine practice in a real-time setting.

INTRODUCTION: Several retrospective studies across the world have validated the role of the Milan System for Reporting Salivary Gland Cytology (MSRSGC) in improving communication between pathologists and clinicians. In this study, we evaluated the applications of MSRSGC in a real-time setting for 2 years. MATERIALS AND METHODS: All salivary gland lesions that underwent fine-needle aspiration (FNA) from January 2018 to December 2020 were categorized according to MSRSGC guidelines. The risk of malignancy (ROM) was calculated for each category and compared with the ROM proposed by MSRSGC and recent retrospective studies. RESULTS: A total of 160 FNA of salivary gland lesions were categorized as: nondiagnostic (ND) 30 (18%), non-neoplastic (NN) 7 (10.6%), atypia of undetermined significance (AUS) 5 (3.1%), benign neoplasm (BN) 59 (36.8%), salivary gland of uncertain malignant potential (SUMP) 21 (13%), suspicious for malignancy (SM) 3 (1.84%), and malignant (M) 25 (15.6%). Histopathologic follow-up was available for 94 (57.5%) cases. The ROM for each category was ND 54%, NN 0%, AUS 66%, BN 0%, SUMP 37.56%, SM 100%, and M 100%. CONCLUSION: With strict adherence to the diagnostic criteria and MSRSGC guidelines, a ROM of 100% in SM and M categories and a ROM of 0% in NN can be achieved in a real-time setting. The high ROM in the ND category in our study highlights the value of repeat FNA/biopsy for this category. High ROM for AUS indicates the tendency to classify high-grade tumors as AUS, calling for refinement in its criteria.

Threshold for interpretation of p16 immunostaining in fine-needle aspirate specimens of metastatic oropharyngeal squamous cell carcinoma.

INTRODUCTION: Human papilloma virus (HPV)-associated oropharyngeal squamous cell carcinoma (HPV-OPSCC) has been recognized to have an excellent response to treatment and has a distinct pathologic staging. For this reason, HPV testing is recommended in cytology specimens of metastatic OPSCC, although the guidelines for testing are not clearly defined. The aim of the current study was to establish a threshold for interpretation of p16 in aspirates from metastatic OPSCC. MATERIALS AND METHODS: Cases diagnosed as metastatic SCC by cytology in neck lymph nodes with concurrent p16 on cytology and on paired surgical specimen or an in situ hybridization (ISH) for HPV were included in the study. Stain intensity and percentage positive cells for p16 was compared with p16 on paired surgical pathology specimens and/or ISH RNA for HPV on cytology specimens. RESULTS: Of the 52 cases diagnosed as metastatic SCC on neck aspirates, paired surgical pathology specimens and/or ISH HPV was available in 17 cases. A p16 expression in ≥10%-15% cells resulted in a sensitivity and negative predictive value of 66% and 37%, respectively. However, when even minimal expression in tumor fragments is considered positive, the negative predictive value increases to 100%. CONCLUSIONS: We recommend that even minimal nuclear expression for p16 in viable tumor fragments must be considered as positive in cytology specimens. Expression limited to only background single tumor cells or in a necrotic specimen must be interpreted with caution.

Large Tumefactive IgG4-related Disease: Histologic, Cytologic, and Immunohistochemical Features of a Very Unusual Case.

Immunoglobulin G4-related disease (IgG4-RD) is a regional or systemic multiorgan lymphoplasmacytic inflammatory disease of unknown etiology. It has been described in numerous organs and anatomic locations. Review of the literature shows that when the disease involves the retroperitoneum it causes retroperitoneal fibrosis. Tumefactive IgG4-RD of the retroperitoneum has not been previously reported. In this report, we describe the first case of a large retroperitoneal tumefactive IgG4-RD along with its histologic, cytologic, and immunohistochemical characteristics.

Rapid On-site Evaluation of Spine Lesions.

Fine-needle aspiration (FNA) and core needle biopsy are the primary diagnostic modalities for assessing mass lesions. Any superficial or deep-seated lesion occurring anywhere in the body, including bone and soft tissue, can undergo this procedure to pathologically characterize it. The outcomes of FNA, performed either alone or in combination with core biopsy, are best when performed and interpreted by skilled individuals. The roles of interventional radiologists and cytologists are pivotal in ensuring adequacy of the specimen and leading the clinical team in making the diagnosis and avoiding repeat diagnostic procedures or a more invasive open surgical biopsy.

Role of cytology and immunochemistry in diagnosis of metastatic malignancies in the lung: A critical appraisal.

BACKGROUND: Lung is one of the most common sites for primary and metastatic malignancies and a challenging site to diagnose primary versus a metastatic origin of the tumor on cytology. Pathologic diagnosis of the site of origin of cancer has major implications in the management and staging purposes and may have to be followed by testing for predictive/prognostic markers. The clinical history of a known extrapulmonary primary and the radiologic findings of multiple nodules in the lung are useful in arriving at the right diagnosis but is not always available. Rarely pulmonary metastasis may be the first manifestation of an extrapulmonary tumor or may even present as a single nodule. METHOD: In this study, we reviewed cytomorphologic features of tumors metastatic to the lung (2014-2017) in conjunction with immunochemistry and evaluation of needle core biopsy when available. The review of the slides was performed with an emphasis on our ability to identify the site of origin in the tumors. RESULTS: We identified 47 cases of metastatic tumors in the lung diagnosed on cytology. Clinical history was available in 83% cases and with aid of immunostains, a definitive diagnosis on the origin of the tumor was made in all these cases. In the remaining 8 cases, a primary origin could only be suggested. The use of immunochemistry facilitated the diagnosis but could be misleading. CONCLUSION: The approach to the diagnosis of metastatic tumors in the lung on cytology should be largely guided by the previous clinical history and comparison with previous tissue/cellular material if available.

Osteitis fibrosa cystica masquerading as bone neoplasm.

A 50-year-old female patient with no significant medical history presented with left knee pain. Radiographs of the knee showed a circumferential swelling of the distal femur suggestive of neoplasia. Further evaluation revealed multiple lesions in the left iliac bone and proximal femur. Biopsy was suggestive of a reparative granuloma or an aneurysmal bone cyst. Laboratory assessment showed hypercalcaemia and elevated parathyroid hormone consistent with severe primary hyperparathyroidism. Osseous survey was significant for salt and pepper appearance of the skull. Ultrasound of the neck and 99mTc-sestamibi parathyroid scintigraphy localised a left parathyroid adenoma/carcinoma. Parathyroidectomy was successful, and a large parathyroid adenoma was excised. Six months later, the patient was doing fine with her gait returning to normal. On follow-up 2 years later, she had no recurrence of the lesions.

Cyto-histological correlation of Xp11.2 translocation/TFE3 gene fusion associated renal cell carcinoma: Report of a case with review of literature.

The MiT family translocation renal cell carcinomas (RCCs) are relatively rare in comparison to the conventional RCC. The cytologic features overlap with conventional clear cell RCC and papillary RCCs, thereby making the diagnosis extremely challenging. Here, we describe a case of TFE3 translocation associated RCC in a 58-year-old patient, with emphasis on cytomorphologic features and clues toward this diagnostic entity. Correlating the cytohistologic findings and review of touch imprints revealed that presence of hyaline nodules resembling leisegang rings and psammoma bodies in cytologic smears from kidney tumors serve as an important clue in raising a suspicion for the diagnosis of MiT family translocation RCCs.

Targeting MTA1/HIF-1α signaling by pterostilbene in combination with histone deacetylase inhibitor attenuates prostate cancer progression.

The metastasis-associated protein 1(MTA1)/histone deacetylase (HDAC) unit is a cancer progression-related epigenetic regulator, which is overexpressed in hormone-refractory and metastatic prostate cancer (PCa). In our previous studies, we found a significantly increased MTA1 expression in a prostate-specific Pten-null mouse model. We also demonstrated that stilbenes, namely resveratrol and pterostilbene (Pter), affect MTA1/HDAC signaling, including deacetylation of tumor suppressors p53 and PTEN. In this study, we examined whether inhibition of MTA1/HDAC using combination of Pter and a clinically approved HDAC inhibitor, SAHA (suberoylanilide hydroxamic acid, vorinostat), which also downregulates MTA1, could block prostate tumor progression in vivo. We generated and utilized a luciferase reporter in a prostate-specific Pten-null mouse model (Pb-Cre+ ; Ptenf/f ; Rosa26Luc/+ ) to evaluate the anticancer efficacy of Pter/SAHA combinatorial approach. Our data showed that Pter sensitized tumor cells to SAHA treatment resulting in inhibiting tumor growth and additional decline of tumor progression. These effects were dependent on the reduction of MTA1-associated proangiogenic factors HIF-1α, VEGF, and IL-1ß leading to decreased angiogenesis. In addition, treatment of PCa cell lines in vitro with combined Pter and low dose SAHA resulted in more potent inhibition of MTA1/HIF-1α than by high dose SAHA alone. Our study provides preclinical evidence that Pter/SAHA combination treatment inhibits MTA1/HIF-1α tumor-promoting signaling in PCa. The beneficial outcome of combinatorial strategy using a natural agent and an approved drug for higher efficacy and less toxicity supports further development of MTA1-targeted therapies in PCa.

Changing Trends and Practices in Cytopathology.

OBJECTIVE: To explore the current and anticipated changes in the practice of cytopathology. STUDY DESIGN: The present review is based on a review of recent literature and an evaluation of the authors' personal experiences. RESULTS AND CONCLUSION: In recent years the practice of cytopathology, nationwide and in our institute, has witnessed a major change affecting gynecologic and nongynecologic cytology. There has been a decline in the number of Papanicolaou tests which has affected the utilization of cytotechnologists and provoked a reorganization of their work flow. The "need to do more with less" in the era of targeted therapy/personalized medicine has resulted in an increasing preference for needle core biopsy when performing a rapid on-site evaluation. We feel that this change is unavoidable. It is pertinent that cytopathologists as a group recognize this change and prepare themselves and the trainees not only to become adapt but also to use this as an opportunity to discover the yet unexplored world of cytology.

MTA1-activated Epi-microRNA-22 regulates E-cadherin and prostate cancer invasiveness.

We have previously shown that metastasis-associated protein 1 (MTA1), a chromatin remodeler, plays an important role in prostate cancer invasiveness, likely through regulation of epithelial-to-mesenchymal transition. Here, we identified miR-22 as an epigenetic-microRNA (Epi-miR) directly induced by MTA1 and predicted to target E-cadherin. Loss-of-function and overexpression studies of MTA1 reinforced its regulatory role in miR-22 expression. MiR-22 directly targets the 3'-untranslated region of E-cadherin, and ectopic overexpression of miR-22 diminishes E-cadherin expression. Overexpression of miR-22 in prostate cancer cells promotes cell invasiveness and migration. Meta-analysis of patient tumor samples indicates a positive correlation between MTA1 and miR-22, supporting their inhibitory effect on E-cadherin expression. Our findings implicate the MTA1/Epi-miR-22/E-cadherin axis as a new epigenetic signaling pathway that promotes tumor invasion in prostate cancer.

Poorly differentiated squamous cell carcinoma of the cervix with sarcomatoid differentiation: Report of a case with cytohistological correlation.

Sarcomatoid squamous cell carcinoma (SSCC) of the uterine cervix is a rare malignancy with uncertain pathogenesis and aggressive clinical behavior. The diagnosis of this tumor poses a challenge to the cytopathologist since accurate diagnosis is based on identification of two malignant components, that is, epithelial and sarcomatoid. Most cases usually lack the sarcomatoid component on Papanicolaou test (Pap test). Therefore, a poorly differentiated carcinoma or malignant neoplasm is the most often rendered diagnosis. To date, less than 20 cases have been reported. Most of these cases were diagnosed by histopathologic findings. To our knowledge, cytomorphologic findings of SSCC on a liquid-based Pap test, with utility of cell block sections, in recognition of the two components of tumor, with follow-up histopathologic correlation have not been described. A case of SSCC occurring in a 57-year-old postmenopausal woman, describing the cytologic features on a liquid-based Pap-test, histopathologic findings of subsequent cervical biopsy, differential diagnosis, and role of ancillary studies are illustrated and discussed. Diagn. Cytopathol. 2017;45:137-142. © 2016 Wiley Periodicals, Inc.