Immunohistochemical Analysis of the Expression of Cytokeratins in Acquired Cholesteatoma and Its Clinico-Radiological Correlation

Background and Objectives@#Cholesteatomatous chronic otitis media acquires epithelial proliferation and differentiation characteristics, which render it able to erode the underlying bone and cause complications. We attempt to characterize the cholesteatoma epithelium by observing the expression of cytokeratins (such as 34ße12, CK17, and CK13) and Ki67 among patients with cholesteatoma with different aggressiveness as compared to disease-free controls. @*Subjects and Methods@#In this prospective study (2017-2021), we enrolled all consenting consecutive patients with cholesteatomatous chronic otitis media. They were staged in accordance with the staging guidelines of the European Academy of Otology and Neurotology and the Japanese Otological Society. Bony external auditory canal (EAC) skin specimens of the patients undergoing tympanoplasty were chosen as controls. We did an immunohistochemical analysis of the cholesteatoma specimens and normal bony EAC controls by observing the expression of 34ße12, CK17, CK13, and Ki67 across the layers of the epithelium. Fisher’s exact test and chi-square test were used to evaluate any statistical significance between the cases and the controls, and the subgroups were made based on the clinical stage. @*Results@#An increased expression of CK17 (p<0.001), CK13 (p<0.03), and Ki67 (p<0.001) was observed in cholesteatoma specimens when compared to normal bony EAC controls. Also, there was a loss of expression of 34ße12 in a subset of cholesteatoma specimens, all of which showed full-thickness expression of CK13. There was no difference in the expression of cytokeratin among specimens from patients belonging to different subgroups based on clinical stage, age, sex, duration of ear symptoms, or type of hearing loss (conductive vs. sensorineural). @*Conclusions@#The majority of cholesteatoma specimens significantly overexpressed CK17, CK13, and Ki67 when compared to normal bony EAC skin controls, while a subset showed loss of expression of 34ße12, which provides some insight into its pathogenesis.

Primary pulmonary epithelioid inflammatory myofibroblastic sarcoma: a rare entity and a literature review

Epithelioid inflammatory myofibroblastic sarcoma (EIMS) is an aggressive subtype of inflammatory myofibroblastic tumor (IMT) harboring anaplastic lymphoma kinase (ALK) gene fusions and is associated with high risk of local recurrence and poor prognosis. Herein, we present a young, non-smoking male who presented with complaints of cough and dyspnoea and was found to harbor a large right lower lobe lung mass. Biopsy showed a high-grade epithelioid to rhabdoid tumor with ALK and desmin protein expression. The patient initially received 5 cycles of crizotinib and remained stable for 1 year; however, he then developed multiple bony metastases, for which complete surgical resection was performed. Histopathology confirmed the diagnosis of EIMS, with ALK gene rearrangement demonstrated by fluorescence in situ hybridization. Postoperatively, the patient is asymptomatic with stable metastatic disease on crizotinib and has been started on palliative radiotherapy. EIMS is a very rare subtype of IMT that needs to be included in the differential diagnosis of ALKexpressing lung malignancies in young adults.

Correlation of TTF-1 immunoexpression and EGFR mutation spectrum in non–small cell lung carcinoma

Background@#Thyroid transcription factor (TTF-1) is a diagnostic marker expressed in 75%–85% of primary lung adenocarcinomas (ACs). Activating mutations in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) gene is the most common targetable driver alteration in lung AC. Previous studies have shown a positive correlation between TTF-1 and EGFR mutation status. We aimed to determine the predictive value of TTF-1 immunoexpression for underlying EGFR mutation status in a large Indian cohort. @*Methods@#This retrospective designed study was conducted with medical record data from 2011 to 2020. All cases of primary lung AC and non–small cell lung carcinoma not otherwise specified (NSCLC, NOS) with known TTF-1 expression diagnosed by immunohistochemistry using 8G7G3/1 antibodies and EGFR mutation status diagnosed by quantitative polymerase chain reaction were retrieved, reviewed, and the @*results@#were analyzed. Results: Among 909 patient samples diagnosed as lung AC and NSCLC, NOS, TTF-1 was positive in 76.8% cases (698/909) and EGFR mutations were detected in 29.6% (269/909). A strong positive correlation was present between TTF-1 positivity and EGFR mutation status (odds ratio, 3.61; p < .001), with TTF-1 positivity showing high sensitivity (90%) and negative predictive value (87%) for EGFR mutation. TTF-1 immunoexpression did not show significant correlation with uncommon/dual EGFR mutations (odds ratio, 1.69; p = .098). EGFR–tyrosine kinase inhibitor therapy was significantly superior to chemotherapy among EGFR mutant cases irrespective of TTF-1 status; however, no significant differences among survival outcomes were observed. @*Conclusions@#Our study confirms a strong positive correlation between TTF-1 expression and common EGFR mutations (exon 19 deletion and exon 21 L858R) in advanced lung AC with significantly high negative predictive value of TTF-1 for EGFR mutations.

Correlation of TTF-1 immunoexpression and EGFR mutation spectrum in non–small cell lung carcinoma

Background@#Thyroid transcription factor (TTF-1) is a diagnostic marker expressed in 75%–85% of primary lung adenocarcinomas (ACs). Activating mutations in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) gene is the most common targetable driver alteration in lung AC. Previous studies have shown a positive correlation between TTF-1 and EGFR mutation status. We aimed to determine the predictive value of TTF-1 immunoexpression for underlying EGFR mutation status in a large Indian cohort. @*Methods@#This retrospective designed study was conducted with medical record data from 2011 to 2020. All cases of primary lung AC and non–small cell lung carcinoma not otherwise specified (NSCLC, NOS) with known TTF-1 expression diagnosed by immunohistochemistry using 8G7G3/1 antibodies and EGFR mutation status diagnosed by quantitative polymerase chain reaction were retrieved, reviewed, and the @*results@#were analyzed. Results: Among 909 patient samples diagnosed as lung AC and NSCLC, NOS, TTF-1 was positive in 76.8% cases (698/909) and EGFR mutations were detected in 29.6% (269/909). A strong positive correlation was present between TTF-1 positivity and EGFR mutation status (odds ratio, 3.61; p < .001), with TTF-1 positivity showing high sensitivity (90%) and negative predictive value (87%) for EGFR mutation. TTF-1 immunoexpression did not show significant correlation with uncommon/dual EGFR mutations (odds ratio, 1.69; p = .098). EGFR–tyrosine kinase inhibitor therapy was significantly superior to chemotherapy among EGFR mutant cases irrespective of TTF-1 status; however, no significant differences among survival outcomes were observed. @*Conclusions@#Our study confirms a strong positive correlation between TTF-1 expression and common EGFR mutations (exon 19 deletion and exon 21 L858R) in advanced lung AC with significantly high negative predictive value of TTF-1 for EGFR mutations.

Detection of Solitary Axillary Lymph Node Metastases from Hürthle Cell Carcinoma of the Thyroid on ¹⁸F-FDG PET/CT / 대한핵의학회잡지

Thyroid carcinoma is the most common neoplasm of endocrine malignancies. Differentiated thyroid carcinoma (DTC) constitutes 90% of the thyroid carcinomas, rest being medullary thyroid carcinoma (MTC), and anaplastic thyroid carcinoma (ATC). Distant metastases occur in up to 10% of patients with DTC. Metastases to axillary lymph nodes (ALN) are very rare. As per literature, only 25 cases have been reported. We report an unusual case of 47-year-old male with Hürthle cell carcinoma of the thyroid presenting with a solitary axillary lymph node metastasis 17 years after thyroidectomy, along with review of literature.

Detection of Solitary Axillary Lymph Node Metastases from Hürthle Cell Carcinoma of the Thyroid on ¹⁸F-FDG PET/CT / 대한핵의학회잡지

Thyroid carcinoma is the most common neoplasm of endocrine malignancies. Differentiated thyroid carcinoma (DTC) constitutes 90% of the thyroid carcinomas, rest being medullary thyroid carcinoma (MTC), and anaplastic thyroid carcinoma (ATC). Distant metastases occur in up to 10% of patients with DTC. Metastases to axillary lymph nodes (ALN) are very rare. As per literature, only 25 cases have been reported. We report an unusual case of 47-year-old male with Hürthle cell carcinoma of the thyroid presenting with a solitary axillary lymph node metastasis 17 years after thyroidectomy, along with review of literature.

Endobronchial Smooth Muscle Tumors: A Series of Five Cases Highlighting Pitfalls in Diagnosis

BACKGROUND: Primary endobronchial smooth muscle tumors (SMTs), which are extremely rare, include endobronchial leiomyomas and leiomyosarcomas. Clinically, SMTs present with signs and symptoms of bronchial obstruction, and lack specific radiological findings. Thus, histopathological examination is required for accurate diagnosis as well as for tumor grading. We examined the histomorphological and immunohistochemical features of endobronchial SMTs and highlighted pitfalls in diagnosis, particularly when using small biopsies. METHODS: Cases of primary endobronchial SMTs diagnosed at our Institute over the last 6 years (2012–2017) were retrieved from the departmental archives. Histopathological features and immunohistochemistry performed for establishing the diagnosis were reviewed. RESULTS: Five cases of SMTs occurring in endobronchial locations were identified. These included three cases of leiomyoma, and two cases of leiomyosarcoma. The age distribution of patients ranged from 13 to 65 years. Leiomyomas showed more consistent staining with smooth muscle markers (smooth muscle actin, desmin, and smooth muscle myosin heavy chain), while tumors of higher grade showed variable, focal staining, leading to erroneous diagnosis, especially on small biopsies. CONCLUSIONS: The diagnosis of endobronchial SMTs relies on histopathological examination, for both confirmation of smooth muscle lineage and determination of the malignant potential of the lesion. Appropriate immunohistochemical panels including more than one marker of smooth muscle differentiation are extremely valuable for differential diagnosis from morphological mimics, which is necessary for instituting appropriate management.

Thyroid Cytology in India: Contemporary Review and Meta-analysis

Fine-needle aspiration cytology (FNAC) is a screening test for triaging thyroid nodules, aiding in subsequent clinical management. However, the advantages have been overshadowed by the multiplicity of reporting systems and a wide range of nomenclature used. The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) was formulated in 2007, to give the world a uniform thyroid cytology reporting system, facilitating easy interpretation by the clinicians. Here, we review the status of thyroid FNAC in India in terms of various reporting systems used including a meta-analysis of the previously published data. An extensive literature search was performed using internet search engines. The reports with detailed classification system used in thyroid cytology were included. The meta-analysis of published data was compared with the implied risk of malignancy by TBSRTC. More than 50 studies were retrieved and evaluated. TBSRTC is currently the most widely used reporting system with different studies showing good efficacy and interobserver concordance. Ancillary techniques have, as of now, limited applicability and acceptability in thyroid cytology in India. Twenty-eight published articles met the criteria for inclusion in the meta-analysis. When compared with TBSRTC recommendations, the meta-analysis showed a higher risk of malignancy for categories I and III. Thyroid FNAC is practiced all over India. TBSRTC has found widespread acceptance, with most institutions using this system for routine thyroid cytology reporting. However, reasons for a high malignancy risk for categories I and III need to be looked into. Various possible contributing factors are discussed in the review.

p40 in metastatic pulmonary trophoblastic tumour: potential diagnostic pitfall on histopathology

p40, one of the two isomers of p63, is nowadays widely used for diagnosis of squamous cell carcinoma, especially in subtyping non-small cell carcinoma on lung biopsies. We describe a case in which lung tumour was misdiagnosed as squamous cell carcinoma due to p40 immunopositivity. A 36-year-old lady presented with cough and left sided chest pain of 2 months duration. Chest imaging revealed a lesion in left lower lobe of the lung and biopsy was suggestive of squamous cell carcinoma. However, past history revealed amputation of great toe for non-healing discharging ulcer which on histopathology was diagnosed as choriocarcinoma. She also had a history of hysterectomy five years ago, details of which were not available. Post-amputation β-hCG levels were high and she had been treated with multimodality chemotherapy for choriocarcinoma. She had good response to chemotherapy initially, however became resistant later on. Review of the lung biopsy in the light of the past history along with extensive literature review led to the final diagnosis of metastatic trophoblastic tumour to lung. Hence, awareness that p40 immunopositivity can be seen in trophoblastic tumours is essential to avoid misdiagnosis, especially in sites like the lung where squamous cell carcinoma is common.

Acid-Fastness of Histoplasma in Surgical Pathology Practice

BACKGROUND: Histoplasmosis (HP) is diagnosed by visualizing intracellular microorganisms in biopsy and/or culture. Periodic-acid Schiff (PAS) and Gomori methenamine silver (GMS) staining methods are routinely used for identification. The acid-fast property of Histoplasma was identified decades ago, but acid-fast staining has not been practiced in current surgical pathology. Awareness of the acid-fast property of Histoplasma, which is due to mycolic acid in the cell wall, is important in distinguishing Histoplasma from other infective microorganisms. Here, we examined acid-fastness in previously diagnosed cases of Histoplasma using the Ziehl-Neelsen (ZN) stain and correlated those findings with other known fungal stains. METHODS: All cases diagnosed as HP were retrieved and reviewed along with ZN staining and other fungal stains. We also stained cases diagnosed with Cryptococcus and Leishmania as controls for comparison. RESULTS: A total of 54 patients ranging in age from 11 to 69 years were examined. The most common sites of infection were the skin, adrenal tissue, and respiratory tract. Of the total 43 tissue samples, 20 (46.5%) stained positive with the ZN stain. In viable cases, a significant proportion of microorganisms were positive while necrotic cases showed only rare ZN-positive yeasts. In comparison to PAS and GMS stains, there was a low burden of ZN-positive yeasts. Cryptococcus showed characteristic ZN staining and all cases of Leishmania were negative. CONCLUSIONS: Although the morphology of fungal organisms is the foundation of identification, surgical pathologists should be aware of the acid-fast property of fungi, particularly when there is the potential for confusion with other infective organisms.