Turkish Journal of Pathology - 2023; 39(2)

Whole Slide Images in Artificial Intelligence Applications in Digital Pathology: Challenges and Pitfalls

Kayhan BASAK, Kutsev Bengisu OZYORUK, Derya DEMIR — 2023-05-01

The use of digitized data in pathology research is rapidly increasing. The whole slide image (WSI) is an indispensable part of the visual examination of slides in digital pathology and artificial intelligence applications; therefore, the acquisition of WSI with the highest quality is essential. Unlike the conventional routine of pathology, the digital conversion of tissue slides and the differences in its use pose difficulties for pathologists. We categorized these challenges into three groups: before, during, and after the WSI acquisition. The problems before WSI acquisition are usually related to the quality of the glass slide and reflect all existing problems in the analytical process in pathology laboratories. WSI acquisition problems are dependent on the device used to produce the final image file. They may be related to the parts of the device that create an optical image or the hardware and software that enable digitization. Post-WSI acquisition issues are related to the final image file itself, which is the final form of this data, or the software and hardware that will use this file. Because of the digital nature of the data, most of the difficulties are related to the capabilities of the hardware or software. Being aware of the challenges and pitfalls of using digital pathology and AI will make pathologists' integration to the new technologies easier in their daily practice or research.

25-Year Storage of Human Choroid Plexus in Methyl Salicylate Preserves Its Antigen Immunoreactivity

2023-05-01

Objective: Immunohistochemical investigation of archival histological material is a serious problem, since long-term storage of biological tissues, most often in formalin, leads to a loss of antigenic properties. However, the biological material can also be stored in the clearing agent methyl salicylate. The aim of this study was to assess the antigenicity of the human choroid plexus after extra long-term storage in methyl salicylate. Material and Method: The study was performed on samples of fixed human choroid plexus (occasionally with attached neighboring pineal gland) stored in either methyl salicylate or paraffin blocks for 25 years. Chromogenic and fluorescence immunohistochemistry of vimentin, GFAP, type IV collagen, β-catenin, α-smooth muscle actin, von Willebrand factor, CD68, mast cell tryptase, TMEM119, and synaptophysin was carried out. Results: The storage of human choroid plexus in methyl salicylate for 25 years does not impair its histomorphology and preserves the properties of all the antigens assessed, which makes their immunohistochemical visualization possible using both light and fluorescence microscopy. Additionally, we found that long-term storage of human choroid plexus in methyl salicylate does not cause an increase in autofluorescence. Conclusion: Methyl salicylate can be recommended as a medium for long-term storage of biological tissue, as it provides excellent brain tissue preservation and retains its antigenic properties for up to 25 years.

Development of Glioblastoma from Stem Cells to a Full-Fledged Tumor

2023-05-01

Objective: IDH wild-type glioblastomas (GBM) are one of the most malignant and complex tumors for treatment. The urgent question of new therapeutic and diagnostic tools searching should be resolved based on cellular and molecular pathogenesis mechanisms, which remain insufficiently studied. In this study, we aimed to investigate GBM pathogenesis. Material and Method:/b> Using the isolation of different GBM cell populations and the cell cultures, animal models, and molecular genetic methods, we tried to clarify the picture of GBM pathogenesis by constructing a projection from different glioma stem cells types to an integral neoplasm. Results: We have shown a potential transformation pathway for both glioma stem cells and four definitive cell populations during gliomagenesis. Moreover, we have characterized each population, taking into account its place in the pathogenetic continuum, with a description of the most fundamental molecular and functional properties. Conclusion: Finally, we have formed a complex holistic concept of the pathogenetic evolution of GBM at the cell-population level by integrating our results with the data of the world literature.

Histoplasmosis of the Head and Neck Region Mimicking Malignancy: A Clinic-Pathological Predicament

2023-05-01

Objective: Histoplasmosis is a systemic, deep mycotic infection caused by Histoplasma capsulatum. Disseminated histoplasmosis (DH) is synonymous with HIV seropositive immunocompromised individuals; however, isolated histoplasmosis involving the head and neck mucosal sites mimicking malignancy is a clinical predicament. The result, in a superficial biopsy with marked pseudoepitheliomatous hyperplasia (PEH), in a tertiary care cancer center where the number of squamous carcinomas far outnumber the infectious diseases, could be catastrophic. Material and Method: The archives of a tertiary care cancer hospital were searched (2010-2019) for cases of histoplasmosis involving the head and neck mucosal sites in HIV non-reactive patients. Results: Six cases of isolated head and neck histoplasmosis were seen in biopsies from 4 men and 2 women, with an age range of 46-72 years. Three of these patients suffered from chronic illnesses. The most common site involved was the larynx (vocal cords) in three cases, two cases were involving lips, and one involving the tongue. The biopsies were reviewed in-house with a clinical diagnoses of malignancy in all and an outside biopsy diagnosis of �squamous cell carcinoma� in 2 cases. The important histological findings in the biopsy were PEH (3 cases), granulomas (2 cases), lymphoplasmacytic inflammation (all cases). Eosinophils were conspicuous by their absence. Intracellular histoplasma was seen in all cases, albeit to varying density, which was confirmed with GMS stain. Conclusion: A high index of suspicion, meticulous history taking by oncologists, and appropriate distinction of PEH from neoplastic squamous proliferation by pathologists in superficial biopsies and an apropos deeper wedge biopsy are essential to clinch the correct diagnosis.

Impact of COVID-19 Pandemic on Pathology Residency Program: An Experience from India

2023-05-01

Objective: To study the impact of the COVID-19 pandemic on pathology residents through a questionnaire-based survey. Material and Method: We designed a Google survey questionnaire with 20-questions and distributed it to the pathology residents across India via e-mail and WhatsApp. All the responses collected were analysed using appropriate statistical methods. Results: We received a total of 81 responses. The majority (n=55, 68.8%) of the residents were aged 26-30 years with a male-female ratio of 1:2.2. Residents reported a significant decrease in classes as compared to pre-covid times. However, most institutions (90%) shifted to the virtual method for various teaching sessions. About 94.7% of the residents felt a fall in the quality of training due to Covid. A significant number of junior residents (76.92%) reported an inability to complete the target thesis enrolment. The residents saw a substantial decrease in the number of peripheral smears, bone marrow, cytology, and histopathology cases compared to pre-Covid times (p value <0.001 for all). An overwhelming 83.8% of the pathology residents were posted for COVID-19 duties. About 48.8% turned Covid positive. About 77.5% (n=62) of residents felt that the necessary training period would be extended. Conclusion: The COVID-19 pandemic has immensely affected the training and teaching of pathology residents in India. Similarly, this pandemic must have affected pathology residents all across the globe. Therefore, institutions can consider offering an extended period of up to one year, depending upon residents� requests.

Analysis of SMARCA4 and SMARCA2 Loss in Lung Sarcomatoid Carcinomas

Halide Nur URER, Nurcan UNVER, Neslihan FENER — 2023-05-01

Objective: Sarcomatoid carcinomas of the lung are a group of aggressive tumors. It has been reported that losses of SMARCA4 and SMARCA2, which play a role in the repair and remodeling of chromatin, contribute to the initiation, progression, and differentiation of neoplasms. The aim of our study was to examine SMARCA4 and SMARCA2 profiles in sarcomatoid carcinomas of the lung. Material and Method: We screened pleomorphic carcinomas (PCs), carcinosarcomas (CSs), and pulmonary blastomas (PBs). The loss of SMARCA4 and SMARCA2 expression in the tumors was evaluated using immunohistochemical methods. The tumors were also examined to determine immunophenotype, histological tumor diagnosis, surgical resection, tumor histological component, largest tumor diameter, and lymph node metastasis status. Results: Sixty-nine cases were screened, of which 84% were PCs, 13% were CSs, and 2.8% were PBs. In PCs components, 84.4% were biphasic and 15.5% were monophasic. The PCs showed the most frequent loss of SMARCA4 (25.8%) and SMARCA2 (44.8%). A loss of SMARCA4 and SMARCA2, respectively, was detected in 14.2% and 24.4% in both components of biphasic PCs; 12.2% and 14.2% in the sarcoma component of biphasic PCs; 0% and 8.1% in the carcinoma component of biphasic PCs; 22.2% and 33.3% in monophasic PCs; 0% and 22.2% in both components of CSs; and 0% and 22.2% in the sarcoma component of CSs. Conclusion: These findings demonstrate a loss of expression of SMARCA4 and SMARCA2 in pulmonary sarcomatoid carcinomas. Loss of the SMARCA complex may be caused by the heterogeneous morphological profile of sarcomatoid carcinomas, independent of tumor histopathological parameters.

A Rare Case of A Low-Grade Inflammatory Leiomyosarcoma/Histiocyte-Rich Rhabdomyoblastic Tumor in the Neck of An Adolescent Male

2023-05-01

Inflammatory leiomyosarcoma (LMS) is a newly included rare tumor entity in the group of smooth muscle tumors in the recent WHO classification. Recent studies have shown skeletal muscle expression within this tumor and its proximity with histiocyte-rich rhabdomyoblastic tumor (HRRT). A 17-year-old male presented with a soft tissue lump over the back of his neck of one-year duration. Radiologically, a lesion measuring 5.9 cm in the largest dimension was seen, extending from the skull base up to the C2 vertebral level, abutting the occipital bone. The initial biopsy was reported as a fibrohistiocytic tumor at the referring laboratory. A microscopic review of the sections from the initial biopsy and subsequent resection revealed a well-circumscribed, cellular tumor composed of plump spindle and polygonal-shaped tumor cells with relatively bland nuclei, moderate to abundant eosinophilic cytoplasm and numerous interspersed histiocytes, including foam cells and lymphocytes. Immunohistochemically, the tumor cells were positive for desmin, MYOD1 and SMA, focally positive for myogenin, while negative for h-caldesmon, SOX10 and S100P. A diagnosis of inflammatory leiomyosarcoma/HRRT was offered. Subsequently, the tumor was tested for MYOD1 (L122R) mutation and was found to be negative. The patient underwent adjuvant radiation therapy and is free-of-disease at 12 months post-treatment. This case constitutes an extremely rare case of an inflammatory LMS/HRRT, identified in the neck region. This tumor should be differentiated from its close mimics, such as a spindle cell/sclerosing rhabdomyosarcoma, as the latter is treated more aggressively, including with chemotherapy, given its relatively poor prognosis.

Neuroendocrine Tumor of the Fallopian Tube and Serous Adenocarcinoma of the Ovary: Multicentric Primary Tumors

2023-05-01

Neuroendocrine tumors (NETs) comprise a large group of tumors that are most often localized in the gastrointestinal tract and lungs. They are rarely found in the organs of the female reproductive tract; such NETs are primarily localized in the ovaries. We present a case of multicentric primary low-grade NET of the fallopian tube and high-grade ovarian serous adenocarcinoma. In both tumor regions, the histotypes of neoplasms were determined by morphological and immunohistochemical investigations. The NET of the fallopian tube was diffusely positive for chromogranin A and CD56, but wild type for p53 and negative for CK7, CK20, and ER; Ki-67 expression was observed in 3% of the neoplastic cells. The ovarian serous adenocarcinoma was positive for CK7 and ER, mutant for p53, but negative for chromogranin A, CK20, and CD56; Ki-67 expression was observed in 45% of the tumor cells. These results support the possibility that NET can occur in the female reproductive tract and coexist with other malignant tumors.

Correction: Development of Glioblastoma from Stem Cells to a Full-Fledged Tumor

2023-05-01