Turkish Journal of Pathology - 2020; 36(3)

How to Set Up a Molecular Pathology Lab: A Guide for Pathologists

An�l AYSAL, Bur�in PEHLIVANO�LU, S�meyye EKMEKCI, Bet�l G�NDO�DU — 2020-09-01

In today�s pathology practice, pathologists combine molecular tests with conventional histopathological methods. Pathology laboratories should therefore be designed and operated in accordance with the requirements of molecular testing procedures. While the specifics of the requirements may vary depending on the spectrum of the tests that will be performed, there are several basic criteria that need to be fulfilled for standardization. Adequate space, appropriate equipment and qualified personnel are required to establish a molecular pathology laboratory. One of the most important points that should be taken into consideration while designing a molecular pathology laboratory is to create a plan to prevent contamination. As molecular diagnosis has a major role in treatment decisions, the management of the molecular pathology laboratory is of utmost importance. In this review, the criteria required to establish an optimal molecular pathology laboratory will be reviewed.

The Contribution of Additional Sampling in Cholecystectomy Materials: A Multicenter Prospective Study

2020-09-01

Objective: Cholecystectomy materials are frequently encountered in routine practice. The aim of this study was to determine the true frequency of gallbladder lesions, the diagnostic consistency, and standardization of reports after macroscopic sampling and microscopic evaluation based on previously defined criteria. Material and Method: 14 institutions participated in the study within the Hepato-Pancreato-Biliary Pathology Study Group. Routinely examined cholecystectomies within the last year were included in the study in these institutions. Additional sampling was performed according to the indications and criteria. The number of blocks and samples taken in the first macroscopic examination and the number of blocks and samples taken in the additional sampling were determined and the rate of diagnostic contribution of the additional examination was determined. Results: A total of 5,244 cholecystectomy materials from 14 institutions were included in the study. Additional sampling was found to be necessary in 576 cases (10.98%) from all institutions. In the first macroscopic sampling, the mean of the numbers of samples was approximately 4 and the number of blocks was 2. The mean of the numbers of additional samples and blocks was approximately 8 and 4, respectively. The diagnosis was changed in 144 of the 576 new sampled cases while the remaining 432 stayed unaltered. Conclusion: In this study, it was observed that new sampling after the first microscopic examination of cholecystectomy materials contributed to the diagnosis. It was also shown that the necessity of having standard criteria for macroscopic and microscopic examination plays an important role in making the correct diagnosis.

The Clinicopathological Significance of Basal Markers in Early-Stage Invasive Carcinoma of No Special Type of the Breast

Fikret DIRILENO�LU, Demet ARIKAN ETIT, Halil TA�KAYNATAN, Ferhan ELMALI — 2020-09-01

Objective: Basal markers [cytokeratin 5/6 (CK5/6) and epidermal growth factor receptor (EGFR)] are used in identifying the basal-like breast carcinoma subtype, which is associated with a poor prognosis. However, the clinicopathological significance in early-stage invasive carcinoma of no special type (IC, NST) has not been well established. Material and Method: In a five-year period, 133 female patients with early-stage IC, NST with a median follow-up time of 89 months were included. The immunohistochemistry-based molecular subtypes were identified according to ASCO/CAP guidelines in 2013. The cutoff values for basal positivity were determined as 10% for each marker. Results: Basal positivity was recorded in 83.3% (5/6) of triple-negative breast cancers, 50% (2/4) of HER2-enriched, 18.6% (13/70) of luminal B, and 8.3% of luminal A (4/48) subtype. CK5/6 and EGFR positivity were significantly associated with ER negativity (p < 0.001). EGFR positive cases were significantly associated with PR negativity and HER2 positivity compared to negative cases. However, basal positivity was not associated with the patient outcome (p = 0.006 and p = 0.004, respectively). Conclusion: Basal positive IC, NSTs were associated with hormone receptor negativity and HER2 overexpression; these patients would therefore be less likely to respond to hormonotherapy and more likely to benefit from anti-HER2 treatment as well as dual-kinase inhibitors. The lack of standardization of the definition of basal marker positivity may contribute to the conflicting results of prognostic studies. Hence, further studies focusing on developing a standard protocol for determining basal marker positivity are needed not only for IC, NST but also for other histological types of breast cancer.

Efficiency of Cytology Samples for PD-L1 Evaluation and Comparison with Tissue Samples

�brahim KULA�, Asl� AYDIN, P�nar BULUTAY, P�nar FIRAT — 2020-09-01

Objective: Lung cancer is the leading cause of cancer-related death. PD-L1 blockers have become a first-line option for advanced non-small cell lung cancer (NSCLC) patients. Guidelines require the assessment of PD-L1 expression by immunohistochemistry. Although tissue samples are widely used, cytologic samples could be an alternative. In this study, we compared cytologic samples with tissue samples for PD-L1 evaluation in NSCLC cases. Material and Method: Ko� University Hospital, Department of Pathology Laboratory Information System was scanned for all PD-L1 tests performed on NSCLC cases, either on tissue samples or cell blocks. The type of the biopsy/aspiration procedure, the tumor type, patient demographics, and the percentage of PD-L1 positive tumor cells were recorded. A total of 73 tissue samples and 49 cell blocks were found to be eligible for the study. Results: The PD-L1 positivity score was at least 1% in 44 of 73 samples of the tissue group and 19 of 49 samples of the cell block group. Tissue samples showed significantly higher positivity compared to the cell blocks (p=0.020). Comparing the frequency of cases with ≥50% positivity showed no statistically significant difference. A comparison of PD-L1 positivity rates of only the small biopsies and cell blocks also showed no significant difference. Conclusion: Although they harbor a limited number of tumor cells, cell blocks prepared from cytologic samples are good alternatives for PD-L1 testing. However, large resections should be used for PD-L1 evaluation whenever possible since even 1% positivity may affect the treatment decision.

Male Breast Cancer: Clinicopathological, Immunohistochemical and Radiological Study

Bermal HASBAY, Filiz AKA BOLAT, H�seyin �zg�r AYTA�, Murat KU�, Ay�in POURBAGHER — 2020-09-01

Objective: To evaluate the pathological and radiological features, immunohistochemical profile and treatment methods of primary male breast carcinoma cases diagnosed at our center. Material and Method: The pathology archive between 2006 and 2019 was reviewed and the data of 27 male patients diagnosed as primary breast cancer were retrospectively evaluated. Results: The age of the patients ranged between 40-86 years. The left breast was involved in 17 patients. The mean tumor diameter was 2.35 � 1.09 cm. Of the 27 cases, 8 were dead and 19 were alive. The mean follow-up duration was 37.45 � 24.84 months. The mean estimated life expectancy was 65�14.7 months. The most common complaint was a swelling in the breast. The time interval between the onset of complaints and admittance to hospital ranged from three months to two years. The most common histopathological diagnosis was invasive carcinoma - no special type. The most common surgical procedure was mastectomy with lymph node dissection. Nine patients had metastatic lymph nodes. In terms of the hormone profiles, 24 were Estrogen receptor positive, 21 were Progesterone receptor positive and six were Her2/neu positive. Three patients had triple-negative tumors. Conclusion: Male breast carcinoma is a rare disease but its frequency has been increasing recently. As breast cancer is more commonly attributed to women, the diagnosis is usually delayed until later stages in males. Public awareness should therefore be increased and breast cancer should be considered in the differential diagnosis especially in the presence of breast swelling and complaints related to the breast skin so that the appropriate biopsy can be obtained without delay.

Evolution of Telepathology: A Comprehensive Analysis of Global Telepathology Literature Between 1986 and 2017

Engin �ENEL, Y�lmaz BA� — 2020-09-01

Objective: Telepathology is an application of telemedicine providing remote evaluation and consultation of digital pathology images and can be used for educational or experimental purposes. Bibliometrics is a statistical discipline investigating publication patterns and trends in a certain academic field. Although bibliometric and scientometric studies are becoming increasingly popular, the relevant literature contains only one limited article related to telepathology. The aim of our study was to perform a holistic bibliometric analysis of the telepathology literature. Material and Method: Since the first article on telepathology was published in 1986, we included all indexed articles retrieved from Web of Science databases between 1986 and 2017. Results: We found that the USA covering 43.01% of all literature was the leading country in the telepathology field and was followed by Germany, Italy and the UK (n=120, 90 and 83, respectively). The countries with the most contributions were located in the continents of Europe and North America. The most productive source titles were Human Pathology, Journal of Telemedicine and Telecare, and Modern Pathology. Harvard University ranked first with 59 articles. The most commonly used keywords of the telepathology literature were �telepathology�, �telemedicine�, �digital pathology�, �virtual microscopy� and �telecytology�. We noted that all of the ten countries with the most contributions were in the developed category of UN classification and all twenty of the most productive institutions were from developed countries. Conclusion: We suggest that researchers from developing and least developed countries should be encouraged to carry out novel studies since telemedicine is a required and promising technology for rural developing or least developed areas in which access to health care is difficult.

Diagnostic Utility of Immunohistochemical Expressions of IMP3 Versus DOG1 and p63 in Salivary Gland Tumors

Taiseer R. IBRAHIM, Mona Mostafa AHMED, Abdelmonem Awad HEGAZY — 2020-09-01

Objective: The diverse site of origin and classification complexity of salivary glands tumors increase difficulties in their diagnosis. This study aimed to evaluate the specificity and diagnostic ability of immunohistochemical expressions of IMP3 versus DOG1 and p63 in cases of such tumors. Material and Method: Thirty paraffin-embedded salivary gland tumors were obtained from the Pathology Department Archive. Their diagnosis was confirmed. The specimens were then re-classified and evaluated using the IMP3, DOG1 and p63 immunohistochemical markers. Results: There were 8 pleomorphic adenoma (PA), 12 mucoepidermoid carcinoma (MEC) and 10 adenoid cystic carcinoma (ADC) cases. All 12 MECs (100%) were IMP3 positive, while 30% of ADCs and only 25% of PAs were positive for IMP3. There was a statistically significant relationship between salivary gland tumors and IMP3 immunostaining (P =0.03). As regards to DOG1 results, 12.5% of PAs showed variable luminal positive immunostaining and 40% of ADCs showed weak luminal and abluminal immunostaining while 16.7% of MEC showed cytoplasmic staining. On the other hand, all ADCs (100%) showed moderate p63 reactivity in the nuclei of abluminal cells. All MEC cases (100%) were also p63-positive, showing a strong diffuse nuclear reactivity. A statistically significant relationship was noticed between salivary gland tumors and p63 immunostaining (P <0.05). Conclusion: IMP3 is more sensitive for diagnosis of MEC than ADC. p63 is statistically significant in diagnosing salivary gland tumors (MEC and ADC). On the other hand, DOG1 staining is not sensitive in diagnosis of studied malignant salivary gland tumors, limiting its diagnostic utility.

Morphologic Spectrum of Undetermined Causes of Hemoptysis- A Pathologist�s Role

Nidhya GANESAN, Umamaheswari GURUSAMY — 2020-09-01

Objective: Hemoptysis is the expectoration of blood or blood-streaked sputum from the tracheobronchial tree. The etiology may derive from nonneoplastic conditions such as infections, chronic pulmonary diseases, and vasculitis or neoplastic causes. Sometimes a definitive cause for hemoptysis cannot be found after ample diagnostic workup. The role of biopsy in such cases is to help the clinician in arriving at the final diagnosis. Diffuse alveolar hemorrhage is the main histopathological finding in hemoptysis and it appears with diffuse chest infiltrates radiologically. Material and Method: A retrospective study of 2 years duration was conducted to identify the morphological spectrum of diseases presenting with hemoptysis. A total of 243 lung biopsies obtained by various methods were retrieved in this study period and 20 cases with hemoptysis of undetermined etiology were detected. Results: Based on imaging and histopathology findings, the etiological causes of hemoptysis were divided into hemoptysis with and without capillaritis or due to tumor/tumor-like lesions and due to miscellaneous conditions. The most common etiology was vasculitis followed by infections. Conclusion: Histopathology helps to detect the etiology, particularly in cases of hemoptysis due to non-immunologic causes. In immunologic cases, histopathological findings may support the diagnosis in correlation with the clinical/imaging features.

Pneumocystis Jirovecii Pneumonia in Newly Diagnosed HIV Infection: A Challenging Case Report

Selin KESTEL KAYIK, Elif ACAR, Leyla MEM�� — 2020-09-01

Pneumocystis jirovecii is a potentially life-threatening opportunistic pathogen particularly affecting the lungs, mainly in immunosuppressed individuals and HIV-infected patients with a low CD4 cell count. A 50-year-old man presented with a 1-week history of pleuritic chest pain and fever. He was also hypoxic with oxygen saturation of 86% on room air. Detailed clinical history revealed that he had fatigue, dyspnea, night sweats, generalized bone pain and a loss of about 10 kg in weight over the past six months without intention. Chest imaging showed diffuse bilateral infiltrates. Diagnostic bronchoscopy was performed. Transbronchial biopsy and bronchoalveolar lavage were received simultaneously. The presence of P. jirovecii was suspected in hematoxylin-eosin-stained slides, and Gomori�s methenamine silver stain was used to confirm the diagnosis. A blood test revealed dyslipidemia, hypothyroidism, increased plasma levels of the gonadotropins and positive HIV antibodies with a CD4+ cell count of 48/μL. CMV co-infection was found with CMV viral load of 6738 copies/ml in plasma. Herein, we present a case with Pneumocystis jirovecii pneumonia (PCP) that led to a new diagnosis of Human immonudeficiency virus. As in our case, diagnosis of disease through the pathological examination of tissues (biopsy samples) or bodily fluids could lead to the recognition of an unrevealed HIV-infection.

Uterine Leiomyoma with Massive Lymphoid Infiltrate in a Patient with History of Assisted In-Vitro Fertilization

2020-09-01

Uterine leiomyomas are the most common benign tumors of the gynecological tract. Massive lymphocytic infiltration has been reported rarely in uterine leiomyomas and it has been described as a pathogenetic correlation with gonadotropin-releasing hormone agonists. Uterine leiomyomas with massive lymphoid infiltration have to be differentiated from non-Hodgkin lymphomas. We report a case of a woman without a history of gonadotropin-releasing hormone agonist treatment, who presented with a uterine leiomyoma that increased in size after the procedure of assisted in-vitro fertilization, and associated with massive nodular lymphoid infiltrate simulating, morphologically, a non-Hodgkin lymphoma. Uterine leiomyoma with massive lymphocytic infiltration is a very rare entity, probably of reactive significance, which has to be differentiated from diseases that need a systemic therapeutic approach.

Sirenomelia (Mermaid Syndrome): A Case Report

�irin K��K, �zzet G�ker K��K — 2020-09-01

Sirenomelia, which is also known as mermaid syndrome and characterized by the fusion of the lower extremities, is the most severe form of caudal regression syndrome and one of the rare and lethal congenital malformations. The anomalies that might be seen in this syndrome include pelvic-sacral dysplasia, genital anomalies, bilateral pelvic renal fusion accompanied by renal dysplasia, colon atresia, unilateral umbilical artery, and imperforated anus. The incidence of sirenomelia is 0.8-1 cases in 60,000-100,000 deliveries and the male/female ratio is 2.7-3:1. The case reported in the present study was a 13-week-old male fetus 30 g in weight with a macerated appearance. The upper extremities had a relatively normal appearance but the lower extremities were conjoined and there was a single lower extremity consisting of conjoined feet and toes. In the face, the nasal bridge was sunken, the ears had a low position, and there were cleft palate and cleft lip. Examination of the external genital organs revealed that the penile part was in the anal region. There was no anus opening. The crown-rump length was 8.5cm, the heel-toe length was approx. 1cm, and the rump-heel length was approx. 3.7cm. There were none of the two kidneys, ureter, bladder, urethra, or rectum. In the umbilical cord, there were 2 venous structures, one of which was the artery. Perivillous congestion and hyperemia, perivillous calcification, deciduitis, and focal infarct regions were observed in placental tissues. This report aims to discuss this very rare case together with the literature.

Small Cell Carcinoma of Ovary, Hypercalcemic Type (Malignant Rhabdoid Tumor of Ovary) with Loss of SMARCA4 (BRG1) Expression: Report of Two Cases

2020-09-01

Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) / malignant rhabdoid tumor of the ovary (MRTO) is a rare tumor affecting young women. It is frequently misdiagnosed due to overlapping morphological and immunohistochemical features with many other ovarian tumors. The prognosis of the tumors is very poor; hence an accurate diagnosis is of utmost importance. Recently, the loss of BRG1 protein by immunohistochemistry has been shown to be a useful diagnostic marker. We present here two cases of SSCOHT/MRTO, in young women 22 and 32 years of age, where several differential diagnoses were considered on morphology and immunohistochemistry but were confirmed as SCCOHT/MRTO by the demonstration of loss of BRG1. As the prognosis of SCCOHT is very dismal, and accurate diagnosis is of necessity, we recommend the inclusion of BRG1 immunohistochemistry in the diagnostic armamentarium of poorly differentiated ovarian tumors, particularly in young adults.

Lipofibromatosis: A Rare Diagnosis on Fine Needle Aspiration Cytology

Arti KHATRI, Nidhi MAHAJAN, Mamta SENGAR, Anil AGARWAL — 2020-09-01

Lipofibromatosis is a recently recognized slow growing rare pediatric tumor. Paucity of its cytological description in the literature leads to its pre operative misdiagnosis and further incomplete management. A twelve-month-old female presented with a rapidly progressive mass in the right thigh and buttock region. On examination, the mass was huge and involved the medial, posterior and lateral aspects of the thigh. The cytological smears showed mature adipocytes with few spindled out cells. FNA was reported as a lipoma, corroborating with the radiological presumptive diagnosis. However, histopathological and immunohistochemical features favoured a diagnosis of Lipofibromatosis. The cytological smears were reviewed and a cyto-histo correlation was established. The diagnosis of Lipofibromatosis rests upon classical cytological features in a clinically and radiologically suggestive picture. An early and accurate diagnosis if established can help the surgeon plan excision with wider margins as incomplete excision is associated with a high rate of recurrence.

Signet-Ring Cell Morphotype in Lung Carcinoma

Adriana HANDRA-LUCA — 2020-09-01