Turkish Journal of Pathology - 2019; 35(1)

Differential Expression of EGFR-1, MMP-3, and MMP-9 in Spontaneous Abortions, Induced Abortions, and Tubal Pregnancies

Mahi BALCI , G�lhan �ZDEMIR — 2019-01-01

Objective: The purpose of our study was to assess trophoblastic and uterine sufficiency in miscarriage pathogenesis with immunohistochemical methods and to determine if they could be used as a screening tool for the risk of miscarriage in the future. Material and Method: Placental tissue specimens that were comprised of 20 spontaneous abortions, 23 voluntarily terminated (induced) abortions, and 12 tubal pregnancies were included in this study. Trophoblastic cells and implantation area were evaluated for staining with EGFR-1, MMP-3, and MMP-9 by immunohistochemistry. Results: EGFR-1 expression was more intense and diffuse in decidual cells in the placental bed of spontaneous abortion specimens; this difference was statistically significant (P=0.004). MMP-3 expression was markedly increased in villous and extravillous trophoblastic cells in induced abortions; the difference between the groups was found to be statistically significant (P values ranged from < 0.01 to 0.005). MMP-9 expression tended to be higher in spontaneous abortion and tubal pregnancy specimens, and the results were statistically significant as P values were lower than 0.01. Conclusion: Higher EGFR-1 expression in the decidual tissue of spontaneous abortion specimens suggests that EGFR-1 triggers the migration of extravillous trophoblasts, leading to their destructive invasion. Similarly, MMP-9 immunopositivity might be indicative of aggressive invasion contributing to spontaneous abortion pathogenesis. Relatively high levels of MMP-3 expression in induced abortion specimens used as a control group might be a predictor of successful implantation, whereas its decreased expression might be indicative of risk for pregnancy loss.

Clinical Significance of Granulation Pattern in Corticotroph Pituitary Adenomas

2019-01-01

Objective: The granulation pattern of pituitary tumors may be important to predict tumor behavior, treatment outcomes, and recurrences. Therefore, we compared densely granulated corticotroph tumor (DGCT) and sparsely granulated corticotroph tumor (SGCT) in terms of clinicopathologic findings. Material and Method: A total of 41 patients (31 females/10 males) were assessed in the study. The granulation patterns were detected by Periodic Acid-Schiff (PAS) and adrenocorticotropic hormone (ACTH) immunoreactivity. Diffuse and strong staining by PAS and ACTH were identified as DGCT, whereas faint staining by PAS and focal, weak staining by ACTH were identified as SGCT. Perinuclear ring-like patterns with low molecular weight keratin were identified as Crooke�s cell tumors. DGCTs and SGCTs were compared in terms of clinical findings and treatment outcomes. Results: The majority of the patients (71%) had DGCTs (n=29); whereas 24% of the patients had SGCTs (n=10) and 5% of the patients had Crooke�s cell tumors (n=2). DGCTs and SGCTs were similar in terms of age, sex, estimated duration of disease, baseline cortisol and ACTH levels. SGCTs were larger than DGCTs (p=0.034). The remissions with surgery rates were similar between the groups; however, hypothalamic-pituitaryadrenal axis recovery time was longer in SGCTs (p=0.033). Persistent disease after surgery was slightly higher in DGCTs and recurrences were frequent in SGCTs; however, the differences were not statistically significant. Conclusion: DGCTs are often small microadenomas, while SGCTs are larger. Recurrences were slightly more common in SGCTs; however, further studies including larger series are needed to be able to obtain more significant results.

Proliferation Marker (Ki67) in Sub-Categorization of Neuroendocrine Tumours of the Lung

Rashi GARG, Amanjit BAL, Ashim DAS, Navneet SINGH, Harkant SINGH — 2019-01-01

Objective: The 2015 WHO classification classifies neuroendocrine tumours (NET) of the lung into typical carcinoid, atypical carcinoid, large cell neuroendocrine carcinoma and small cell carcinoma based on morphology alone. Mitosis is the major parameter for this classification, and thus several studies have focused on the role of Ki67 in these tumours but without conclusive results. The aim of the study was to categorize neuroendocrine tumours of the lung based on morphology and to assess the utility of Ki67 in diagnosis. Material and Method: The study included 42 cases (23 biopsies and 19 lobectomy specimens) of neuroendocrine tumours (excluding small cell carcinoma). Haematoxylin & eosin stained sections, immunohistochemistry for neuroendocrine markers and Ki67 were studied. Results: Based on WHO criteria, cases were classified as typical carcinoids (83.3%), atypical carcinoids (12%) and large cell neuroendocrine carcinomas (4.7%). The Ki67 index ranged between 1%-10% (mean 2.6%), 10%-30% (mean 19%), 35%-50% (mean 42.5%) in typical carcinoid, atypical carcinoid and large cell neuroendocrine carcinoma respectively. Using the ROC curve, the cut off value of Ki67 for typical and atypical carcinoids was 7.5% (P value<0.001), and for atypical carcinoid/large cell neuroendocrine carcinoma was 32.5% (P value=0.051). On comparing the size and infiltration pattern (both local and lymphovascular invasion) of tumours in resected specimens, there was no association with the proliferation index (P value >0.05). Conclusion: Morphological features are the gold standard for subtyping of neuroendocrine tumours. Ki-67 is a potentially meaningful marker for sub-categorization of lung NETs, especially in small biopsies. However, the size and infiltrative pattern of the tumours are independent of the proliferation index.

Diagnostic Value of Glucose Transporter 1 (GLUT-1) Expression in Nested Variant of Urothelial Carcinoma

Ceren BOYACI, Kemal BEHZATO�LU — 2019-01-01

Objective: Nested variant is bland-looking but aggressive subtype of urothelial carcinoma (UC). Cases having significant muscle invasion do not cause problems but small and superficial biopsies may be challenging due to morphological similarities between nested variant urothelial carcinoma and benign urothelial lesions. Material and Method: We studied Glucose transporter 1 (GLUT-1), which is an integral membrane protein providing glucose pass through plasma membrane down its concentration gradient, to see if it is useful for the differential diagnosis. Twenty five cases of nested variant urothelial carcinoma and a control group consisting of 12 cases of cystitis glandularis, cystitis cystica and 4 cases of inverted papilloma were stained with GLUT-1 immunohistochemically. Membranous staining was scored on a scale of 0 to +3. Results: Eleven of 25 nested variant UC cases showed a score of 2 and 14 of them showed a score of 3 on immunostaining with GLUT-1. Two cases showed a score of 1 and 10 cases did not show any staining in the control group. Conclusion: Our results showed that GLUT-1 may be a helpful marker when morphological separation cannot be made between nested variant UC and benign urothelial leisons. We also think that anti-GLUT-1 antibody treatment may be an option in the targeted treatment of nested variant.

Placenta, Secret Witness of Infant Morbidities: The Relationship Between Placental Histology and Outcome of the Premature Infant

2019-01-01

Objective: The microscopic and macroscopic features of the placenta can contribute to the clinical understanding of premature delivery. The aim of our study was to figure out the relationship between the histopathological findings of the placentas of premature deliveries and its effects on neonatal morbidity and mortality. Material and Method: The placentas of 284 singleton preterm infants with <35 weeks of gestation were examined. Three groups were created as the normal, chorioamnionitis and vasculopathy groups according to the histopathological findings in the placentas of the subjects. Results: The mean gestational age of the infants in the study group was 30.5 � 3.2 weeks, and the mean birth weight was 1588 � 581 g. The pathology was normal in ninety-six (33.8%), vasculopathy in 153 (53.9%) and chorioamnionitis in 35 (12.3%). The gestation age of the infants was lower in the chorioamnionitis group. Moreover, retinopathy of prematurity, early onset neonatal sepsis, and duration of respiratory support were found to be higher in the chorioamnionitis group. In the vasculopathy group, preeclampsia and small for gestational age were found to be significantly higher. Conclusion: Histopathological findings of the placentas from preterm deliveries provided important data in determining the etiology of preterm delivery and outcomes of infants. Infants delivered by mothers with chorioamnionitis were particularly found to be more preterm, and these preterm infants would have a longer hospital stay, higher respiratory support requirement, and more serious morbidities.

Detection of Anaplastic Lymphoma Kinase Gene Re-Arrangement in Non-Small Cell Lung Carcinoma in the Indian Population: Comparison of Techniques and Immunohistochemistry Clones

2019-01-01

Objective: Predictive and prognostic markers have revolutionized personalized therapy in non-small cell lung carcinoma (NSCLC). Crizotinib is now approved for locally advanced or metastatic NSCLC that is anaplastic lymphoma kinase (ALK) positive by either Fluorescence in situ hybridization (FISH) or immunohistochemistry (IHC). The current study aimed to detect the incidence of ALK gene re-arrangement in the Indian population, to compare the various IHC antibodies with FISH as a gold standard, and to analyze the morphology of cases with ALK phenotype. Material and Method: A case series of 614 cases of NSCLC were included. IHC for detection of ALK phenotype was compared with FISH using 5A4 clone (Labvision, USA), ALK-1(Dako, Denmark) and D5F3 clone (Ventana, USA). Results: ALK gene rearrangement was evident in 4.07% of the cases. Cases with ALK phenotype had unique histomorphology with presence of mucin or signet ring cells in association with necrosis, high tumour grade and poor differentiation. Comparison of various antibody clones used in IHC revealed that the sensitivity and specificity using the D5F3 clone (100%, 100%) and 5A4 clone (87.5%, 100%) were similar while the ALK-1 clone had the lowest sensitivity and specificity (50%, 95.5%). Conclusion: The incidence of ALK gene rearrangement in NSCLC in the current Indian study is within the worldwide reported range of 3-5%. This is the first study from the Indian subcontinent to compare various IHC antibodies used for detection of ALK phenotype. IHC using D5F3 clone and 5A4 clone may be considered as a rapid reliable and inexpensive method for detection of ALK gene rearrangement.

Frozen Section Evaluation in Head and Neck Oncosurgery: An Initial Experience in a Tertiary Cancer Center

2019-01-01

Objective: Frozen section evaluation is routinely used by oncosurgeons across specialties for rapid assessment of the presence of tumor in any tissue and its most common use is in surgical margins. Today, the use of intraoperative frozen-section evaluation of surgical margins is an accepted and frequent practice in head and neck oncology. This study aims to determine the efficacy and accuracy of frozen sections in head and neck cancer patients and compare the results with the respective paraffin sections and also to analyze the reasons for any disparity between them. Material and Method: A retrospective study was conducted to evaluate efficacy and accuracy of frozen section in head and neck cancer of 265 patients, treated at a tertiary cancer centre hospital between January 2013 to December 2014. Results: Out of 265 cases, it was found that 12.6% of these sections showed true positivity, 6.3% false positivity, 2.9% false negativity and 78.2% true negativity. The study also shows a sensitivity of 82.05% and specificity of 96.46%. Conclusion: Our study shows that intraoperative frozen section reports are specific and highly sensitive. We recommend a minimum of 3-4 sections, optimum cryostat temperature, good section thickness and quality staining for a good concordance rate.

Primary Clear Cell Renal Cell Carcinoma with Marked Intraluminal Mucin Secretion

O�uzhan OKCU, Kemal BEHZATO�LU, Yasemin �AKIR, Esra PA�AO�LU, U�ur Y�CETA� — 2019-01-01

Clear cell renal cell carcinoma with mucin secretion is an unexpected situation. Primary renal adenocarcinoma and various metastatic carcinomas should be considered in the differential diagnosis. Prognostic significance is not yet fully known due to the limited number of reported cases, and these lesions have been grouped under unclassified renal cell carcinoma. In our study, clear cell renal cell carcinoma with significant luminal mucin secretion is discussed with its histological, histochemical and immunohistochemical features.

Tricuspid Valve Hemangioma Associated with Hypoplastic Left Heart Syndrome Presenting as Sudden Infant Death Syndrome

Brijnandan GUPTA, Shouriyo GHOSH, Maikal KUJUR, Khushbu KHETAN, Tarun KUMAR — 2019-01-01

Primary cardiac tumors are rare in children with a low incidence varying from 0.0017 to 0.28% in autopsy studies. Approximately 90% of the reported primary cardiac tumors in the pediatric population are benign and the most common subtype is rhabdomyomas accounting for approximately 60%, while hemangiomas are rare primary tumors with a 5% incidence. Hypoplastic left heart syndrome is abnormal development of the left-sided cardiac structures, leading to obstruction of blood flow from the left ventricle out-flow tract. Here we report a case of tricuspid hemangioma in association with hypoplastic left heart syndrome, a rare association not previously reported in the literature.

Fascioliasis: A Rare Parasitic Infection-Mimicking Tumor in the Liver: Report of Two Cases

2019-01-01

Fascioliasis is a rarely encountered parasitic infection in Turkey that mainly affects the liver and bile ducts. Other defined localizations of the parasite are the lungs, gastrointestinal system, and subcutaneous fatty tissue. Two cases of female patients who presented to the hospital with abdominal pain and whose physical examination and laboratory findings were normal except peripheral eosinophilia, were detected to have liver masses with necrotic areas. Segmental hepatectomies were performed in both cases with the preliminary diagnosis of liver tumors. Upon microscopic examinations of the resection materials, necrotic granulomatous inflammation with eosinophilic reaction at the periphery and the parasite (Fasciola hepatica) were seen. Both cases were reported to be fascioliasis according to these findings. Two cases of fascioliasis mimicking malignancy in the liver are presented here together with literature findings.

Teratoid Wilms Tumor: Report of Three Cases and Review of the Literature

Doaa AL GHAMDI, Nasir BAKSHI, Mohammed AKHTAR — 2019-01-01

Teratoid Wilms tumor is a rare variant of Wilms tumor composed predominantly of well-differentiated epithelial and/or mesenchymal heterologous elements. Like the classical Wilms tumor, this variant may also occur as a renal mass or may be found in extra renal locations. This tumor may be treated effectively by surgical resection; however, it generally fails to respond to chemotherapy. A review of the literature revealed 30 reported cases of intra renal and 5 reports of extra renal teratoid Wilms tumor. We report our experience with an additional three cases of renal teratoid Wilms tumor adding to the 30 cases previously reported.

Primary Retroperitoneal Teratoma with Predominant Neurogenic Elements Masquerading as Adrenal Tumor

Sonam SHARMA , Leelavathi DAWSON, Ashish Kumar MANDAL — 2019-01-01

Primary retroperitoneal teratomas are uncommon extragonadal nonseminomatous germ cell tumors that are composed of well differentiated parenchymal tissues which are derived from more than one of the three embryonic germ cell layers. Here we report an unusual and first of its kind, a case of primary mature cystic retroperitoneal teratoma mimicking as adrenal tumor in a 7-month-old female in which the tumor was predominantly composed of neurogenic tissue histologically which is unlike the usual pattern seen in the teratomas.

Hodgkin Lymphoma in a Case of Chronic Myeloid Leukemia Treated with Tyrosine Kinase Inhibitors

2019-01-01

Chronic myeloid leukemia (CML) is characterized by increased and unregulated proliferation of granulocytic lineage in the bone marrow and presence of these immature myeloid cells in the peripheral blood with presence of Philadelphia (Ph) chromosome. Tyrosine kinase inhibitors are the most important drugs in the CML therapy and provide long disease-free survival. Due to the increased survival of CML patients with continual administration of these drugs, the chance of development of secondary malignancies may increase. The most common secondary malignancies are prostate, colorectal and lung cancer, non-Hodgkin lymphoma, malignant melanoma, non-melanoma skin tumors and breast cancer. Herein, we are describing a rare case of Hodgkin lymphoma in a patient of CML after ten year of primary disease presentation. Hodgkin lymphoma in a known case of CML is very rare and further studies are also needed to know the pathogenic relationship between the two entities and to assess the risk of secondary Hodgkin lymphoma in CML patients treated with tyrosine kinase inhibitors. CML itself is a risk factor for development of solid cancers and hematologic malignancies. In addition, patients on chemotherapy are immune-compromised and may be at greater risk of neoplasm driven by infectious agents such as Epstein-Barr virus.

Clear Cell Myoepithelial Carcinoma of the Upper Lip -A Rare Case Report

Swati GOTMARE, Anish GUPTA, Megha JAIN, Mandavi WAGHMARE — 2019-01-01

Myoepithelial carcinomas are quite infrequent neoplasms and coupled with their diverse morphological appearance are interesting as far as diagnosis and management is concerned. They account for less than 1% of all salivary gland tumors. The variable morphologic appearance of myoepithelial carcinoma leads to a wide differential diagnosis, including primary salivary gland tumors and metastatic tumors. The prognosis of these tumors is not fair as they are locally aggressive and approximately one third of the patients die of the pathology. We report a case of clear cell variant of myoepithelial carcinoma in an unusual location, i.e. the upper lip. The treatment carried out was wide surgical resection. The patient was followed up for 2 years and was symptom free. The clear cell variant of myoepithelial carcinoma is extremely rare and only about 51 cases of this variant affecting the salivary glands have been reported worldwide so far.