Turkish Journal of Pathology - 2021; 37(1)

Thyroid Cancer After Chernobyl: Re-Evaluation Needed

Sergei JARGIN — 2021-01-01

Thyroid carcinoma in people exposed to radiation during their childhood and adolescence is the only solid cancer for which the incidence increase as a result of the Chernobyl accident is regarded to be proven. The main evidence in favor of a cause-effect relationship between radiation and thyroid cancer incidence increase comes from epidemiologic studies. Bias in some studies was caused by the screening effect, improved diagnostics after the accident, overdiagnosis, registration of patients from non-contaminated territories as Chernobyl victims, recall bias, dose-dependent selection and self-selection. Prior to the accident, the registered incidence of pediatric thyroid carcinoma was lower in the former Soviet Union than in other industrialized countries i.e. there were undiagnosed cases in the population. The screening found not only small nodules but also late-stage tumors interpreted as radiogenic cancers developing after a short latency. Pediatric thyroid cancers detected during first 10 years after the accident were larger than those detected later on average, many tumors being poorly differentiated and metastatic. The relationship of thyroid cancer and Chernobyl exposures is not denied here; however, it is argued that the quantity of radiogenic cases has been overestimated according to the mechanisms discussed in this paper. In addition, it is suggested that results of some Chernobyl-related molecular-genetic and other studies should be re-evaluated, considering that many tumors detected by the screening or brought from non-contaminated areas and registered as exposed to the fallout were advanced cancers.

Clinicopathological and Prognostic Significance of the EML4-ALK Translocation and IGFR1, TTF1, Napsin A Expression in Patients with Lung Adenocarcinoma

P�nar BULUTAY, Nalan AKY�REK, Leyla MEMI� — 2021-01-01

Objective: Patients with lung adenocarcinoma who harbor ALK gene rearrangements can demonstrate significant clinical benefit with ALK tyrosine kinase inhibitors. Insulin-like growth factor receptor 1 (IGFR1) is a cellular membrane receptor that is overexpressed in many tumors. It plays an important role in cancer progression and is associated with increased postoperative recurrence and poorer disease-free survival. The aim of this study was to determine the EML4-ALK mutation and IGFR1 expression in lung adenocarcinoma and analyze their prognostic value. Material and Method: In this study, we analyzed the EML4-ALK mutation using the FISH and IHC techniques in 251 lung adenocarcinoma (203 primary resections, 48 metastasectomies) cases. Correlative analyses were performed between the EML4-ALK mutation, the IGFR1, TTF1, and NapsinA expression, and the clinicopathologic factors in lung adenocarcinomas. Results: The EML4-ALK mutation was observed in 3.8% of the cases and it was associated with the solid pattern, signet ring cell morphology, and larger tumor size. IGFR1 expression was identified in 49% of the cases and most of the ALK-mutated cases were also expressing the IGFR1 protein (66%). IGFR1 expression frequency was increased in metastasectomy specimens. Conclusion: A solid signet-ring cell pattern or mucinous cribriform pattern was present at least focally in all ALK-positive tumors, consistently with the literature. In addition, IGFR1 expression levels showed an increase in the EML4-ALK-mutated cases in our series, but the clinical significance of this finding should be supported by larger series and survival analysis. Our findings show that IGFR1 expression may be useful as a poor prognostic marker in patients with lung adenocarcinoma.

L�wenstein-Buschke: Clinicopathologic Analysis of 78 Cases of Large and Giant Condyloma Acuminata of the Anus

2021-01-01

Objective: The nature and clinicopathologic associations of L�wenstein-Buschke disease are unclear. Materials and Methods: 78 anal condylomatous lesions (≥2 cm) were analyzed. Cases were classified based on size as �medium-large�(2-5 cm, n=59), �large� (5-10 cm, n=13) and �giant� (>10 cm, n=6). Results: Patients were predominantly males (male/female=70/8). The mean age was 38 years (range:20-66). Two distinct lining types were recognized: 1) Epidermal type, typically lacking overt koilocytotic change, with associated invasive carcinoma in 8%; 2) Mucosal type, often manifesting koilocytotic change, with associated invasive carcinoma in 21%. Three types of high-grade dysplasia were discerned: 1) Basaloid, 8/9 showing high-grade dysplasia/carcinoma in-situ but non-invasive lesions; 2) Keratinizing, innocuous-appearing, but 5/6 was associated with invasion; 3) Giant cell, showing scattered individual bizarre cells, with 3/5 showing invasive carcinoma. Overall, invasion was found in 14% of the cases. The bulbous, broad-based destructive pattern characterizing verrucous carcinomas of the upper aerodigestive tract was not observed. A statistically significant trend existed between the incidence of invasion and size: 8.5% for medium-large, 23% for large, and 50% for giant (p=0.02). There was no discernable trend in the depth of invasion relative to condyloma size. Conclusions: Our findings suggest that L�wenstein-Buschke lesions are mega versions of conventional condyloma. Being verrucoid, large and minimally invasive, they can be conceptually regarded as a form of verrucous carcinoma, but they do not display the histologic characteristics of verrucous carcinoma defined in the aerodigestive tract. They exhibit two types of linings: the mucosal type that often shows koilocytotic changes, and the epidermal type that can be difficult to recognize in biopsies. These lesions may be associated with invasive carcinoma, albeit limited in amount.

Stromal Lymphoid Response Status in Micropapillary Urothelial Carcinomas Diagnosed in Bladder Transurethral Resections and its Comparison with Conventional Urothelial Carcinomas

Ezgi HACIHASANO�LU, U�ur Y�CETA�, O�uzhan OK�U, Kemal BEHZATO�LU — 2021-01-01

Objective: Micropapillary urothelial carcinoma is an aggressive variant of urothelial carcinoma. Evidence suggests that the relationship between the tumor and inflammatory cells is important in tumor progression and the treatment response. We evaluated the stromal lymphoid response in micropapillary urothelial carcinomas and compared it with conventional urothelial carcinomas. Material and Method: Among bladder transurethral resection materials diagnosed as �invasive urothelial carcinoma� between January 2010-March 2017, cases with at least 5% micropapillary urothelial carcinoma were evaluated for age, gender, grade, stage, micropapillary urothelial carcinoma percentage, presence/percentage of accompanying conventional urothelial carcinoma/urothelial carcinoma variants, in situ urothelial carcinoma/micropapillary urothelial carcinoma, lymphovascular invasion, necrosis, and stromal lymphoid response. Stromal lymphoid response was scored as 0-1-2-3. All parameters were evaluated in 50 pure conventional urothelial carcinomas. Results: Among 47 micropapillary urothelial carcinomas, 41 were male. The mean age was 69 years. pT1/pT2 was 23/24. Six cases were pure MPUC. Lymphovascular invasion was present in 8, necrosis in 9 cases. Stromal lymphoid response was present and scored as 1-2-3 in 32 micropapillary urothelial carcinomas (68.1%) and 48 conventional urothelial carcinomas (96%). Micropapillary urothelial carcinomas had significantly higher lymphovascular invasion and pT2 rates and lower stromal lymphoid response. Conclusion: Low stromal lymphoid response in micropapillary urothelial carcinomas can be responsible for the poor clinical outcome and impaired response to treatment of these tumors. This is the first study in the English literature to demonstrate a lower stromal lymphoid response rate in micropapillary urothelial carcinomas compared to conventional urothelial carcinomas.

Evaluation of the Performance of CinTec� PLUS in SurePathTM Liquid-Based Cervico-Vaginal Samples

Pooja SHARMA, Parikshaa GUPTA, Nalini GUPTA, Vanita SURI, Arvind RAJWANSHI — 2021-01-01

Objective: Cervical cytology and Human papillomavirus (HPV) testing are effective screening techniques but both have limitations. A few recent studies in the literature have highlighted the role of co-expression of p16INK4a and Ki-67 for cervical cancer screening. The present study was undertaken to evaluate the diagnostic performance of the CINtec� PLUS kit (dual immunostaining for p16 and Ki-67) in SurePathTM liquid-based (LBC) cervico-vaginal samples. Materials and Methods: This was a prospective study performed on 52 cervico-vaginal SurePath� LBC samples reported as having squamous epithelial cell abnormality (ECA). All the samples were stained using CINtec� PLUS kits. Additionally, HPV-DNA testing was also done and the results were compared. Results: The age range was 34-74 years. ECA included 18 (34.6%) cases of ASC-US, 9 (17.3%) cases of low-grade squamous intraepithelial lesion (LSIL), 11 (21.2%) cases of high-grade squamous intraepithelial lesion (HSIL), and 14 (26.9%) cases of squamous cell carcinoma (SCC). Cervical biopsies were available in 19 (36.5%) cases. A total of 34/52 (65.4%) cases were positive for HPV-DNA (5/18-ASC-US; 6/9-LSIL; 10/11-HSIL; 13/14-SCC). The CINtec� PLUS test was positive in 41/52 (78.8%) cases (11/18-ASC-US; 6/9-LSIL; 11/11-HSIL; 13/14-SCC). On comparing CINtec� PLUS positivity (78.8%) with HPV positivity (65.4%), dual positivity was seen in 3/18 cases of ASC-US, 6/9 cases of LSIL, 10/11 cases of HSIL, and 12/14 cases of SCC. One case each of HSIL and SCC was negative on the HPV test and was positive on CINtec� PLUS. Conclusions: CINtec� PLUS test helps to improve the detection of pre-cancerous cervical lesions as compared to cervical cytology or HPV testing alone and hence can serve as a potentially useful diagnostic and triage tool, especially for indeterminate cases.

How Does It Feel to Be a Pathologist in Turkey? Results of a Survey on Job Satisfaction and Perception of Pathology

Burcin PEHLIVANOGLU, Hur HASSOY, Gulen GUL, Umut AYKUTLU, Basak DOGANAVSARGIL — 2021-01-01

Objective: Job satisfaction affects productivity and professional performance in many aspects; however, there is limited data regarding pathologists� job satisfaction. Hence, in this study, we aimed to evaluate surgical pathologists� job satisfaction in Turkey. Materials and Methods: We conducted a 59-item web-based survey questioning respondents� institutional background, history of training, continuing education status/research activities, physical conditions, professional well-being, and job satisfaction level. Likert-type and open/ close ended questions were asked and scored. The participants were also asked to complete the Minnesota Satisfaction Questionnaire-Short Form. Results: Of the 321 respondents, 75% were female, the median age was 41 years (range 28-71 years), experience as a pathologist ranged between 0.12 and 44 years (mean 11.4�9.16 years). Academic pathologists, senior pathologists with ≥20 years of experience, and pathologists working at large institutions and living in developed cities expressed better physical conditions, higher satisfaction with working conditions and, therefore, higher overall job satisfaction (p<0.05). 98% agreed that pathologists have a critical impact on patient management; however, the majority (>80%) thought that patients barely know what pathologists do and other physicians rarely understand the difficulty and limitations in pathology practice. 82% were happy to have chosen pathology but 45% reported to experience the feeling of being �burnt out�. Conclusions: Our findings suggest that younger pathologists are less satisfied with their jobs and a surgical pathologist�s job satisfaction increases with the physical and technical quality of the pathology laboratory/institution, and years of experience. Pathologists seem to be aware of their important role in patient management although they think that pathology remains �invisible� to many physicians and patients.

Ground Glass-Like Inclusions: Associated with Liver Toxicity

Kemal DENIZ — 2021-01-01

Objective: The etiology of ground glass-like inclusions is heterogenous and the pathology has been described in various conditions including HBV infection, Lafora�s disease, fibrinogen storage disease, type IV glycogenosis, and alcohol reversion therapy. Similar ground glass-like inclusions are also associated with immunosuppressed conditions and multiple medications, for which the clinical significance is still unclear. Additional cases, some with previously unreported unique etiologies, and their follow-up were described in this study. Materials and Methods: Eleven cases were examined between 2008 and 2019 for this study. The clinical data and histologic slides were reviewed. All of the cases were negative for Hepatitis B virus. None of the patients declared alcohol intake or a history of epilepsy. Results: Liver histology showed mild lobular inflammation in most of the cases (72%). Ground glass-like hepatocytes were distributed in the patchy-panlobular, periportal, and centrizonal pattern at 55%, 27%, and 18%, respectively. Clinical history revealed medication use in nine (82%) patients including NSAIDs, steroids, and chemotherapy. Ground glass-like inclusions were related to herbal toxicity in two of the patients. Liver function tests were elevated in all of the cases. Follow-up data revealed four patients with malignancy who died of their cancer. Seven patients showed resolution of elevated liver enzymes with a median follow-up period of 37 months (range 7-132 months). Conclusions: Medication is the most relevant etiology for the development of these inclusions. Ground glass-like inclusions may also seen in herbal toxicity. Transplantation was not an etiologic factor in our patients. Most of the patients displayed an indolent course with resolution of the elevated transaminases.

Interobserver Agreement in Histopathological Subtyping of Malignant Pleural Mesotheliomas

Mona MLIKA, Faouzi MEZNI — 2021-01-01

Objective: Many recent studies are pointing out the heterogeneity between pathologists in the classification of malignant pleural mesotheliomas. Besides, they reported the prognostic impact of classifying epithelioid mesotheliomas according to the predominant architectural features and the nuclear grade. The authors assessed the interobserver and the intraobserver agreement of subtyping mesotheliomas between 2 pathologists used to thoracic pathology. Material and Method: The observers reviewed all the slides of the malignant pleural mesotheliomas diagnosed during the period ranging from 2004 to 2017. The Cohen Kappa was performed in order to evaluate the agreement between both observers into classifying mesotheliomas, subtyping and grading epithelioid mesotheliomas. Two rounds of examination were planned with a delay period of one month. After the first round, the reviewers discussed the different difficulties and challenges they faced. All the statistic tests were performed using the SPSS software version 12.0. Results: After the first round, a fair agreement between both observers was reported. After the second round, an improvement of the concordance rate with a good agreement in subtyping epithelioid mesotheliomas was noticed. Concerning the grading of mesotheliomas, the interobserver agreement was poor even after the second round examination. The intraobserver reproducibility of epithelioid mesothelioma subtyping was fair or moderate for both reviewers. The intraobserver agreement was poor concerning the grading of epithelioid mesothelioma. Conclusion: Integrating subtyping and grading of epithelioid mesotheliomas into a new classification necessitates an important training of the pathologists. The architectural features� definitions have to be clarified in order to avoid using own subjective opinions and habits by pathologists.

IgG4-Related Disease of the Ovary

Sevda AKYOL, Fatma �Z ATALAY, Secil HASDEMIR, �mer YERCI — 2021-01-01

Immunoglobulin G4-related disease is characterized by dense fibrosis, obliterative phlebitis, and lymphoplasmacytic infiltration that contains abundant IgG4 positive plasma cells. It causes tumefactive lesions in the involved organs and is most commonly seen in the salivary glands, pancreas, and retroperitoneum. Ovarian involvement has been reported in only two cases. In our case, a 58-year-old female patient presented with abdominal distention and pain. Pelvic computed tomography revealed a soft tissue lesion compatible with the omental cake, several intraabdominal implants, and bilateral adnexal fullness. A laparotomy was performed under suspicion of peritoneal carcinomatosis secondary to bilateral adnexal mass. In the histopathologic examination, abundant lymphoplasmacytic infiltration and dense fibrosis were observed in both ovaries and the peritoneum. In the areas of greatest density, the density of IgG4-positive plasma cells was found to range from 40 to 50 per high-power field. The patient was accepted as suffering from probable IgG4-related disease because of the bilateral involvement of the ovaries and the histopathological findings. In conclusion, we present this case to draw attention to the fact that IgG4-related disease can also be seen in the ovary.

Primary Cutaneous Myxoid Spindle Cell Squamous Cell Carcinoma of the Scalp: A Case Report

Recep BED�R, Mehpare SUNTUR, Orhan SEMERC� — 2021-01-01

Cutaneous squamous cell carcinomas are the second most frequent type of non-melanoma skin cancer. A 78-year-old man with a slow-growing but large nodular lesion on his scalp presented to the hospital. The nodular lesion was excised. Histologically, the lesion was diagnosed as a primary cutaneous myxoid spindle cell squamous cell carcinoma, which is the subject of this case report. Extracellular mucin production is an even less common finding in SCC. We also aim to discuss the histological and immunohistochemical findings for distinguishing MSC SCC from other primary cutaneous and metastatic spindle cell neoplasms with myxoid stroma.

ALK1 Gene Rearranged Pulmonary Sarcomatoid Carcinoma Masquerading as Tuberculosis in a Young Male

Ayushi SAHAY, Rajiv KUMAR, Amit JANU, Kumar PRABHASH — 2021-01-01

Pulmonary sarcomatoid carcinoma is rare, with limited treatment options and poor prognosis. In contrast to other non small cell lung carcinomas, not much is known about its molecular biology. In an endemic country like India, lung cancer is often masked by tuberculosis and presents in advanced stages. We report here an unusual case of pulmonary sarcomatoid carcinoma, in a young non-smoker male, who had co-existent tuberculosis masking and delaying the diagnosis of malignancy. On molecular study, the tumor showed ALK gene rearrangement, both by immunohistochemistry and fluorescence in-situ hybridization, which has been reported only twice previously. Presence of ALK gene rearrangements in sarcomatoid carcinoma has significant therapeutic implications and potential for altering the prognosis of this fatal disease. Hence we recommend performing ALK gene rearrangement analysis in all cases of sarcomatoid lung carcinomas. The report discusses the diagnostic approach and provides insight into the molecular pathogenesis of this exceedingly rare malignancy.

IgG4-Related Disease with Selective Testicular Involvement- A Rare Entity: Case Report with Review of Literature

2021-01-01

Immunoglobin-G4 related disease (IgG4-RD) is an auto-immune inflammatory condition where patients present with a tumour-like mass that shows infiltration by plasma cell and subsequent fibrosis. It is a systemic condition that primarily involves the salivary glands, pancreas, kidneys, aorta, and retroperitoneum amongst other organs. Testicular involvement is a rare occurrence in this disease entity. A 55-year old male patient presented with the complaints of pain and swelling in the right scrotal region. Right-sided orchidectomy was carried out which on histopathology showed features suggestive of IgG4-RD which was later confirmed on immunohistochemistry. Whole body MRI revealed that no other organ was involved in the disease process in this patient. IgG4-RD has a variable clinical course and considerable overlap with its differentials. Imaging studies and serum IgG4 levels are neither confirmatory nor customarily diagnostic in every case. The only confirmatory diagnostic investigation is histopathological examination, which shows infiltration of IgG4+ plasma cells and fibrosis in the involved tissue. Whenever a mass-forming lesion with typical histomorphological features is encountered with involvement of multiple organs/anatomic sites, IgG4-related disease should be considered among the differentials, and clinicians of all disciplines should be familiar with this disease entity.

Metastatic Epithelial-Myoepithelial Carcinoma in a Female Presenting with Neck Mass and Lytic Lesion in Acetabulum: A Diagnostic Challenge on Cytology

Parikshaa GUPTA, Arvind RAJWANSHI, Nandita KAKKAR — 2021-01-01

Epithelial-myoepithelial carcinoma (EMC) is a rare, low-grade, malignant salivary neoplasm. Establishing an accurate cytological diagnosis is often challenging owing to its rarity, bland cytologic appearance and variable representation of cell populations in the smears. The diagnostic struggle is more so when the aspiration is from a metastatic site with an unknown primary, as in such cases the list of differential diagnoses expands further. A 58-year-old female presented with a low-back pain from last one month. On examination, she also had a level III, right cervical swelling for the last 20 years. Radiology revealed a lytic lesion in the left acetabulum. She had undergone surgery 35 years ago for a right-sided upper neck swelling, the medical records of which were not available. Fine needle aspiration (FNA) from the cervical swelling was performed. The smears were cellular and showed predominantly dispersed, round to polygonal tumor cells with mild pleomorphism, eccentric nuclei, coarse chromatin, occasional nucleoli and moderate cytoplasm with some showing vacuolations. The cell-block section revealed tumor cells arranged in the form of tubules lined by dual layer of tumor cells without any chondromyxoid stroma. On immunocytochemistry, the luminal cells showed positivity for CK7 (epithelial marker) and the abluminal cells showed positivity for p63 (myoepithelial marker). Based on these features, a final diagnosis of metastatic epithelial-myoepithelial carcinoma was rendered. The present report highlights the characteristic cytomorphological and immunocytochemical features of EMC and reiterates the diagnostic accuracy of FNAC for diagnosis of such challenging cases.

Pulmonary Acantholytic Squamous Cell Carcinoma Mimicking Lepidic Pattern Adenocarcinoma

Rukiye YILMAZ, Recep BED�R — 2021-01-01