What�s in a Name? Michael N. Marsh, BTh, DPhil, DM, DSc, FRCP

Arzu ENSAR� — 2021-09-01

The Role of Immunocytochemical Markers to Differentiate Primary from Secondary Neoplastic Hepatic Masses: A Diagnostic Challenge on Cytology

Jenna B BHATTACHARYA, Shyam Lata JAIN, Subbarayan DEVI — 2021-09-01

Objective: It is challenging and difficult to differentiate primary from metastatic hepatic masses solely on cytology. The present study aimed to correlate cytomorphological spectrum of hepatic masses with immunocytochemical markers to differentiate primary from metastases in liver. Material and Method: The present study comprised of 30 clinico-radiologically suspicious cases of neoplastic hepatic masses. Ultrasound-guided fine needle aspiration smears and cell blocks were prepared as per standard technique; two of the smears were air-dried and Giemsa stained to study cytomorphological features. A panel of markers (HepPar-1, CD 10, CK7, CK19, CD34, and MOC-31) were studied both in smears and cell blocks. Results: Cytomorphological features on smears were evaluated and correlated with immunocytochemistry in all cases; the final diagnosis was: Hepatocellular carcinoma (n=7), cholangiocarcinoma (n=2), hepatoblastoma (n=1) and metastatic carcinoma (n=20). HepPar-1, CD10 and CD34 demonstrated 86%, 72%, 86% sensitivity and 100% specificity respectively for hepatocellular carcinoma; CK7&CK19 showed 100% sensitivity for cholangiocarcinoma, MOC 31 showed 90% sensitivity and 100% specificity for metastatic carcinoma.

Metastases to the Stomach: Clinicopathologic Features of Metastases Mimicking Gastric Primaries

2021-09-01

Objective: Metastatic involvement of the stomach is a rare event. Our aim in this study was to document the clinicopathological findings in patients with gastric metastases and find out if there are any potentially significant features to be used in the differential diagnosis. Material and Method: Our cohort consisted of 17 histologically verified gastric metastasis cases. Clinical, endoscopic and microscopic features were retrospectively analyzed. Results: The primary sites were the breast, skin, lungs, ovaries, colon, and gluteal soft tissue. Three patients were symptomatic because of the metastatic involvement of the stomach and 9 patients had concomitant metastasis in other sites. Invasive lobular breast carcinoma and malignant melanoma were the most common metastatic malignancies. The most common macroscopic appearance was the diffuse infiltrative type (Borrmann Type 4). Most of the metastatic lesions endoscopically mimicked primary gastric cancer. Furthermore, some of the metastatic lesions, particularly invasive lobular carcinoma of the breast and malignant melanoma, displayed histopathologic features similar to the primary gastric malignancies to a certain extent. Conclusion: The possibility of metastatic involvement of stomach must be kept in mind while dealing with a gastric mass lesion in a cancer patient, even though the clinical and endoscopic features suggest primary gastric cancer. Our study points out the importance of conveying the information about medical history and clinical findings of the patients for correct pathologic differential diagnosis.

Cholemic Nephrosis: An Autopsy Study of a Forgotten Entity

2021-09-01

Objective: The aim of the study is to do a clinicopathologic study of post mortem kidney biopsies with significant deposition of bilirubin pigment within tubular epithelial cells and in the lumen of distal tubules as a bile cast. Material and Method: All post mortem specimens with acute tubular necrosis, with the presence of bile casts in tubules or bile pigment deposition in the tubular epithelium during the period 2015-2018 were examined for gross and histopathology along with biochemical parameters and viral markers. Results: Bile casts with sloughed renal tubular epithelial cells and occasional macrophages were present in the distal convoluted tubule in 78.6% of biopsies (11/14). The plugging of distal convoluted tubule with casts was similar to that seen in myeloma and myoglobin cast nephropathies. Bilirubin pigment deposition was present in 35.7% (5/14) of cases. The frequency of bile casts in each biopsy was variable and it did not have any association with serum bilirubin levels or etiology of liver dysfunction. A striking difference from earlier studies is the high number of toxin-induced liver damage including six cases of paraquat and 2 cases of yellow phosphorus poisoning. Conclusion: This study proves importance of the bile cast nephropathy as a reason for kidney injury, especially with varied hepatotoxic etiologies, especially paraquat and yellow phosphorus.

Peripheral Lymphadenopathy in Children: Cytomorphological Spectrum and Interesting Diagnoses

2021-09-01

Objective: Peripheral lymphadenopathy is a common complaint in the pediatric outpatient department. Fine needle aspiration cytology is the first investigation of choice with a high sensitivity for diagnosis but cytology may be challenging in some cases. The study was planned to study the cytomorphological spectrum and discuss a few interesting cases. Material and Method: 1890 paediatric subjects� up to 12 years of age with significant peripheral lymph node enlargement and an adequate cytology specimen were included in the study. Inadequate aspirates were excluded. Results: The majority of children presented within 4-8 years of age with a male to female ratio of 1.7:1. The anterior cervical group was most commonly affected, followed by the posterior cervical, axillary and inguinal. Reactive lymphadenitis constituted the majority of the diagnoses, followed by Tuberculosis, acute suppurative, BCG-induced lymphadenitis, Kimura disease, Rosai-Dorfmann disease and Kikuchi-Fujimoto disease. Lymphomas and metastatic malignancies were less common, and mainly consisted of Hodgkin lymphoma, non-Hodgkin lymphoma, anaplastic large cell lymphoma, and Langerhans cell histiocytosis. Cytomorphological features of a few challenging and interesting cases have been discussed. Conclusion: Non neoplastic causes of lymphadenopathy predominate in the pediatric age group. A definitive diagnosis rests upon a complete clinical, radiological, microbiological, and cyto-histopathological correlation with the use of ancillary techniques wherever necessary.

What Would Next Generation Sequencing Bring to the Diagnosis and Treatment of Sarcomas? A Series of 20 Cases, a Single Institution�s Experience

�brahim KULA�, P�nar BULUTAY, �isel AYDIN MER��Z — 2021-09-01

Objective: Soft tissue tumors comprise a small proportion of a pathologist�s routine practice. Although morphology and immunohistochemistry are quite helpful for diagnosing these tumors, many require molecular tests. Fluorescence in-situ hybridization has been the most commonly used method for the detection of specific genomic alteration, but next generation sequencing (NGS) could be more informative in many ways. Here we present our targeted NGS experience on soft tissue tumors with a series of 20 cases. Material and Method: The Laboratory Information System (LIS) was screened for soft tissue tumors that had been sequenced by NGS (between January 2018 - February 2021). 20 consecutive cases were included in the study. All cases were sequenced using a commercial targeted sequencing panel designed for soft tissue tumors. Results: We were able to run a reliable sequencing study for 16 (80%) of the cases but 4 (20%) of them failed in quality tests. We have found pathogenic alterations in 12 (60%) of the cases. The most common alterations were EWSR1 fusions, FLI1 being the most common partner. NGS results drastically changed the initial diagnosis, and thus the treatment modalities, in 3 cases (15%): the case with ETV6-NTRK3 fusion, the case with FUS-TFCP2 fusion, and the case of rhabdomyosarcoma (RMS) that was favored to be of the alveolar subtype and turned out to lack FOXO1 fusions. Conclusion: A targeted NGS panel is robust and very informative. It not only allows pathologists to further specify and/or confirm their diagnosis but it could also play an important role in predicting the outcome.

Does the Distance of the Tumor from the Surgical Margin Affect Biochemical Recurrence in Patients with Pathological Organ-Confined Prostate Cancer?

Ayse OZBEK, R�dvan OZBEK, Mehmet DUVARCI, Olcay KANDEMIR — 2021-09-01

Objective: To investigate the effect of the distance between tumor and surgical margin on biochemical recurrence in patients with organ-confined prostate cancer. Material and Method: The data of 208 patients, who underwent radical prostatectomy between 2012-2018, were retrospectively analyzed. The surgical margin status of 147 pathologically organ-confined patients was categorized as positive, close (<1mm) and negative. Surgical margin status and parameters affecting biochemical recurrence were examined. Furthermore, multivariate analysis was done to determine the parameters associated with biochemical recurrence. Results: Biochemical recurrence was detected in 21 (14.2%) of 147 patients. 38 (27.9%) men had negative surgical margins, 68 (46.2%) had close surgical margins and 41 (25.9%) had positive surgical margins. Tumor volume and ISUP grade were found to be statistically significant for positive surgical margin and close surgical margin patients compared to negative surgical margin patients. Close surgical margin was not statistically associated with biochemical recurrence. Preoperative high PSA (p<0.001) and positive surgical margin (p=0.021) were independent risk factors for biochemical recurrence. Conclusion: According to our results, it is not necessary to include the presence of a close surgical margin in the pathology reports in patients with pathological organ-confined tumors and negative surgical margins.

Prognostic and Predictive Significance of PD-L1 Expression in Non-Small Cell Lung Cancer Patients: A Single-Center Experience

Hac� ARAK, Ayd�n AYTEKIN, Ozlem CANOZ, Metin OZKAN — 2021-09-01

Objective: To investigate the prognostic and predictive value of PD-L1 expression in operated non-small cell lung cancer (NSCLC) patients and to analyze its relationship with clinicopathological factors. Material and Method: A total of 90 patients with operable NSCLC were included in this retrospective single center study. Tumor blocks of patients were stained immunohistochemically with PD-L1 polyclonal antibody. When evaluated immunohistochemically and statistically, patients with tumor staining percentage of ≥5%, those with +2 and +3 membranous staining intensity, and those with ≥50% H-Score were considered positive. The relationship between PD-L1 expression status and clinicopathological features in addition to the prognostic effect of PD-L1 on survival were statistically analyzed. Results: The frequency of PD-L1 expression was 37%, 15% and 5% according to the staining percentage, staining intensity, and the H-Score, respectively. There was no significant relationship between PD-L1 expression and age, gender, smoking, tumor stage and histological subtype (p> 0.05). However, PD-L1 expression was relatively higher in patients <65 years of age, men, smokers, patients with advanced tumor stage, and squamous cell subtype. Based on the analysis of the H-Score, no significant difference was noted regarding disease-free survival time between PD-L1 positive and PD-L1 negative patients (median 20 [95% CI 1.2-38.7] months vs. median 27 [95% CI 17.5-36] months, p=0.208). However, overall survival time was significantly shorter in PD-L1 positive compared to PD-L1 negative patients (median 24 months [95% CI 9.9-38] vs. median 48 months [95% CI 33.6-62.3], p=0.049). Conclusion: In patients with high PD-L1 expression, the biological behavior of the cancer was more aggressive, and the life expectancy was shorter. PD-L1 expression seems to be a poor prognostic marker in NSCLC patients.

Primary Myeloid Sarcoma of Ovary: A Case Report and Review of the Literature

Sevda AKYOL, Fatma OZ ATALAY — 2021-09-01

Myeloid sarcoma (granulocytic sarcoma or chloroma) is a tumor formed by myeloid precursor cells in any localization other than the bone marrow. It can occur without underlying acute myeloid leukemia (AML) or other myeloid neoplasms. Herein, we present a forty-two-year-old female patient who underwent surgery because of a left adnexal mass. Microscopic examination of the specimen revealed cord-like arrangement of the tumor cells with a diffuse growth of small blue cells effacing the ovarian stroma. Adult granulosa cell tumor was in the differential given the scanty cytoplasm of the tumor and in fact was the diagnosis of the referring institution. Further microscopic evaluation with immunohistochemical analysis at our institution revised the diagnosis to myeloid sarcoma. Myeloid sarcoma is a difficult tumor to diagnose due to its rarity, especially in the absence of a history of leukemia, and correct tissue diagnosis is essential for its treatment.

Cysts that Still Persist: A Case Series of Cysticercosis on Histopathological Evaluation

Flora D LOBO, Kudurugundi Basavaraju VATSALA, Deepa Adiga A S, Sharada RAI — 2021-09-01

Cysticercus is the infective larval form of the cystode T. solium that causes cysticercosis. It is has been declared as one of the neglected endemic zoonoses by the WHO. Poor sanitation, and consumption of undercooked infected pork and raw vegetables contaminated by human feces are the potential sources. Cysticercosis can affect various organs. India is one of the endemic countries where the parasite is prevalent in many states. This study aimed to analyze and report cases of cysticercosis based on the histopathological diagnosis. This is a retrospective study that included cases which had been reported as cysticercosis on histopathology from 2010 to 2018 at a tertiary care hospital. The clinical presentation of these cases along with macroscopic and microscopic features were reviewed. There were six cases of cysticercosis that were diagnosed on histopathology during the study period. Among them, two cases were intramuscular lesions, three were subcutaneous, and one case was an intraventricular lesion in the brain. Three of the cases presented as cystic lesions. On histopathological evaluation, cysts were identified in four cases on macroscopy. Microscopically, the cross section of the cysticercus was seen in all six cases with associated inflammatory change. To conclude, cysticercosis can clinically present as a benign neoplastic or an inflammatory lesion. Microscopic findings dictate the diagnosis of cysticercosis, although histopathological evaluation is not common.

Giant IgG4-Related Pseudotumor of the Esophagus Resected with Endoscopic Submucosal Dissection: A Case Report and Review of the Literature

Nese EKINCI, Duygu UNAL KOCABEY, Eylul GUN, Fatih ASLAN — 2021-09-01

IgG4-related disease (IgG4-RD) is a systemic autoimmune disorder that has been defined in various organs. The disease is characterized by typical clinicopathological features including a dense lymphoplasmacytic infiltrate rich in IgG4 positive plasma cells, storiform fibrosis, obliterative phlebitis, and often an elevated serum IgG4 level. Esophageal IgG4-RD is rare, and its presentation as a solid mass is even more rare. Only 15 previous cases of IgG4-related esophageal disease have been described. We herein present a case of giant IgG4-related pseudotumor of the esophagus resected with endoscopic submucosal dissection (ESD) and a review of the literature. The patient was a 67-year-old man who was admitted to our hospital for assessment of progressive dysphagia. Upper gastrointestinal endoscopy revealed a 9 cm mass in the cervical esophagus. In the previous two hospitals, the patient�s mass could not be diagnosed despite repeated biopsies. Because of concerns regarding malignancy, endoscopic submucosal dissection was performed. Histopathological examination showed dense lymphoplasmacytic infiltration with predominant IgG4-positive plasma cells on a sclerotic background. The patient was diagnosed with IgG4-RD. During the follow-up, no residual mass was detected but the patient was diagnosed with lung adenocarcinoma. We present a unique case of giant IgG4-related pseudotumor of the esophagus. Resection with ESD of such a big mass of IgG4-RD in the esophageal region has never been reported before in the literature.

A Case of Lafora Disease Diagnosed by Axillary Skin Biopsy

Elife KIMILO�LU, Pelin AKBA�, �zg�l ESEN �RE, �a�la TURAN — 2021-09-01

Lafora disease is a severe form of progressive myoclonic epilepsy with autosomal recessive inheritance diagnosed by inclusion body in biopsy. A 26-year-old woman was admitted due to complaints of frequent twitches and fainting. The 0.5x0.3x0.3 cm axillary skin punch biopsy was subjected to routine histopathological evaluation. Cytoplasmic PAS-positive inclusion bodies were observed at the basal side of the eccrine and apocrine glands. The diagnosis of Lafora disease can also be made by the observation of the polyglycosan cytoplasmic inclusion bodies in the brain, liver and skeletal muscle biopsies. Although we need more work to understand the etiopathogenesis of Lafora disease, we would like to draw attention to the importance of skin biopsy in the differential diagnosis of young patients with clinically refractory epilepsy, myoclonus, and cognitive decline.

Clinicopathologic and Molecular Analysis of Inflammatory Pseudotumor-Like Follicular/Fibroblastic Dendritic Cell Sarcoma: A Case Report and Review of Literature

Bryan MORALES-VARGAS, Kristin DEEB, Deniz PEKER — 2021-09-01

Inflammatory pseudotumor-like follicular/fibroblastic dendritic cell (FDC/FRC) sarcoma is an extremely rare neoplasm of the spleen associated with EBV and characterized by spindle cell morphology, dense mixed chronic inflammatory background, and a broad immunophenotypic profile often causing a diagnostic challenge for pathologists. The molecular features of FDC/FRC sarcoma are largely unknown due to a lack of comprehensive data. Here we present the results of next-generation sequencing and Single Nucleotide Polymorphism Copy Number array analysis in a case of FDC/FRC and review the literature.

Turkish Journal of Pathology - 2021; 37(3)

What�s in a Name? Michael N. Marsh, BTh, DPhil, DM, DSc, FRCP

The Role of Immunocytochemical Markers to Differentiate Primary from Secondary Neoplastic Hepatic Masses: A Diagnostic Challenge on Cytology

Metastases to the Stomach: Clinicopathologic Features of Metastases Mimicking Gastric Primaries

Cholemic Nephrosis: An Autopsy Study of a Forgotten Entity

Peripheral Lymphadenopathy in Children: Cytomorphological Spectrum and Interesting Diagnoses

What Would Next Generation Sequencing Bring to the Diagnosis and Treatment of Sarcomas? A Series of 20 Cases, a Single Institution�s Experience

Does the Distance of the Tumor from the Surgical Margin Affect Biochemical Recurrence in Patients with Pathological Organ-Confined Prostate Cancer?

Prognostic and Predictive Significance of PD-L1 Expression in Non-Small Cell Lung Cancer Patients: A Single-Center Experience

Primary Myeloid Sarcoma of Ovary: A Case Report and Review of the Literature

Cysts that Still Persist: A Case Series of Cysticercosis on Histopathological Evaluation

Giant IgG4-Related Pseudotumor of the Esophagus Resected with Endoscopic Submucosal Dissection: A Case Report and Review of the Literature

A Case of Lafora Disease Diagnosed by Axillary Skin Biopsy

Clinicopathologic and Molecular Analysis of Inflammatory Pseudotumor-Like Follicular/Fibroblastic Dendritic Cell Sarcoma: A Case Report and Review of Literature