Turkish Journal of Pathology - 2022; 38(1)

Clinico-Histological Features of Thrombotic Microangiopathy in Renal Biopsies: A Retrospective Study

Niraimathi MANICKAM, Vinita AGRAWAL, Pallavi PRASAD, Manoj JAIN, Narayan PRASAD — 2022-01-01

Objective: Thrombotic microangiopathy (TMA) is often first detected on a renal biopsy performed for renal manifestations. Apart from hemolytic uremic syndrome (HUS) and thrombotic thrombocytopenic purpura, there are various secondary conditions associated with TMA. This study analyzes the clinico-pathological spectrum, etiological factors and renal outcome of TMA diagnosed on renal biopsy. Material and Method: A retrospective evaluation of renal biopsies for TMA over 5.5 years was performed. Clinical and laboratory data was collected from patient records. Results: A total of 40 biopsies from 39 patients showed TMA comprising 33 native and 7 transplant biopsies. Malignant hypertension (n=13) was the most common etiology in native biopsies followed by postpartum TMA (n=7), atypical HUS (aHUS) (n=7), and lupus nephritis (n=6). TMA in transplant biopsies was due to acute rejection (n=4) and CNI toxicity (n=3). Serum creatinine was high in most patients (mean 5.6 + 2.5 mg/ dl). aHUS showed the highest mean LDH levels and the lowest average platelet counts. Renal biopsies in malignant hypertension and postpartum TMA showed isolated arterial changes while aHUS and lupus nephritis showed both glomerular and arterial involvement. Postpartum TMA and aHUS had poor renal outcome requiring renal replacement therapy. Conclusion: Most postpartum TMA and aHUS had systemic features of TMA while malignant hypertension and lupus nephritis showed �isolated renal TMA�. This emphasizes the importance of careful evaluation of renal biopsies even in the absence of systemic features of TMA.

Utility of P63 in Differentiating Giant Cell Tumor from Other Giant Cell-Containing Lesions

2022-01-01

Objective: To assess P63 expression in giant cell-containing lesions of the bone (GCLB) and to determine its utility in differentiating giant cell tumor of the bone (GCTB) from other GCLBs. Material and Method: Cases diagnosed as GCLB on histopathology were included in the study. P63 immunohistochemistry was performed in all the cases. The percentage of cells showing nuclear positivity was assessed in the non-giant cell component. Statistical analysis was performed using the Mann-Whitney U test. Results: Of the total 53 cases studied, the majority were GCTBs (23), followed by 12 cases of chondroblastomas (CBL) and 18 other giant cell lesions (GCLs). All giant cell-containing lesions except one case of CBL and brown tumor of hyperparathyroidism (BTH) showed P63 staining in the non-giant cell component. However, the mean P63 labeling of GCT (52.6%) was higher compared to CBL (28.3%), aneurysmal bone cyst (ABC) (15.2%), non-ossifying fibroma (NOF) (24.5%), giant cell lesion of small bones (GCLSB) (11%), BTH (6.8%) and chondromyxoid fibroma (CMF) (12.3%), with a p-value of <0.001. Conclusion: Although p63 was present in majority of the GCLBs, its percentage positivity was significantly higher in GCTB compared to the other GCLBs. The diagnosis of GCTB is likely if cut-off value of >50% is applied.

Detection of ALK Gene Rearrangements in Non-Small Cell Lung Cancer by Immunocytochemistry and Fluorescence in Situ Hybridization on Cytologic Samples

2022-01-01

Objective: Determination of the molecular status is mandatory for personalized treatment of patients with non-small cell lung carcinoma. The present study was performed to detect anaplastic lymphoma kinase (ALK) rearrangements in pulmonary adenocarcinoma on cytology samples, using immunocytochemistry (ICC) and fluorescence in situ hybridization (FISH) on cell-blocks to assess the diagnostic reliability of these two techniques. Material and Method: A total of 50 confirmed lung adenocarcinoma cases were included. In all the 50 cases, ICC was performed for ALK protein expression by using the D5F3 clone on Ventana platform. On the basis of ALK protein expression on ICC, the cases were categorized as ALK positive (2+ or 3+ strong cytoplasmic granular positivity) or negative (negative or 1+ cytoplasmic granular positivity). FISH for detection of ALK gene rearrangement was performed in 7 ALK ICC positive cases and 7 ALK ICC negative cases using the Vysis ALK break apart FISH probe kit. Results: Based on ICC, 7(14%) cases were ALK positive and 43(86%) were ALK negative. ALK gene rearrangements in lung adenocarcinoma were more commonly seen in non-smokers (31.25%) as compared to smokers (6.25%). Among the ALK-ICC positive cases, FISH demonstrated break apart signal in 5 cases (ALK- ICC positive); however, no break-apart signals were seen in 2 ALK-ICC positive and all the seven ALK-ICC negative cases. Conclusion: Immunocytochemistry on cell- blocks using DF53 clone is a highly sensitive and specific method for the detection of ALK gene rearrangements in lung adenocarcinoma with a greater number of ALK positive cases being detected on ICC as compared to the ALK-FISH.

Calreticulin Immunohistochemistry in Myeloproliferative Neoplasms - Evolution of a New Cost-Effective Diagnostic Tool: A Retrospective Study with Histological and Molecular Correlation

Sanjeet ROY, Marie Therese MANIPADAM, Poonkuzhali BALASUBRAMANIAN — 2022-01-01

Objective: Recent WHO 2017 guidelines mandates mutational analysis for the diagnosis of myeloproliferative disorders (MPN). JAK2V617F has been found in only 50-60% of Primary myelofibrosis (PMF) and Essential thrombocythaemia (ET). A recently discovered somatic Calreticulin (CALR) mutation has been linked to MPN. This mutation leads to a common 36 amino acid C-terminus that can be detected accurately by immunohistochemistry (IHC). Limited published literature exists on the utility of CAL2IHC as a diagnostic tool. The study aimed to validate the sensitivity and specificity of CAL2IHC for its use as a cost effective and rapid diagnostic tool. Material and Method: Subjects included 23 patients of MPN (15 PMF, 6 ET, 2 PV (Polycythaemia Vera)), diagnosed between January 2014 to November 2016 with adequate available tissue for histopathological and mutational analysis. Mutational analysis had been performed with Bidirectional Sanger sequencing. CAL2IHC was performed in all cases and the sensitivity and specificity of CAL2 IHC to identify the Calreticulin mutation was evaluated with respect to comparison with the gold standard mutation analysis. Results: In the 23 MPN patients, CAL2 IHC detected CALR mutation with a sensitivity of 95% and a specificity of 100%. Both cases of PV were negative for CAL2IHC. CAL2IHC showed cytoplasmic positivity in ET (2-3+) and PMF (1-3+) with (62-69%) positive megakaryocyte staining. All 6 ET cases and all 14/15 PMF cases were CAL2IHC positive, and these results were concordant with CALR mutational analysis. Conclusion: Anti-CAL2 immunohistochemistry is a specific and a sensitive marker to detect CALR mutation. Its� cost effectiveness and fast results are quite advantageous as compared to molecular analysis.

Diagnostic Discrepancies Between Intraoperative Frozen Section and Permanent Histopathological Diagnosis of Brain Tumors

2022-01-01

Objective: Intraoperative frozen section (IOFS) diagnosis of brain tumors plays an important role in assessing the adequacy of the sample and determining the treatment plan. The aim of this study was to investigate the diagnostic accuracy between IOFS and permanent sections. Material and Method: The authors reviewed the histopathological results of 383 brain tumors, including IOFS and permanent histological diagnosis. The cases were classified into three diagnostic compatibilities (i) Perfect fit; the diagnosis of IOFS was identical to the permanent diagnosis, (ii) Partial compatibility; IOFS diagnosis was not incorrect but was too broad to be considered full compatibility, (iii) Conflict; IOFS diagnosis is completely different from the permanent diagnosis. The permanent diagnosis was used as a primary criterion and was compared to IOFS diagnosis and recurrence rate using different statistical methods. Results: 84% of the patients underwent craniotomy and tumor resection, while 15% only underwent tumor biopsy. Approximately, 53.8 % of the cases revealed perfect matching in the diagnosis between IOFSs and permanent sections, while 16.2% of the cases revealed complete mismatching in the diagnosis between the sections. The remaining 30% of the cases showed partial compatibility in the diagnosis between the two diagnostic methods. There was no significant difference in recurrence rate among all cases of different diagnostic compatibility (p=0.54). Conclusion: There is a diagnostic discrepancy between IOFSs and permanent sections. However, cases that revealed no consensus in the diagnoses showed no negative effect on the patient outcome. Further studies should be conducted to explore the reasons of this conflict in the two diagnostic methods.

Granulomatous Mastitis: A Clinical and Diagnostic Dilemma

2022-01-01

Objective: Granulomatous mastitis (GM) is a challenging inflammatory disorder of the breast. In this study we aimed to present the detailed clinical and morphological features of GM cases, diagnostic clues for specific and idiopathic etiologies, the difficulties in evaluating trucut biopsies, and the results of different therapeutic approaches. Material and Method: We retrospectively analysed the clinical, radiological and morphological features of 114 GM cases diagnosed with fine needle aspiration, and trucut, incisional, and excisional biopsy. Results: The mean age was 35.8. Only eight cases were older than 45 years. Bilateral involvement was observed in 4 (3.5%) cases. The most common clinical symptoms were breast mass/abscesses, tenderness, and skin changes. Microbiological culture was positive in 4 cases for gram-positive bacteria. Only 3 cases showed a positive tuberculin/PCR test for tuberculosis. The major USG finding was a hypoechoic well-defined or ill-defined mass/abscess; MRI finding was heterogeneous non-mass contrast enhancement. Cases diagnosed with cytology (35 cases) did not have breast malignancy either in their history or clinical follow up period. Fine needle aspiration cytology materials revealed epitheloid granulomas mixed with neutrophils, lymphocytes accompanied by giant cells, and suppurative necrosis. Histopathological reevaluation of 65 trucut/incisional/ excisional biopsies revealed granuloma formation in 65 (100%), Langhans type giant cells in 59 (90.7%), microabscess formation in 41 (63%), caseous necrosis in 1 (1.5%), neutrophilic cysts in 30 (46.1%), eosinophilic infiltration in 48 (73.8%), interlobular inflammation in 14 (21.5%), fat necrosis in 5 (7.6%), ductal ectasia in 6 (9.2%), and lactational changes in 4 (6.1%) cases. Granulomas were lobulocentric in 58 cases, foreign body type/fat necrosis-related in 6 case, and periductular in 1 case. Cystic neutrophilic granulomatous mastitis was observed in one case. We also evaluated the histochemical stains of these 65 biopsies. Only one sample was positive for acido-resistant bacilli (ARB) by the EZN method and one sample was positive for gram-positive bacilli by gram stain. Conclusion: Small, superficial trucut biopsies may cause difficulties in determining the etiology and differential diagnosis of granulomatous mastitis. For optimal management and timing the appropriate therapy, the ideal biopsy procedure, special stains, and a multidisciplinary team consisting of the surgeon, pathologist, and radiologist are the most important issues.

Mesenchymal Tumors Involving the Pancreas: A Clinicopathologic Analysis and Review of the Literature

Gokce ASKAN, Olca BASTURK — 2022-01-01

Objective: Most pancreatic tumors are epithelial, and, among these, more than 90% are of ductal origin. However, a variety of mesenchymal tumors may involve the pancreas and may manifest different clinicopathological characteristics. The literature on mesenchymal tumors in the pancreas is largely limited to individual case reports or analyses of small series, predominantly focusing on radiologic features. Material and Method: Authors� institutional and consultation databases were reviewed to identify the mesenchymal tumors involving the pancreas. Results: Forty cases were identified; twenty-five (63%) tumors were benign/borderline, and the remaining fifteen (37%) were malignant. Of the benign/borderline tumors; 9 were solitary fibrous tumors, 6 gastrointestinal stromal tumors (GISTs), 4 schwannomas, 2 desmoid type fibromatosis, 1 lymphangioma, 1 ganglioneuroma, 1 inflammatory myofibroblastic tumor, and 1 low grade mesenchymal neoplasm. Malignant tumors included 6 cases of leiomyosarcomas, 4 liposarcomas, 2 rhabdomyosarcomas, 1 epithelioid angiosarcoma, 1 malignant peripheral nerve sheet tumor, and 1 undifferentiated pleomorphic sarcoma. Four cases (multicystic schwannoma, desmoid fibromatosis, lymphangioma and inflammatory myofibroblastic tumor) were preoperatively misdiagnosed as a primary epithelial tumor of the pancreas. Conclusion: Mesenchymal tumors rarely involve the pancreas. They are usually benign/borderline neoplasms but may be diagnostically challenging, especially clinically/radiologically, as they may form cystic and/or large lesions in the pancreas. Mesenchymal tumors should be considered in both the clinical/radiological and pathological differential diagnosis of pancreatic lesions.

Secondary Localized Cutaneous Amyloidosis is not Rare in Bowen�s Disease and Bowenoid Papulosis

2022-01-01

Secondary localized cutaneous amyloidosis is a histopathological finding seen in the dermis, in various benign, premalignant, and malignant skin conditions, without clinical significance. The real incidence is not known. We aimed to investigate the phenomenon of secondary localized cutaneous amyloidosis in Bowen�s disease and Bowenoid papulosis. We retrospectively evaluated the data of all cases with histopathological confirmation of Bowen�s disease and Bowenoid papulosis between 2006 and 2017 in our Dermatovenereology and/or Pathology departments. Secondary localized cutaneous amyloidosis was observed in three patients with Bowen�s disease (3/52; 5.8%) and in three patients with Bowenoid papulosis (3/18; 16.7%). Herein, we present the demographic, clinical and histopathological features of these six cases of secondary localized cutaneous amyloidosis in detail. Although the occurrence of secondary localized cutaneous amyloidosis in epithelial tumors is a well-known phenomenon, its incidence has not been previously reported in Bowen�s disease and Bowenoid papulosis. Therefore, our results indicating a high incidence may be particularly important for Bowenoid papulosis, as its association with secondary localized cutaneous amyloidosis has only been shown in one case before. Moreover, in three of six cases, we histologically observed areas of regression with a marked prominence of amyloid deposition. Remarkably, two of these patients had a history of topical application of destructive agents which reveals a possible etiologic relationship between secondary localized cutaneous amyloidosis and cellular apoptosis/necrosis induced by these external agents.

Eosinophilic Solid and Cystic Renal Cell Carcinoma: From Unclassified to Classified, A Case Report

2022-01-01

Eosinophilic solid and cystic renal cell carcinoma (ESC RCC) is a novel tumour with unique morphological and immunohistochemical features. It is a recently described entity after the 2016 World Health Organization Classification of Tumours of the Urinary System and Male Genital Organs and is characterised by a solid cystic tumour composed of polygonal cells with voluminous eosinophilic cytoplasm and CK20 positivity. This tumour has uncertain malignant potential and also has an association with tuberous sclerosis complex (TSC). Sarcomatoid differentiation has not been reported in ESC RCC till now. ESC RCC poses a diagnostic challenge as many eosinophilic/oncocytic renal tumours are included in the differentials. We present a case of ESC RCC with sarcomatoid differentiation in an elderly female without any clinical features of TSC and discuss the differential diagnosis of oncocytic renal tumours.

Apple Peel Deformity and Malrotation of Gut: Autopsy Findings of a Rare Cause of Mortality in Utero

Deepti MUTREJA, Sharanjit SINGH — 2022-01-01

One-third of all intestinal obstructions in the newborn are caused by atresias. The most common site is the duodenum followed by jejunoileal and colonic locations. Herein we report the autopsy findings of a rare case of jejunoileal atresia associated with malrotation of gut. Autopsy performed on a 36 weeks old male fetus still birth, born of a non-consanguineous marriage, demonstrated jejunoileal atresia with apple peel deformity and malrotation of gut. Although the diagnosis was established in the prenatal period, in utero fetal demise occurred before definitive surgical intervention could be done. This case highlights the importance of early diagnosis and intervention.

An Unusual Nodular Tumour of the Penile Shaft with Clinicopathologic and Immunohistochemical Correlation

Poonam Abhay ELHENCE, Deepak VEDANT, Saurabh SINGH, Puneet PAREEK — 2022-01-01

Granular cell tumours are uncommon acquired benign tumours of nerve sheath origin that are usually seen in the head and neck region and upper aero-digestive tract. They usually present as solitary small sized nodules in middle age. The tumour is usually benign and composed of sheets of large sized cells with abundant granular cytoplasm containing lysosomal macro-inclusions known as pustulo-ovoid bodies of Milian (POB) that represent the heterogeneity of the lysosomes. No well-established criteria for malignancy have been described for this tumour. In this article, we have discussed a rare case of granular cell tumour of the penis with its characteristic histomorphology and immunohistochemistry and relevant differential diagnosis.

Multifocal Pseudomyogenic Hemangioendothelioma Involving the Scalp and Nose, Misdiagnosed as A Sarcoma: A Rare Case Report

2022-01-01

This case report aims to present clinicopathological features of an extremely rare case of multifocal pseudomyogenic hemangioendothelioma (PMHE) in the scalp. A 21-year-old male developed multiple, focally ulcerated, nodules over the root of his nose and scalp. One of the skin lesions was sampled at another dermatology clinic, where this was diagnosed as a sarcoma. A review of biopsy sections showed well-circumscribed dermal lesions, comprising plump spindle and epithelioid cells, mimicking rhabdomyoblasts. Immunohistochemically, tumor cells were positive for AE1/AE3, CD31, FLI-1 and ERG. INI-1 was retained. A diagnosis of PMHE was offered. Subsequently, the patient underwent wide excision and has been asymptomatic for 8 months, post-surgery. PMHE is rarely reported in the head and neck region, where it can constitute a diagnostic pitfall. Awareness of this tumor and appropriate immunohistochemical stains are necessary for its timely diagnosis, in order to avoid radical treatments. A review of similar, previously documented cases is presented.

The Histopathologic Examination of a Second Muscle Biopsy Specimen at a Later Date may Sometimes be the Best Approach to Make a Differential Diagnosis in Neuromuscular Disorders

Gulden DINIZ, Berk OZYILMAZ, Sarenur GOKBEN — 2022-01-01