Gaurav Pratap Singh Gahlot

Intraosseous primary malignant peripheral nerve sheath tumor of the calcaneus: an unusual case and review of literature.

Malignant peripheral nerve sheath tumors (MPNSTs) are uncommon sarcomas that originate from a peripheral nerve or neurofibroma either spontaneously or in association with neurofibromatosis type 1. MPNSTs account for approximately 5% of all soft tissue malignancies. The tumor is commonly seen in the extremities and trunk. Most of these tumors are high-grade with the potential to recur and metastasize. Common metastatic sites include the lungs, bone, and pleura. Primary intraosseous MPNST is rare, and the diagnosis of intraosseous MPNST, especially in an unusual location is difficult because of its cellular origin, histomorphological similarities with other sarcomas, and bone is the most common site for metastasis. We report an unusual case of MPNST of the calcaneus in a young male.

Cathepsin L and B as Potential Markers for Liver Fibrosis: Insights From Patients and Experimental Models

OBJECTIVES: Cathepsin L (CTSL) and B (CTSB) have a crucial role in extracellular matrix (ECM) degradation and tissue remodeling, which is a prominent feature of fibrogenesis. The aim of this study was to determine the role and clinical significance of these cathepsins in liver fibrosis. METHODS: Hepatic histological CTSL and CTSB expression were assessed in experimental models of liver fibrosis, patients with liver cirrhosis, chronic viral hepatitis, and controls by real‐time PCR and immunohistochemistry. Plasma levels of CTSL and CTSB were analyzed in 51 liver cirrhosis patients (Child–Pugh stages A, B and C) and 15 controls. RESULTS: Significantly enhanced CTSL mRNA (P=0.02) and protein (P=0.01) levels were observed in the liver of carbon tetrachloride‐treated mice compared with controls. Similarly, hepatic CTSL and CTSB mRNA levels (P=0.02) were markedly increased in Abcb4−/− (ATP‐binding cassette transporter knockout) mice compared with wild‐type littermates. Elevated levels of CTSL and CTSB were also found in the liver (P=0.001) and plasma (P<0.0001) of patients with hepatic cirrhosis compared with healthy controls. Furthermore, CTSL and CTSB levels correlated well with the hepatic collagen (r=0.5, P=0.007; r=0.64, P=0.0001). CTSL and CTSB levels increased with the Child–Pugh stage of liver cirrhosis and correlated with total bilirubin content (r=0.4/0.2; P≤0.05). CTSL, CTSB, and their combination had a high diagnostic accuracy (area under the curve: 0.91, 0.89 and 0.96, respectively) for distinguishing patients from controls. CONCLUSIONS: Our data demonstrate the overexpression of CTSL and CTSB in patients and experimental mouse models, suggesting their potential as diagnostic biomarkers for chronic liver diseases.

Solid pseudopapillary neoplasm of the ovary with metastases to the omentum and regional lymph nodes

Extrapancreatic solid pseudopapillary neoplasms (SPNs) are rare tumors, which bear morphological, immunohistochemical, and molecular features similar to those of pancreatic counterparts. SPN occurs primarily in adolescent girls and young women. It is considered to be a malignant neoplasm with low-grade biology. Ovarian SPNs are uncommon, have benign morphology, usually limited to the ovary and local surgical excision is curative. We report an unusual case of SPN of right ovary with extraovarian spread and metastases to lymph nodes. To the best of our knowledge, this is the second documented case of extragonadal spread of ovarian SPN.

Patients with mild enteropathy have apoptotic injury of enterocytes similar to that in advanced enteropathy in celiac disease

BACKGROUND Severity of villous atrophy in celiac disease (CeD) is the cumulative effect of enterocyte loss and cell regeneration. Gluten-free diet has been shown to benefit even in patients having a positive anti-tissue transglutaminase (tTG) antibody titre and mild enteropathy. AIM We explored the balance between mucosal apoptotic enterocyte loss and cell regeneration in mild and advanced enteropathies. METHODS Duodenal biopsies from patients with mild enteropathy (Marsh grade 0 and 1) (n=26), advanced enteropathy (Marsh grade ≥2) (n=41) and control biopsies (n=12) were subjected to immunohistochemical staining for end-apoptotic markers (M30, H2AX); markers of cell death (perforin, annexin V); and cell proliferation (Ki67). Composite H-scores based on the intensity and distribution of markers were compared. RESULTS End-apoptotic markers and marker of cell death (perforin) were significantly up-regulated in both mild and advanced enteropathies, in comparison to controls; without any difference between mild and advanced enteropathies. Ki67 labelling index was significantly higher in crypts of mild enteropathy, in comparison to controls, suggesting maintained regenerative activity in the former. CONCLUSIONS Even in patients with mild enteropathy, the rate of apoptosis is similar to those with advanced enteropathy. These findings suggest the necessity of reviewing the existing practice of not treating patients with mild enteropathy.

Interpretation of ileal biopsies

The ileum is one of the most common sites of intestine to undergo endoscopic biopsy. However, even with the experienced histopathologists, a definite diagnosis can be achieved only in 18% cases. Lack of knowledge about proper tissue handling, tissue orientation, overlapping histological findings, and lack of a standard algorithm based approach results in this low diagnostic yield. In this review article, we have tried to discuss these aspects and give a clear picture how to approach the ileal lesions. It would help the surgical pathologists in effectively interpreting the lesions and to identify the common pitfalls.

Histological assessment & use of immunohistochemical markers for detection of dysplasia in Barrett’s esophageal mucosa

BACKGROUND Histological assessment of dysplasia in Barretts esophagus (BE) has high inter-observer variability. Hence, use of ancillary markers for early detection of dysplasia in BE is an important clinical question. METHODS In this retrospective study consecutive cases of BE (n = 59), over a period of 4 years were included. Hematoxylin and eosin stained sections were reviewed independently by 3 senior qualified pathologists, who graded the dysplasia according to the Vienna Classification system and inter-observer agreement was analysed using the Kappa statistics. Subsequently Alpha-Methyl Acyl-CoA Racemase (AMACR), p53, CyclinD1, β-catenin, H2AX and M30 immunohistochemical (IHC) stains were examined on the following disease categories: BE with no dysplasia [NFD] (45), BE with indefinite for dysplasia (IFD) (4), low grade dysplasia (LGD) (3), high grade dysplasia (HGD) (2) and in adenocarcinomas (5). H score was calculated by adding up products of different grades of stain distribution and stain intensities (range of scores 0-300). RESULTS Among the 3 pathologists, overall agreement was poor (k 0.06; 95% CI -0.089 to 0.145), with highest disagreement noted for differentiating the LGD and IFDs (k = 0.21). After revising the histological criteria, the kappa improved to 0.53. Among the IHC stains performed, p53, β-catenin, H2AX and M30 stains were significantly useful to differentiate between IFD and LGD (P values: 0.04, 0.004, 0.05 & 0.04, respectively). AMACR and β-catenin stains though were up-regulated in HGD/adenocarcinomas than in other categories, their expression were not statistically different between the IFD and LGDs. CONCLUSIONS A detail histological scoring system may bring uniformity in histological interpretation of dysplasia in BE. Using a combined panel of IHC stains seems helpful in detection of dysplasia in BE, especially to differentiate the IFD and LGD changes in BE.

Angiomyomatous hamartoma of lymph nodes: Clinicopathological study of 6 cases with review of literature

Angiomyomatous hamartoma (AMH) is a rare disease with predisposition for inguinal and femoral lymph nodes. Histologically, it is characterized by replacement of lymph nodal parenchyma with irregularly distributed thick walled blood vessels, haphazardly arranged smooth muscle cells, variable amount of fat and fibrous tissue in a sclerotic lymphatic stroma. Few cases have also been reported in popliteal and sub - mandibular location. The exact pathogenesis is still not known. Although this entity is very rare, its recognition is important in discriminating it from other benign and malignant vascular lesions of lymph nodes.

Immunohistochemical Expression of Antitissue Transglutaminase 2 in Tissue Injuries: An Interpretation Beyond Celiac Disease

Tissue transglutaminase 2 enzyme plays a diverse role in intracellular and extracellular functioning. Aberrant expression of anti-TG2 antibody has recently been proposed for extraintestinal identification of celiac disease (CeD), but its utility is questionable. To examine whether anti-TG2 immunohistochemical (IHC) staining can be of diagnostic value in identifying extraintestinal involvement in CeD, tissue blocks of patients with IgA nephropathies (IgAN), minimal change disease, membranous glomerulonephritis, membrano-proliferative glomerulonephritis, normal kidney, intestinal biopsies from CeD, tropical sprue, nonspecific duodenitis, and inflammatory bowel disease; liver biopsies from patients with chronic hepatitis B and C, acute liver failure (ALF), and CeD-associated liver diseases were retrieved and subjected to IHC staining for anti-tissue transglutaminase 2 enzyme. H-score was calculated by multiplying the area of positivity and stain intensity. Anti-TG2 stain H-scores were almost similar in IgAN and non-IgANs (H-score 6.31±3 vs. 7.03±2.7); however, H-scores in both of these groups were significantly higher than in normal renal parenchyma (1.6±1.5). Only 6.2% patients with IgAN with anti-TG2 immunostain positivity showed a positive anti-tTG antibody serology and villous abnormalities, suggestive of CeD. Intestinal biopsies from patients with CeD, tropical sprue, nonspecific duodenitis, and inflammatory bowel disease also showed high anti-TG2 H-scores, with no statistically significant differences. Liver biopsies from patients with both ALF, as well as chronic liver diseases showed high anti-TG2 H-scores; with highest stain expression in ALF. In conclusion, IHC expression of anti-TG2 stain correlates with both acute and chronic tissue injuries, irrespective of etiology and organ involvement. It is not a reliable marker for diagnosis of CeD.

A Diagnostic Conundrum: A Rare Cause of Abdominal Distension in a Preterm Neonate.

To the Editor: We would like to highlight that, although uncommon, the surgical causes of abdominal distension in neonates need to be diagnosed and treated early. An ileo-ileal intussusception (INT), causing abdominal distension is very rare. The surgical management may further be complicated by systemic infections, to which these preterm neonates are prone [1, 2]. Herein we report a preterm (25 wk+5 d) male child with low APGAR scores, born by vaginal delivery to a fourth gravida mother (G4L1A2). In the intensive care, he was doing well, until the 4th post natal day, when he developed hyperbil irubinemia, bil ious vomiting, abdominal distension, apnea, bradycardia, thrombocytopenia, acidosis, constipation and shock. With abdominal X-ray, dilated bowel loops were seen and a provisional diagnosis of necrotizing enterocolitis (NEC) with septic shock was made (Fig. 1a). However, his condition deteriorated and on the 8th day he passed away. On autopsy, the child had no gross abnormality (weighed 690 g). Bilateral pneumonia was found along with an ileo-ileal INTof 0.5 cm length, lying approximately 20 cm proximal to the ileo-cecal junction (Fig. 1b). No perforation, gangrene, features of intestinal atresia, stenosis or myopathy was identified (Fig. 2f–j). In addition,invasive budding yeasts and pseudohyphae, consistent with Candida sp., were noted in all organs (Fig. 2a–e), confirmed by the periodic acid Schiff and silver methinamine stains. The cause of abdominal distension in this case was finally attributed to disseminated fungal sepsis with the ileo-ileal INT as a complicating factor. In neonates the acquired causes of abdominal distension are: necrotizing enterocolitis (NEC), followed by sepsis, intestinal atresia, malrotation-volvulus, meconium ileus and Hirschsprung disease [1, 2]. Ileo-ileal INT, is uncommon (<1 % of all intussusception) [3]. The importance of distinguishing INT from NEC, lies in different managements offered. Pathogenesis of the former is poorly understood; intestinal dysmotility/ atresia, hypo-perfusion/ hypoxia, or use of prostaglandin analogues have been suggested [4]. This case is being highlighted to emphasize the need to rule out a surgical abdomen with appropriate radiological tools when conservative management fails. However, systemic infections, as Candida tropicalis, which is commonest in these incredibly S. Ghosh : B. Gupta :M. Singh :G. P. S. Gahlot : P. Das (*) Department of Pathology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110029, India e-mail: prasenaiims@gmail.com

A unique anal hepatoid adenoma in a human.

two layers were not separated, this intensity difference was not seen. PAS staining is used for the detection of structures that contain high concentrations of carbohydrate macromolecules. We supposed that the PDL contained less glycogen than DM when they became separated. Further study is needed to determine whether this is a direct cause of the split. Collagen fibres of the two layers were analysed with immunofluorescence staining. The PDL seemed to contain more type I collagen fibrils with stronger staining intensity than the corneal stroma and DM (Figure 2Bb,Cb). The staining intensity for type IV collagen fibrils in the PDL was a little stronger than that in DM, but much denser than in the corneal stroma, indicating that the PDL contained more type IV collagen than the stroma (Figure 2Ba,Ca). This finding indicated that the PDL, as the interlayer between the stroma and DM, has a different collagen composition from that of the stroma and that of the DM. The penetration of fungi through the PDL and DM was not the cause of the split (Figure 1Ca). The PDL and DM were intact, although a heavy fungal load could be seen penetrating the posterior cornea. The PDL–DM split was mainly caused by fungus-related inflammation. According to our observation, most PDL–DM split cases had inflammatory cells infiltrating the posterior one-quarter of the corneal stroma, and the inflammation in the posterior part was always severe in degree (Figure 1Cb). Cases without a PDL– DM split showed clear posterior stroma, with the inflammation limited to the anterior stroma (Figure 1Cc). So far, the PDL–DM split has been found only in cases of fungal keratitis. Other infectious corneal diseases, such as bacterial and amoebic keratitis, also cause severe inflammation throughout the stroma, but the PDL and DM remain intact. Our observation confirmed that the PDL–DM split was more likely to be associated with the special inflammatory reaction caused by fungi. The damage to the connections between the PDL and DM was possibly attributable to the inflammatory mediators rather than resulting from a direct impact of agent factors.