Oxcarbazepine-induced toxic epidermal necrolysis in lupus erythematosus: Turning into a "frequent" rarity but is it diagnosing that matters?

Classic Toxic Epidermal Necrolysis (TEN) in Lupus Erythematosus (LE) is rare and that caused by oxcarbazepine is even rarer. It can be triggered/induced by various insults, the most prominent being drugs. Herein, we describe a young female, a diagnosed case of LE with lupus nephritis, with recent-onset central nervous system vasculitis (incidentally detected on neuroimaging while she was being evaluated for a recent-onset behavioural change), who within a month of exposure to the drug developed an extensive exfoliating skin rash with mucosal lesions, which on histopathological evaluation showed TEN in LE, triggered by Oxcarbazepine, which was commenced for seizure prophylaxis. She was managed with pulse methylprednisolone, followed by intravenous immunoglobulin (IVIg), after which she made a satisfactory recovery. It is highlighted that TEN in LE patterns must be recognized in an emergency and Acute Syndrome of Apoptotic Panepidermolysis (ASAP) concept applied promptly without awaiting diagnoses. Further, many common drugs possibly trigger this pathology making the rara-avis not rare anymore!

DRESS, the maverick among SCARS: A case series-based review of literature.

DRESS is a potentially life-threatening severe cutaneous adverse reaction (SCAR). Historically, it was most frequently linked with phenytoin and was initially described as phenytoin hypersensitivity syndrome; however, it was later found to be caused by various other medications, with the commonest been aromatic anticonvulsants, allopurinol and sulfonamides. The severity of this entity is related to systemic involvement, which can result in multiorgan failure and death. The diagnosis of DRESS, especially in the early stages, remains challenging and elusive due to its heterogeneous clinical presentation and the complex course of the disease with different patterns depending on the causal drug. The most important step in the management of DRESS is early diagnosis and immediate cessation of the suspected offending drug along with oral steroids or immunosuppressants to control the disease. We describe the varying presentation and management of six adults with DRESS from a tertiary care hospital, observed over a two-year period with a brief review of the literature.

Influence of Interstitial Cells of Cajal in Congenital Ureteropelvic Junction Obstruction.

BACKGROUND: The etiopathogenesis of congenital ureteropelvic junction obstruction (UPJO) has been inconclusive in spite of the numerous studies carried out to find the possible causative factor. The results of different studies have been conflicting and contradictory. It has been postulated that the interstitial cells of Cajal (ICC) are the pacemaker cells located in the ureteropelvic junction (UPJ) and regulate the peristalsis in this region. Paucity of these cells may be one of the causative factors for congenital UPJO although there is no clear consensus on this issue. Therefore, the present study has been carried out to ascertain the role of ICC as one of the possible etiological factors for congenital UPJO. The aim of this study is to first identify the presence of ICC at UPJ, second to compare the average number of ICC in congenital UPJO with a control population without UPJO, and third to ascertain whether any correlation exists between the number of ICC and postoperative improvement in function of the affected kidney. MATERIALS AND METHODS: A total number of 30 patients who underwent dismembered Anderson-Hynes pyeloplasty for congenital UPJO between June 2016 and November 2017, were compared with seven controls who underwent nephroureterectomy for various other reasons. The specimen was subjected to immunohistochemistry (IHC), and a quantitative comparison was made for the ICC between cases and controls. The preoperative and postoperative function was evaluated by renal diuretic scintigraphy. RESULTS: The disease was more common among males in the ratio of 6.5:1, and there was a predominance of the left-sided involvement. In the studied cases, the average number of ICC seen for every high-power field (hpf) was 4.86 ± 0.76/hpf, whereas in control it was 11.74 ± 0.86/hpf (P = 0.04). The postoperative outcome, as measured by the improvement in split renal function, did not have any correlation with the number of ICC. CONCLUSION: The ICC are present at the UPJ and can be detected by immunohistochemistry due to their CD117 positivity. These cells are significantly low at this site in cases of congenital UPJO when compared to controls without any obstruction. The number of ICC bears no correlation to the postoperative improvement in function.

Epithelioid hemangioma of distal femoral epiphysis in a patient with congenital talipes equinovarus.

BACKGROUND: Epithelioid hemangioma (EH) is a rare benign vascular lesion of soft tissue and bone, characterized by endothelial cells with epithelioid or histiocytoid appearance. Though tubular bones, flat bones, vertebra and short bones are common sites for this lesion, the epiphyseal involvement is extremely rare. We present an unusual case of EH of the distal femur in a young boy. CASE REPORT: A 12-year-old boy who had congenital talipes equinovarus of the right foot presented with progressively increasing pain in the right lower thigh for six months. Physical examination revealed muscular atrophy of the right lower limb and a moderately tender swelling in the medial aspect of the right knee without restriction of knee movement. An X-ray revealed an osteolytic lesion, which appeared iso- and hypointense on T1W and hyperintense on T2W MRI images in the distal epiphysis and adjacent metaphysis of the right femur. A radiological diagnosis of chondroblastoma was entertained. The patient was treated with curettage and bone grafting. Histopathology showed a tumor composed of thin-walled arteriolar capillaries lined by large, polyhedral epithelioid endothelial cells with vesicular nuclei, finely distributed nuclear chromatin, and moderate amount of eosinophilic cytoplasm. The endothelial cells were strongly immunopositive for CD34. Mitotic activity was low and the Ki-67 proliferative rate was <2%. A diagnosis of EH was made. EH is a benign lesion and it should be differentiated from its histologically similar malignant counterparts such as epithelioid hemangioendothelioma and epithelioid angiosarcoma as the lesion can be successfully treated with curettage or resection.

Lepromatous leprosy in a case of epidermodysplasia verruciformis - A coincidence or a result of defective cell-mediated immunity?

Epidermodysplasia verruciformis (EDV) is a rare, autosomal recessive, genetic disorder of immune dysregulation characterized by increased susceptibility to cutaneous human papilloma virus infections. It was first described by Lewandowsky and Lutz in 1922 as a form of epidermal nevus. Its association with skin cancers was proposed by Sullivan and Ellis in 1939. Initial lesions often occur in childhood and are of two types; lifelong eruptions of pityriasis versicolor like lesions and flat wart like papules. The latter is characterized by malignant transformation in 35%-50% of patients especially after 40-50 years of age. Bowen disease is the most common tumor followed by invasive squamous cell carcinoma, however, metastasis is rarely encountered.

Best practices of handling, processing, and interpretation of small intestinal biopsies for the diagnosis and management of celiac disease: A joint consensus of Indian association of pathologists and microbiologists and Indian society of gastroenterology.

The Indian Association of Pathologists and Microbiologists (IAPM) and Indian Society of Gastroenterology (ISG) decided to make a joint consensus recommendation for handling, processing, and interpretation of SI biopsies for the diagnosis and management of celiac disease (CD) recognizing the inhomogeneous practice of biopsy sampling, orientation, processing, and interpretation. A modified Delphi process was used to develop this consensus document containing a total of 42 statements and recommendations, which were generated by sharing the document draft, incorporating expert's opinion, followed by three cycles of electronic voting as well as a full-day face-to-face virtual ZOOM meeting and review of supporting literature. Of the 42 statements, 7 statements are on small intestinal (SI) biopsy in suspected patients of CD, site and the number of biopsies; 7 on handling, fixative, orientation, processing, and sectioning in pathology laboratories; 2 on histological orientation; 13 statements on histological interpretation and histological grading; 3 on the assessment of follow-up biopsies; 2 statements on gluten-free diet (GFD)-nonresponsive CD; 4 on challenges in the diagnosis of CD; 2 statements each on pathology reporting protocol and training and infrastructure in this area. The goal of this guideline document is to formulate a uniform protocol agreed upon both by the experienced pathologists and gastroenterologists to standardize the practice, improve the yield of small bowel biopsy interpretation, patients' compliance, overall management in CD, and generate unified data for patient care and research in the related field.

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

BACKGROUND: Histological assessment of dysplasia in Barrett's 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, ß-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, ß-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 ß-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.

Primary signet cell adenocarcinoma of bladder.

Primary signet cell cancer of the urinary bladder is a relatively rare entity. Since there is no mucinous epithelium in the bladder, It is proposed that the tumor arises from metaplastic urothelium. Two thirds of the tumours are mucin secreting, in most of which the site of the deposition is either extracellular or intracellular displacing the nucleus to a peripheral crescent, giving the cells a signet ring appearance. The tumours are most often infiltrative and diffusely involving the majority of the bladder akin to its name sake in stomach. It is essential to distinguish this carcinoma from gastrointestinal metastases as different therapeutic strategies are often necessary.

Pitfalls in interpretation of FDG PET/CT: Septic pulmonary emboli mimicking metastases in a case of gastric carcinoma.

Inflammatory lesions may sometimes show intense tracer uptake and mimic neoplastic lesions on (18) F-fluoro-deoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT). We report one such false positive case on FDG PET/CT, where septic pulmonary emboli (SPE) mimicked pulmonary metastases. A 45-year-old man with stomach cancer had an indwelling central venous catheter (CVC) in situ while on neoadjuvant chemotherapy. He underwent FDG PET/CT scan for response assessment and the images revealed multiple, intensely FDG avid, peripheral, lung nodules with feeding vessels, which were suspicious for pulmonary metastases. A day later, the patient developed fever with chills and his blood culture showed bacterial growth (Enterobacter cloacae). A provisional diagnosis of SPE from an infected CVC was made. Chemotherapy was withheld, CVC removed, and the catheter tip was sent for bacterial culture. Following a 4-week course of antibiotic treatment, the patient became afebrile. Culture from the CVC tip grew the same organism, as was seen earlier in the patient's blood culture, thus pin-pointing the source of infection in our case. Diagnosis of SPE was clinched when follow-up CT chest done after completion of antibiotic course showed complete resolution of the lung lesions.

Does Hepatocyte Paraffin 1 expression stand a role in determining the site origin of an adenocarcinoma from unknown gastrointestinal primary?

BACKGROUND: Hepatocyte Paraffin 1 (Hep Par 1) was being extensively used to recognize the hepatocellular carcinomas, until recognition of its expression in tumors without hepatocellular differentiation. AIMS AND OBJECTIVES: The aim of this study was to analyze if Hep Par 1 stain can serve as a specific marker of the small intestinal (SI) adenocarcinomas, versus other gastrointestinal tract (GIT) primary tumors. MATERIALS AND METHODS: In this retrospective cross-sectional study, normal GIT mucosa (n - 60), corresponding adenocarcinomas (n - 60) and nodal metastatic foci (n - 60) from the same patients, including 10 cases each from the esophagus, stomach, SI periampullary region, colon, rectum, and gall bladder were included. H-score was calculated by multiplying the stain distribution and intensity scores. The H-scores were compared with other clinical and histological parameters. RESULTS: While normal SI mucosa showed diffuse strong Hep Par 1 staining, normal esophageal and gastric epitheliums were negative and normal colon, rectal, and biliary epithelium showed weak focal positivity. Adenocarcinomas from all these sites, however, showed Hep Par 1 expression, irrespective of the tumor type, site or origin, and tumor stage. The corresponding metastatic sites also showed variable Hep Par 1 positivity, without any site specificity. CONCLUSION: Hep Par 1 stain cannot help to determine the exact site of origin of primary GIT tumors. Its expression in adenocarcinomas across the GIT and their metastatic foci proves that it cannot be regarded as a marker of SI differentiation, especially in malignancy.

Large lipid-rich mammary analogue secretory carcinoma of parotid gland: An unusual case.

Mammary analogue secretory carcinoma (MASC) of the salivary gland is a malignant tumor which bears morphologic, immunohistochemical and molecular features similar to those of mammary secretory carcinoma. The tumor is considered as a low-grade malignancy perhaps slightly more aggressive than acinic cell carcinoma. High-grade transformation with recurrences, regional nodal involvement, metastases, and cancer-related death has been reported in a few cases. We report an unusual case of large MASC of the parotid gland in a young patient without regional lymph node involvement. To the best of our knowledge till date such a large MASC of the salivary gland has not been reported in the English literature.