Bullous pemphigoid in India: Review of cases registered in an autoimmune bullous disease clinic

Background: Information on bullous pemphigoid in an Indian context is scarce. Aim: To report clinico-demographic profile, associated comorbidities and prescription pattern of bullous pemphigoid patients in India. Methods: This was a retrospective study, where past records of all bullous pemphigoid patients diagnosed and treated between November 2013 and October 2019 were accessed and analysed. Patients having a compatible clinical presentation with either histopathological and/or direct immunofluorescence evidence of bullous pemphigoid were included. Results: There were 96 bullous pemphigoid patients, with a male: female ratio of 1.6:1. The mean age at diagnosis was 62.5 ± 2.2 years, with mean duration of illness 27.5 ± 4.5 months before presentation. Comorbidities were present in 80 (83%) patients, with type 2 diabetes mellitus (38.5%), hypertension (36.4%) and neurological illness (16.7%) being the commonest ones. Clinically, blisters were the predominant presentation in 81 (84.4%) patients. The majority (87.5%) of patients showed a predominant eosinophilic infiltrate on histopathology. Direct immunofluorescence revealed immunoglobulin G deposits with complement C3 in 77 (80.2%) cases. The majority of patients (77.1%) were treated with oral prednisolone, either alone (11.5%) or in combination (65.6%) with other topical and systemic agents. Topical steroids were used in 29.1%, azathioprine in 28%, dapsone in 16.7% and omalizumab in 6.2% of patients. Limitations: The study is retrospective. Immunofluorescence on salt split skin, direct immunofluorescence serration pattern analysis, and immunoblotting were not performed. Hence, there is a possibility that a few included cases were suffering from other subepidermal autoimmune bullous diseases like epidermolysis bullosa acquisita or anti-p200 pemphigoid. Conclusion: Bullous pemphigoid patients in this study had a younger age of onset and showed male preponderance. Comorbidities like type 2 diabetes, hypertension and neurological disorders were freq

Contiguous squamous proliferations in syringocystadenoma papilliferum: A retrospective study of 14 cases

Background: Syringocystadenoma papilliferum is a benign adnexal neoplasm. Contiguous squamous proliferation has been rarely described in syringocystadenoma papilliferum. Aims: This study aimed to evaluate the spectrum and pathogenesis of contiguous squamous proliferation in syringocystadenoma papilliferum. Materials and Methods: All cases of syringocystadenoma papilliferum diagnosed over the past 12 years were screened for contiguous squamous proliferation. Cases with associated nevus sebaceous were excluded from the study. Immunohistochemistry for GATA3, CK7, BRAFV600E and p16 was performed. PCR for human papilloma virus, type 16 and 18, was carried out. Results: Of a total of 30 cases, 14 cases showed associated contiguous squamous proliferation which included four cases of verrucous hyperplasia, six cases with papillomatosis, two cases with mild squamous hyperplasia and one case each of Bowen’s disease and squamous cell carcinoma. In the cases with non-neoplastic contiguous squamous proliferations, the squamous component did not express CK7 or GATA3. However, the squamous component of premalignant and malignant lesions expressed CK7 and GATA3 concordant with the adenomatous component. BRAF was positive in adenomatous component in five cases while the contiguous squamous proliferation component was negative for BRAF in all but one case. p16 was negative in both components of all cases and PCR for human papilloma virus was negative in all cases. Limitations: Due to the rarity of disease, the sample size of our study was relatively small with two cases in the 2nd group, that is, syringocystadenoma papilliferum with malignant contiguous squamous proliferation. Detailed molecular studies such as gene sequencing were not performed. Conclusion: Syringocystadenoma papilliferum with contiguous squamous proliferation is underreported, and most commonly displays verrucous hyperplasia. The premalignant and malignant contiguous squamous proliferations likely arise from syringocystadenoma papilliferum while the hyperplastic contiguous squamous proliferations likely arise from the adjacent epidermis. Relationship with high-risk human papilloma virus is unlikely. However, further molecular analysis of larger number of cases is required to establish the pathogenesis.

Primary diffuse large B-cell lymphoma of the CNS, with a "Lymphomatosis cerebri" pattern

We describe an unusual case of lymphomatosis cerebri in a middle-aged lady presenting with rapid-onset dementia. The lymphomatous infiltrate, instead of forming mass lesions, percolated throughout the brain parenchyma, which is often missed on a stereotactic biopsy and hence warrants caution and awareness about this entity. The nonspecific symptoms at presentation and a variable picture at imaging make this entity diagnostically challenging.

Clinical, demographic and immunopathological spectrum of subepidermal autoimmune bullous diseases at a tertiary center: A 1-year audit.

Background: The subepidermal autoimmune bullous diseases are a subset of immunobullous diseases encountered less frequently in the Indian population. There is a paucity of data on the prevalence, demographic and clinicopathological spectrum of various subepidermal autoimmune bullous diseases from India. Aim: To determine the demographic and clinicopathological profi le of subepidermal autoimmune bullous diseases in Indian patients, presenting to the Immunobullous Disease Clinic of Postgraduate Institute of Medical Education and Research, Chandigarh. Methods: Patients seen from November 2013 to November 2014 who fulfi lled the preset diagnostic criteria of subepidermal autoimmune bullous diseases were identifi ed from case records. Data regarding demographic characteristics, clinical profi le, immunopathological fi ndings and treatment were collected from the predesigned proforma. Results: Of 268 cases of autoimmune bullous diseases registered, 50 (18.7%) were subepidermal autoimmune bullous diseases. Bullous pemphigoid was most frequently seen in 20 (40%) cases, followed by dermatitis herpetiformis in 14 (28%), mucous membrane pemphigoid in 6 (12%), chronic bullous dermatosis of childhood / linear immunoglobulin A bullous dermatosis in 5 (10%), lichen planus pemphigoides in 3 (6%), pemphigoid gestationis and epidermolysis bullosa acquisita in 1 (2%) case each. None of the patients had bullous systemic lupus erythematosus. Limitations: We could not perform direct and indirect immunofl uorescence using salt-split skin as a substrate and immunoblotting due to non-availability of these facilities. Therefore, misclassifi cation of subepidermal autoimmune bullous diseases in some cases cannot be confi dently excluded. Conclusion: Subepidermal autoimmune bullous diseases are not uncommon in Indian patients. Bullous pemphigoid contributes maximally to the burden of subepidermal autoimmune bullous diseases in India, similar to that in the West, although the proportion is lower and disease onset is earlier. Dermatitis herpetiformis was observed to have a higher prevalence in our population, compared to that in the West and the Far East countries. The prevalence of other subepidermal autoimmune bullous diseases is relatively low. Detailed immunofl uorescence and immunoblotting studies on larger patient numbers would help better characterize the pattern of subepidermal autoimmune bullous diseases and their features in Indian patients.

Predisposing factors and histopathological variants of cutaneous squamous cell carcinoma: Experience from a North Indian teaching hospital.

Background: Squamous and basal cell carcinomas together constitute the majority of non-melanoma skin cancers. These malignancies are infrequent in Indians as compared to the white skinned population. Literature on squamous cell carcinoma in dark skin is limited. Aim: To analyze the risk factors and to characterize the histopathological subtypes of cutaneous squamous cell carcinoma in Indian patients in an area, non-endemic for arsenicosis. Methods: A retrospective analysis of data from January 2003 to August 2013 was performed to evaluate the predisposing factors and histopathological types of cutaneous squamous cell carcinoma at the Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh. Demographic and disease characteristics such as age, gender and predisposing factors, particularly premalignant dermatoses were recorded and histopathology slides were reviewed. Results: Of the 13,426 skin biopsy specimens received during the 10-year period, there were 82 (0.6%) cases of squamous cell carcinoma and 170 (1.7%) of basal cell carcinoma. The mean age at diagnosis of cutaneous squamous cell carcinoma was 53.7 years and the male to female ratio was 2:1. The most common site of involvement was the lower limbs in 34 (41.5%) patients. Marjolin’s ulcer was present in 36 (43.9%) cases. No predisposing factor was identifi ed in 35 (42.7%) patients. Histopathologically, the tumors were classifi ed most commonly as squamous cell carcinoma not otherwise specifi ed in 33 (40.2%) cases. Limitations: This was a retrospective study and details of occupation and interval between the precursor lesions and development of tumor were not recorded. Immunohistochemistry for human papilloma virus and p53 tumor suppressor protein were not performed as these tests were not available. Conclusion: Cutaneous squamous cell carcinoma is uncommon in Indian patients and a high index of suspicion is necessary when a rapidly enlarging nodule, verrucous fungating plaque or an ulcer with everted margins develops in long standing scars and other predisposing dermatologic conditions. Histopathological examination is mandatory to confi rm the diagnosis and identify the subtype and this has prognostic implications.

Role of dental restoration materials in oral mucosal lichenoid lesions.

Background: Dental restorative materials containing silver–mercury compounds have been known to induce oral lichenoid lesions. Objectives: To determine the frequency of contact allergy to dental restoration materials in patients with oral lichenoid lesions and to study the effect of removal of the materials on the lesions. Results: Forty‑five patients were recruited in three groups of 15 each: Group A (lesions in close contact with dental materials), Group B (lesions extending 1 cm beyond the area of contact) and Group C (no topographic relationship). Thirty controls were recruited in two groups of 15 individuals each: Group D (oral lichenoid lesions but no dental material) and Group E (dental material but no oral lichenoid lesions). Patch tests were positive in 20 (44.5%) patients. Mercury was the most common allergen to elicit a positive reaction in eight patients, followed by nickel (7), palladium (5), potassium dichromate (3), balsam of Peru, gold sodium thiosulphate 2 and tinuvin (2) and eugenol (1), cobalt chloride (1) and carvone (1). Seven patients elicited positive response to more than one allergen. In 13 of 20 patients who consented to removal of the dental material, complete healing was observed in 6 (30%), marked improvement in 7 (35%) and no improvement in 7 (35%) patients. Relief of symptoms was usually observed 3 months after removal. Limitations: Limited number of study subjects and short follow up after removal/replacement of dental restoration materials are the main limitations of this study. Conclusion: Contact allergy to amalgam is an important etiologic factor in oral lichenoid lesions and removal of restorative material should be offered to patients who have lesions in close proximity to the dental material.

Invasive micropapillary carcinoma of urinary bladder: A clinicopathological study.

Context: Micropapillary variant of urothelial carcinoma (MPUC) is a rare but well-recognized tumor of the urinary bladder. Tumors with micropapillary areas accompanying conventional urothelial carcinoma are more aggressive compared to conventional urothelial carcinoma and show variable keratin 7, keratin 20 and human epidermal growth factor receptor 2 (Her 2)neu expression. Aim: The aim of the study was to analyze the clinical, morphological and immunohistochemical profi le of MPUC. Materials and Methods: Transurethral resection of bladder tumor (TURBT) chips of seven cases of invasive MPUC with subsequent cystoprostatectomy specimens of five patients was reviewed. Epithelial membrane antigen (EMA), Keratin 7, Keratin 20, and Her 2 immunohistochemistry were performed in all cases. Follow-up information was available for all patients (2-36 months). Results: All seven patients were male, and their ages ranged from 50 to 62 years. All cases presented with hematuria. The micropapillary pattern was seen in 20-95% of the tumor. All cases showed extensive lymphatic emboli with detrusor muscle invasion. Lymph node metastasis was present in all cases undergoing cystoprostatectomy except one. Keratin 7 and abluminal pattern of EMA positivity were seen in all cases. Keratin 20 was positive in fi ve cases (71%), and Her 2neu positivity was seen in four cases. Three patients died 2, 3, and 6 months after initial diagnosis, among which two were Her 2 positive and one was Her 2 negative. There was no clear prognostic signifi cance of Her 2 positivity. Conclusion: (1) MPUC is a rare but highly aggressive tumor. (2) Micropapillary is usually the predominant pattern. (3) Keratin 7 is expressed universally, whereas Keratin 20 expression is variable. (4) Her 2 expression has no clear infl uence on the survival

Secretory meningioma: A diagnostic pitfall.

Context: Secretory meningioma is a rare subtype of meningiomas, displaying epithelial and secretory differentiation of meningothelial cells. It has unique radiological, morphological, and immunohistochemical features, but runs a benign course. Radiological picture because of the variable degrees of peritumoral edema can be confused with aggressive neoplasms. Morphologically, it is diffi cult to distinguish secretory meningioma from other tumors having a clear cell appearance and aggressive clinical behavior. Materials and Methods: Retrospective analysis over a period of 16 years (1997-2012) brought out fi ve cases diagnosed as secretory meningioma. The slides were restained and subject to special stains and immunohistochemistry and the clinical details were retrieved. Results: On histopathology, the tumors showed a characteristic vacuolated appearance due to the presence of variably sized intracytoplasmic lumina. Another unique feature was the presence of hyaline inclusions within these intracytoplasmic lumina and in the intercellular spaces. These inclusions were periodic acid-Schiff positive diastase-resistant, yellowish-orange on Elastic Van Giesson stain and strongly carcinoembryonic antigen positive. Conclusion: Owing to its rarity and unique morphology secretory meningioma poses a diagnostic challenge to the pathologists. As this tumor follows a benign course, it is crucial to correctly diagnose this entity to avoid unnecessary over treatment.

Cutaneous vasculitides: Clinico-pathological correlation.

Background: Cutaneous vasculitis presents as a mosaic of clinical and histological findings. Its pathogenic mechanisms and clinical manifestations are varied. Aims: To study the epidemiological spectrum of cutaneous vasculitides as seen in a dermatologic clinic and to determine the clinico-pathological correlation. Methods: A cohort study was conducted on 50 consecutive patients clinically diagnosed as cutaneous vasculitis in the dermatology outdoor; irrespective of age, sex and duration of the disease. Based on the clinical presentation, vasculitis was classified according to modified Gilliam's classification. All patients were subjected to a baseline workup consisting of complete hemogram, serum-creatinine levels, serum-urea, liver function tests, chest X-ray, urine (routine and microscopic) examination besides antistreptolysin O titer, Mantoux test, cryoglobulin levels, antineutrophilic cytoplasmic antibodies and hepatitis B and C. Histopathological examination was done in all patients while immunofluorescence was done in 23 patients. Results: Out of a total of 50 patients diagnosed clinically as cutaneous vasculitis, 41 were classified as leukocytoclastic vasculitis, 2 as Heinoch−Schonlein purpura, 2 as urticarial vasculitis and one each as nodular vasculitis, polyarteritis nodosa and pityriasis lichenoid et varioliforme acuta. Approximately 50% of the patients had a significant drug history, 10% were attributed to infection and 10% had positive collagen workup without any overt manifestations, while 2% each had Wegener granulomatosis and cryoglobulinemia. No cause was found in 26% cases. Histopathology showed features of vasculitis in 42 patients. Only 23 patients could undergo direct immunofluorescence (DIF), out of which 17 (73.9%) were positive for vasculitis. Conclusions: Leukocytoclastic vasculitis was the commonest type of vaculitis presenting to the dermatology outpatient department. The workup of patients with cutaneous vasculitis includes detailed history, clinical examination and investigations to rule out multisystem involvement followed by skin biopsy and DIF at appropriate stage of evolution of lesions. Follow up of these patients is very essential as cutaneous manifestations may be the forme fruste of serious systemic involvement.

Cytology of Hürthle cell neoplasms of thyroid gland.

Hürthle cell neoplasms (HCN) are an uncommon group of tumors of the thyroid gland. Fine needle aspiration cytology (FNAC) is an important diagnostic tool in solitary nodules of the thyroid gland. A 5-year retrospective analysis of all cases diagnosed as HCN on cytology was performed and correlated with the corresponding histopathology wherever available. There were 13 cases diagnosed as HCN out of which 6 cases had subsequent histopathologic examination. Four were adenomas and two were carcinomas. In addition, 3 cases that were adenomas on histopathology were reported on cytology as colloid goiter with cystic degeneration in 2 cases and as follicular adenoma in 1 case. There was extensive cystic degeneration in the former two cases whereas poor cellular preservation led to misdiagnosis in the third case. There were no specific cytomorphological features that distinguished adenoma from carcinoma. FNAC has a high specificity for a diagnosis of HCN, but the sensitivity is not as high because of sampling error.

Does c-erbB-2 expression have a role in medulloblastoma prognosis?

The prognosis of patients with medulloblastoma has remained same for the last two decades. This study evaluated the role of c-erbB-2 expression in medulloblastoma as a prognostic marker. Fifty cases of medulloblastomas were investigated for the expression of c-erbB-2 protein using immunohistochemistry. The expression of c-erbB-2 was correlated with age, histology and disease-free survival (DFS). Thirty-five (70%) tumors were c-erbB-2 positive. Immunoreactivity for c-erbB-2 receptor was observed as mixed cytoplasmic and membrane positivity of tumour cells. The mean DFS in c-erbB-2 positive cases was 19.81 months compared to 48.33 months in c-erbB-2 negative cases. c-erbB-2 positivity was found to be an independent predictor of poor outcome in medulloblastoma (p value < 0.05). No correlation of c-erbB-2 expression was observed with the age of patient and the histological type of tumour. Additionally, c-erbB-4 expression was also evaluated in these tumours. Thirty-three cases showed co-expression of c-erbB-2 and c-erbB-4 proteins. However, c-erbB-4 expression alone was not associated with poor outcome, whereas its co-expression with c-erbB-2 was associated with shorter DFS (p < 0.05).

Plasmacytoma of the clivus: a case report.

A 60-year-old male presented with headache and diplopia for 2 months. Computed tomography of the head showed a heterogeneously enhancing expansile lytic lesion in clival region. The patient underwent surgery and histopathological examination revealed it to be plasmacytoma of the clivus. The multiple myeloma work-up was negative. Solitary plasmacytoma localized to the skull base is extremely rare. Prior to this, only three case reports of plasmacytoma of the clivus have been described in the English literature.

Giant calvarial hyperostosis with biparasagittal en plaque meningioma.

We report a patient with an uncommon presentation in the form of massive bilateral calvarial hyperostosis with bi-parasagittal en plaque meningioma. The tumour was removed by bilateral fronto-parieto-occipital craniotomies. The patient was subjected to post operative radiotherapy to reduce the chances of recurrance. The management of such a case is a surgical challenge.

Histopatholgical spectrum of thymic neoplasms: twelve-year experience at a referral hospital in north India.

This study was undertaken to determine the histopathological spectrum and clinical profile of thymic neoplasms at a tertiary referral care centre. A total of 96 thymectomy specimens were received during the study period (1992-2004), which consisted of 54 neoplasms and 42 benign lesions. Among the neoplasms there were 48 thymic epithelial tumors, 3 thymolipomas and 3 thymic carcinoids. The former comprised of 36 male (75%) and 12 female patients (25%) ranging in age from 2-70 years (mean 37 years). Among paraneoplastic syndromes in thymic epithelial tumours, 27 out of 48 (56.25%) cases were associated with myasthenia gravis and one case was associated with pure red cell aplasia. The most frequent histological subtype was cortical thymoma (43.24%) followed by predominantly cortical (24.32%) and well-differentiated thymic carcinoma (18.92%). On staging, all cases of mixed and predominantly cortical subtype were stage 1 whereas one medullary and 2 cortical thymomas and 4 well differentiated thymic carcinoma (WDTC) showed pleural and pericardial invasion (stage III). This study has revealed that half of thymic epithelial tumours presented as myasthenia gravis. The cortical thymoma was the most frequently encountered histologic subtype and most commonly associated with myasthenia gravis.

Partial duplication of head--a rare congenital anomaly.

Duplication of notochord results in rare congenital anomalies like double headed monsters, with or without trunk/limb duplication, depending upon the extent of notochordal abnormality. Here we describe the morphological abnormalities in a case of partial duplication of cranial structures with fusion of the two. Autopsy findings suggest that the bifurcation of the neural tube took place around 4th to 6th week of gestation. There are only few reports in English literature describing the autopsy findings of such an anomaly, which is termed as Diprosopus triophthalmus in the modern literature.

Pathological spectrum of cytomegalovirus infection of renal allograft recipients-an autopsy study from north India.

This is a retrospective study of autopsy material to highlight the histo-morphological changes in cytomegalovirus (CMV) infection amongst renal allograft recipients. Nineteen out of 80 patients (23.75%) autopsied during a seventeen-year period (1985-2001) had CMV infection. Pulmonary infection was present in 14 out of 19 cases of which four had isolated lung involvement. Likewise, there were two cases each of isolated oesophageal and renal involvement; one case with isolated colonic involvement. The other 10 cases had multi-organ involvement and the organs involved were kidneys (4), esophagus (6), stomach (1), colon (5), adrenals (3), pancreas (3), liver (1) and spleen (1). Pulmonary infection with CMV was associated with acute pneumonitis in 3 cases and lymphocytic interstitial pneumonitis in 9 instances. Four out of 6 cases had acute tubulo-interstitial nephritis induced by CMV and only two cases had no significant inflammatory response. Glomerular involvement in the form of CMV inclusions in the glomeruli was present in only one case. Gastrointestinal CMV infection (15) presented as acute necrotizing ulceration because of predominant endothelial involvement. Post transplant survival period varied from one month to three years, with majority (14) of the patients having survived for less than one year.