Clinicopathological Spectrum of Cutaneous Lymphomas and Distinction of Early Mycosis Fungoides from its Mimics-A Retro-Prospective Descriptive Study from Southern India.

Background: Cutaneous lymphomas (CLs) could be either primary (PCL) or secondary; the former comprises cutaneous T-cell lymphomas (CTCLs) and cutaneous B-cell lymphomas (CBCLs). Mycosis fungoides (MF) is the most common PCL. Diagnosis of early MF and distinguishing it from benign inflammatory mimics is challenging. This study aims to assess the clinicopathological spectrum of CL and to characterize early MF from its mimics using clinical characteristics, histopathological features, and ancillary techniques. Materials and Methods: This retro-prospective descriptive study was conducted in a tertiary-care institute, for over 5 years. Clinically as well as histopathologically suspected and biopsy-proven CL and their mimics were included. Cases were reviewed and subgrouped based on clinical and histopathological parameters and immunohistochemistry (IHC). Data were analyzed using descriptive statistics and a Chi-square test at a 5% level of significance. Results: Among PCL, CTCL comprised 84% (21/25) and CBCL was 16% (4/25); the most common CTCL was MF at 81% (17/21). Histologically, atypia of dermal infiltrate (100%), epidermotropism (91.7%), basal alignment of lymphocytes (91.7%), clear haloed cells (91.7%), wiry collagen (66.7%), grandiosity sign (50%), eccrine infiltration (66.7%), and follicular infiltration (50%) were significantly associated with early MF. Spongiosis (84.6%), pigment incontinence (84.6%), exocytosis (76.9%), and parakeratosis (76.9%) were significantly associated with inflammatory mimics. There was no significant difference in the downregulation pattern of CD7 (P = 0.206) between early MF and its mimics. The four cases of CBCL in our study were plasmablastic lymphoma, diffuse large B-cell lymphoma, follicular lymphoma, and lymphoblastic lymphoma. Conclusion: MF was the most common PCL. Histological parameters showed a significant difference, whereas IHC did not show any significant difference between early MF and its mimics.

Association Analysis of Tumor Necrosis Factor Alpha Promoter Polymorphisms and Vitiligo Susceptibility in South Indian Tamils.

Tumor necrosis factor alpha (TNF-α) has been associated with the pathogenesis of several autoimmune diseases. Also, various studies in different ethnics showed an association between TNF-α gene polymorphisms and susceptibility to vitiligo. The paucity of genetic data led us to undertake this study to evaluate the association of five TNF-α SNPs (rs1799964, rs1800630, rs1799724, rs1800629, and rs361525) with the development of vitiligo in South Indian Tamils. A total of 264 vitiligo patients and 264 healthy controls were recruited and TNF-α genotyping was performed using amplification-refractory mutation system polymerase chain reaction and TaqMan allele discrimination assay. Circulatory TNF-α levels were measured by enzyme-linked immunosorbent assay. We observed that a single polymorphic allele A in the promoter region -308 (rs1800629) conferred significant risk to develop vitiligo (p = 0.0002, OR = 1.70, 95% CI = 1.28-2.25), whereas the other polymorphisms failed to contribute to disease risk (p > 0.05). From the constructed haplotypes, TCCAG was found to be a significant risk factor for vitiligo (p < 0.05). Also, a strong linkage disequilibrium was observed between the following SNPs: (1) rs1799964 and rs1800629 (2) rs1800630 and rs1799724 (D' = 0.90). Analysis of the influence of genotype on phenotypes revealed that the A allele of rs361525 was a risk factor for vitiligo in females (p = 0.04, OR = 0.45, 95% CI = 0.21-0.95), whilst the rs1800629 allele conferred protection against early disease onset (p < 0.05). A statistically significant difference in plasma TNF-α levels was found between cases and controls (p < 0.05). The TNF-α -308A allele and TCCAG haplotype were identified as genetic risk factors for vitiligo susceptibility in South Indian Tamils.

Subcutaneous Panniculitis-Like T Cell Lymphoma: Approach to Differential Diagnosis on Cytology.

Sighting a case of subcutaneous panniculitis-like T cell lymphoma (SPTCL) in cytology is very rare in a clinical scenario. Among the differential diagnoses (D/D) of a subcutaneous nodule undergoing fine needle aspiration cytology (FNAC), it is hardly considered in the list. The common D/D on cytology would be panniculitis or a non-SPTCL lymphoma. To make a correct cytological diagnosis, the pathologist has to meticulously observe the type of inflammatory infiltrate, their morphology, the intimate admixture of the fat lobules, and background necrosis or macrophages. This article describes the cytological picture, D/D, and the prognostic factors associated with SPTCL in a young male. He was suspected of SPTCL after FNAC and later confirmed on histopathology with specific immunomarkers. We do not recommend the confirmation of SPTCL on cytology however, we would like to stress that it can be picked up and differentiated from its mimickers on FNAC.

Incontinentia pigmenti, an x-linked dominant disorder, in a 2-year-old boy with Klinefelter syndrome.

Incontinentia pigmenti (IP) is a rare X-linked dominant disorder, in which skin lesions distributed along Blaschko's lines appear shortly after birth. Early lesions which are erythematous/bullous evolve over time into warty lesions, hyperpigmented swirls/macules, and atrophic hypopigmented streaks. Clinical features are heterogeneous. Abnormalities of the teeth, nails, hair, eyes, central nervous system, and breast may also be present. While intelligence is generally normal, varied degrees of intellectual disability/developmental delay have been reported. Lifespan is normal. IP is associated with mutations of the inhibitor of kappa light polypeptide gene enhancer in B cell, kinase gamma (IKBKG) gene on chromosome Xq28. This gene is involved in the activation of nuclear factor kappa B which protects cells against apoptosis; therefore, cells with IKBKG mutations are extremely susceptible to apoptosis. X-linked dominant disorders are lethal to male fetuses. Males who survive with IP either have mosaicism or an additional X chromosome (Klinefelter syndrome). We present a 22-month-old boy with IP and Klinefelter syndrome.

Vascular endothelial growth factor (VEGF) gene polymorphisms (rs699947, rs833061, and rs2010963) and psoriatic risk in South Indian Tamils.

BACKGROUND: Psoriasis is a chronic inflammatory disease of the skin. Vascular endothelial growth factor (VEGF), a pro-angiogenic factor, is involved in the pathogenesis of psoriasis. Being highly polymorphic, several SNPs of VEGF have been reported to be associated with increased risk of psoriasis. OBJECTIVES: We determined the association of VEGF gene polymorphisms with risk of psoriasis in South Indian Tamils. METHODS: 300 cases of psoriasis and 300 controls were recruited in this case-control study. Genotyping of SNPs of VEGF gene was done using Taqman 5' allele discrimination assay. Estimation of VEGF levels in plasma was done by ELISA. RESULTS: VEGF (rs2010963) polymorphism and the CTC haplotype were found to confer an increased risk of psoriasis. However, two other VEGF SNPs, rs833061, and rs699947, showed no association with psoriasis susceptibility. VEGF levels were higher in patients with psoriasis, as compared with controls and significantly correlated with disease severity. CONCLUSIONS: Our results indicate that VEGF (rs2010963) polymorphism and CTC haplotype of the VEGF SNPs (rs699947, rs833061, and rs2010963) confer an increased risk of psoriasis in the South Indian Tamil population. Plasma VEGF levels are higher in patients with psoriasis, as compared with controls and are significantly correlated with disease severity.

Familial gastrointestinal stromal tumors, lentigines, and café-au-lait macules associated with germline c-kit mutation treated with imatinib.

BACKGROUND: Familial lentiginosis syndromes are characterized by a wide array of manifestations resulting from activation of molecular pathways which control growth, proliferation, and differentiation of a broad range of tissues. Familial gastrointestinal stromal tumors (GISTs) are often accompanied by additional features like hyperpigmentation, mastocytosis, and dysphagia. They have been described with mutations in c-kit (most commonly), platelet-derived growth factor receptor A, neurofibromatosis-1, and succinate dehydrogenase genes. MATERIALS AND METHODS: We report on molecular characterization and tumor histopathology of two siblings in whom lentigines and café-au-lait macules were present along with multifocal GIST. Immuhistochemical analysis of CD34 and CD117 was performed on GIST biopsy samples from both siblings, while c-kit mutational analysis was done by PCR and direct sequencing on DNA from peripheral blood leukocytes of all family members and from paraffin-embedded gastric biopsy specimens of affected siblings. RESULTS: Histopathology revealed positive expression of CD117 and CD34. Mutational analysis showed the germline c.1676T>C mutation in c-kit exon 11, (p.(Val559Ala)), in the peripheral blood of both siblings and a second exon 11 mutation, c.1669T>A (p.(Trp557Arg)) in the tumor biopsy of one of them. Initiation of imatinib treatment resulted in striking resolution of their hyperpigmentation and a stable gastrointestinal disease in one of them. CONCLUSIONS: A c-kit mutational test in familial GISTs is indicated before initiation of imatinib therapy, as it can help predict tumor response to treatment.

Disseminated Kaposi's Sarcoma in an HIV-Positive Patient: A Rare Entity in an Indian Patient.

AIDS-associated disseminated Kaposi sarcoma (KS) is a rare entity, especially in India due to the low prevalence of human herpes virus-8 infections in Indian population. Due to its rapid and progressive nature, early diagnosis and institution of highly active antiretroviral therapy is crucial in AIDS-associated KS, with a view to achieving favorable prognosis. We report a case of disseminated KS in an HIV-1 positive patient, who presented with two months history of multiple violaceous patches and plaques over the trunk, bilateral upper limbs, lower limbs, and hard palate. The patient died of recurrent massive pleural effusion before starting antiretroviral therapy. This case is being reported due to the paucity of KS in the Indian literature, especially the disseminated type and to highlight its rapidly progressive course which can be fatal.

Serotonin and interleukin-6: Association with pruritus severity, sleep quality and depression severity in Prurigo Nodularis.

Prurigo Nodularis (PN) is a chronic skin condition of unknown etiology. It is said to be associated with psychological factors. However, studies to identify the same are few. Hence, we undertook to assess the association between quality of sleep, depression, pruritus severity in cases of PN and to assess association of serum serotonin, interleukin (IL)-6 with sleep, depression and pruritus severity. This cross-sectional study involves 39 patients with PN and 39 age and gender matched healthy controls. Subjective quality of sleep, depressive symptom severity and pruritus severity were collected through clinician based interview. Serum serotonin and serum IL-6 were estimated by ELISA. Spearman correlation was used to assess the strength of association between biochemical parameters and clinical parameters. Cases had significantly higher percentage of depression, a higher score of depression severity, higher serum IL-6 level and lower serum serotonin levels. Serum serotonin and serum IL-6 showed significant correlation with the severity of pruritus (r=-0.66, p<0.01 and r=0.60, p<0.01). However, both these parameters showed a significantly negative correlation between them (r=-0.92, p<0.01). Though cause and effect cannot be established in this type of study, there is a disturbance of the inflammatory-neuroendocrine axis (interleukins-serotonin). PN is characterized by higher IL-6 and lower serotonin and greater depression severity than healthy controls. Findings of this study may have an influence on the treatment of PN.

Reactive Eccrine Syringofibroadenomatosis Presenting as Bilateral Plantar Hyperkeratosis.

Eccrine syringofibroadenoma (ESFA) is a rare cutaneous tumor with eccrine differentiation with varied clinical manifestations. We report a case of reactive eccrine syringofibroadenomatosis associated with chronic bilateral plantar ulcers in a patient with diabetes mellitus presenting as plantar hyperkeratosis and verrucous growth at margins.