Cutaneous T cell lymphomas represent a heterogenous group of lymphoproliferative disorders defined by clonal proliferation of T cells present in the skin. The latest WHO classification in 2016 and WHO-EORTC classification in 2018 has updated the classification of these entities based on the molecular profile. Research in the field of molecular genetics of CTCL has allowed a better understanding of the biology of these tumors and has helped to identify potential targets for therapy that can be tailored to individual patients. In this review, we discuss the latest developments in the molecular profile of CTCLs including biomarkers for diagnosis, prognosis, and potential therapeutic targets. We have also touched upon the utility of various molecular diagnostic modalities. For the purpose of this review, we researched papers in PubMed indexed journals in English literature published in the past 20 years using keywords CTCL, mycosis fungoides, molecular profile, molecular diagnosis, whole genome profile, genomic landscape, TCR clonality.

Objectives: Fine-needle aspiration cytology serves as a rapid and cost-effective tool for the diagnosis of melanoma, especially in the recurrent and metastatic cases. The diagnosis poses a challenge due to the varied morphological patterns. Spindle cell melanoma mimics other sarcomas and carcinomas on morphology. This study highlights the cytomorphological features of spindle cell melanoma and compares them with the conventional epithelioid type. Study Design: Cytology smears of 55 aspirates from 45 diagnosed cases of melanoma from various sites were reviewed. Histopathology correlation was done in spindle and mixed cell tumors. Results: Melanomas with a pure or mixed spindle cell component occurred in 31% of the cases and in a slightly higher age group. These demonstrated prominent cellular cohesion (p < 0.0001), mild to moderate nuclear atypia and inconspicuous to small nucleoli as compared to the epithelioid variant. The presence of melanin pigment was a useful clue to the diagnosis. Most of the cases correlated well with the histomorphology. Conclusion: Spindle cell melanoma is a morphological variant which can be readily misinterpreted due to a lack of classical cytological features of melanoma. Hence, these are vulnerable to be misinterpreted as other neoplasms. An awareness of clinical and cytological features is important to reach the correct diagnosis.

Background & objectives:Studies have shown that immunohistochemical (IHC) staining using epidermal growth factor receptor (EGFR) mutation specific antibodies, is an easy and cost-effective, screening method compared with molecular techniques. The purpose of present study was to assess the percentage positivity of IHC using EGFR mutation specific antibodies in lung biopsy samples from patients with primary lung adenocarcinoma (ADC).Methods:Two hundred and six biopsies of primary lung ADC were subjected to EGFR mutation specific antibodies against del E746-A750 and L858R. Detection of EGFR mutation done by high resolution melting analysis (HRM) was used as gold standard. A concordance was established between molecular and IHC results. Frequency of IHC positivity was assessed.Results:Of the 206 patients, 129 were male and 77 were female patients, with a mean age of 54.1 yr. Fifty five (26.6%) patients (36 men; 19 women) showed positivity for IHC of del E746-A750 (33) and L858R (22). HRM results were available in 14 patients which showed EGFR mutations in correspondence with del E746-750 or L858R in 64.2 per cent cases. Positive cases on HRM were further confirmed by DNA sequencing and fragment analysis. Three patients showed exon20 variation. Two cases were negative for mutation. The genotype of del E746-750 mutation was more common than L858R. A concordance was established between molecular mutation and IHC in 85.7 per cent cases.Interpretation & conclusions:In this preliminary study from India mutation specific IHC was used for assessment of mutation status of EGFR. Although the number tested was small, a good concordance was observed between molecular EGFR mutation and IHC expression. IHC methodology is a potentially useful tool to guide clinicians for personalized treatment in lung ADC, especially where facilities for molecular analysis are not readily available and for use in small biopsies where material is scant for molecular tests.

Background:Conventional transbronchial needle aspiration (c-TBNA) is an underutilized bronchoscopic modality. Endobronchial ultrasound (EBUS) guided-TBNA though efficacious is an expensive modality, facilities of which are available at only limited centers. c-TBNA is cost-effective and has potential for wide utilization especially in resource-limited settings. Rapid on-site evaluation (ROSE) improves the yield of c-TBNA.Materials and Methods:A retrospective review of the bronchoscopy records (May 2012 to July 2014) was performed. The patients who underwent c-TBNA with ROSE were included in the study and their clinical details were extracted. Convex probe EBUS-TBNA was being regularly performed during the study period by the operators performing c-TBNA.Results:c-TBNA with ROSE was performed in 41 patients with mean age of 42.4 (16.2) years. The most frequently sampled node stations (>90% patients) were the subcarinal and lower right paratracheal. Representative samples could be obtained in 33 out of the 41 patients (80.4%). c-TBNA was diagnostic in 32 [tuberculosis (TB)-8, sarcoidosis-9, and malignancy-15] patients out of the 41 patients. The overall diagnostic yield (sensitivity) of c-TBNA with ROSE was 78%. Mean procedure duration was 18.4 (3.1) min and there were no procedural complications.Conclusion:c-TBNA with ROSE is a safe, efficacious, and cost-effective bronchoscopic modality. When it was performed by operators routinely performing EBUS-TBNA, diagnostic yields similar to that of EBUS-TBNA can be obtained. Even at the centers where EBUS facilities are available, c-TBNA should be routinely performed.

Background & objectives:Accurate histopathological subtyping of non-small cell lung carcinoma (NSCLC) is essential for targeted therapeutic agents. Immunohistochemistry (IHC) is helpful in identification of different tumour subtypes. In this study two marker approaches, one each for glandular and squamous cell differentiation was applied to maximize the proportion of accurately subtyped NSCLC not otherwise specified (NOS) tumours on small biopsy samples.Methods:Two hundred and sixty three consecutive lung biopsies of primary lung carcinoma were prospectively studied. These were subtyped first morphologically and then by IHC for p40 and thyroid transcription factor-1 (TTF-1). The diagnosis of NSCLC-NOS before and after addition of IHC was evaluated. Results were correlated and validated with morphologically proven cases and matched surgical specimens.Results:Based on morphology, only 140 of the 263 (53.2%) cases of NSCLC were characterized, whereas 123 (46.7%) were classified as NSCLC-NOS type. With addition of IHC (p40 and TTF-1), the latter category reduced to 14.4 per cent and a sum of 225 (85.5%) cases were accurately subtyped into squamous cell carcinoma, adenocarcinoma and adenosquamous carcinoma. p40 showed 100 per cent sensitivity and specificity for squamous differentiation whereas TTF-1 showed sensitivity of 85.3 per cent and specificity of 98.1 per cent. Ninety per cent correlation of morphologic subtypes was achieved with matched resected specimens.Interpretation & conclusions:Our results showed that an approach of using only a two-antibody panel (p40 and TTF-1) might help in reduction of diagnostic category of NSCLC-NOS significantly and contribute in saving tissue for future molecular testing.