SUMMARY We describe the landscape of genomic alterations in cutaneous melanomas through DNA, RNA, and protein-based analysis of 333 primary and/or metastatic melanomas from 331 patients. We establish a framework for genomic classification into one of four subtypes based on the pattern of the most prevalent significantly mutated genes: mutant BRAF, mutant RAS, mutant NF1, and Triple-WT (wild-type). Integrative analysis reveals enrichment of KIT mutations and focal amplifications and complex structural rearrangements as a feature of the Triple-WT subtype. We found no significant outcome correlation with genomic classification, but samples assigned a transcriptomic subclass enriched for immune gene expression associated with lymphocyte infiltrate on pathology review and high LCK protein expression, a T cell marker, were associated with improved patient survival. This clinicopathological and multidimensional analysis suggests that the prognosis of melanoma patients with regional metastases is influenced by tumor stroma immunobiology, offering insights to further personalize therapeutic decision-making.

EGFR mutation testing should be attempted in any specimen, whether histologic or cytologic. Samples should not be excluded from testing based on TTF-1 status or histologic features. Pathologists should report the amount of available tumor for testing. However, suboptimal samples with a negative EGFR mutation result should be considered for repeat testing with an alternate sample.

No abstract

Benign spindle cell lesions of the breast include neoplastic and reactive entities that are diagnostically challenging given their rarity and similar histomorphology. Accurate diagnosis on percutaneous core biopsy within this category is essential as some lesions require excision and surveillance, whereas others may be observed. We present three cases of rare benign spindle cell lesions of the breast that reflect the diversity of this group: solitary fibrous tumour, nodular pseudoangiomatous stromal hyperplasia and nodular fasciitis. Through these cases, we discuss the associated differential diagnosis and demonstrate how emerging ancillary studies can be integrated into a diagnostic approach. We highlight distinctive clinical and histopathological features and summarise recent updates to the clinical management of these lesions. An organised approach to the broad differential of spindle cell lesions is essential for appropriate diagnosis and treatment.

The diagnosis of panniculitis is a relatively rare occurrence for many practising pathologists. The smaller subset of lymphocyte-predominant panniculitis is further complicated by the diagnostic consideration of T cell lymphoma involving the subcutaneous tissue, mimicking inflammatory causes of panniculitis. Accurate classification of the panniculitis is crucial to direct clinical management as treatment options may vary from non-medical therapy to immunosuppressive agents to aggressive chemotherapy. Many diseases show significant overlap in clinical and histological features, making the process of determining a specific diagnosis very challenging. However, with an adequate biopsy including skin and deep subcutaneous tissue, a collaborative effort between clinician and pathologist can often lead to a specific diagnosis. This review provides an algorithmic approach to the diagnosis of lymphocyte-predominant panniculitis, including entities of septal-predominant pattern panniculitis (erythema nodosum, deep necrobiosis lipoidica, morphea profunda and sclerosing panniculitis) and lobular-predominant pattern panniculitis (lupus erythematous panniculitis/lupus profundus, subcutaneous panniculitis-like T cell lymphoma, cutaneous γ-δ T cell lymphoma, Borrelia infection and cold panniculitis).

Background:We examined clinical outcomes in a population-based cohort of EGFR mutant advanced NSCLC patients, exploring the potential role of factors including tumour EGFR mutation fraction and cellularity in predicting outcomes.Methods:A cohort of patients with EGFR mutant advanced NSCLC was identified (N=293); clinical outcomes, pathologic and treatment details were collected. Tumour response was determined from radiology and clinical notes. Association between demographic and pathologic variables EGFR TKI response, time to treatment failure (TTF) and overall survival (OS) was examined using logistic regression and proportional hazards regression. EGFR TKI response rates were summarised by percent mutation fraction to explore their association.Results:Higher mutation fraction was associated with greater EGFR TKI response rate (odds ratio 1.58, 95% CI=1.21–2.07, P=0.0008), longer TTF (hazard ratio 0.80, 95% CI=0.68–0.92, P=0.003) and better OS (hazard ratio 0.81, 95% CI=0.67–0.99, P=0.04). However, even in patients with ⩽5% mutation fraction, response rate was 34%. Females had longer TTF (P=0.02).Conclusions:EGFR mutation fraction in tumour samples was significantly associated with response, TTF and OS. Despite this, no lower level of mutation fraction was detected for which EGFR TKI should be withheld in those with activating EGFR mutations.

Adjuvant radiotherapy cannot remediate a positive resection margin. Given these results, consideration for revision surgery should be considered for a positive deep margin. Frozen section analysis may help to define the margins in this invasive and aggressive disease.

No abstract