Tumours and tumour-like lesions of myofibroblasts may present diagnostic difficulty because of their rarity and because of uncertainties in identifying the myofibroblast. The objectives of this review are to provide a definition of the myofibroblast and an account of its biology for facilitating an understanding of the cell and of myofibroblastic lesions; and to describe, in the context of common diagnostic problems, the features of benign and malignant myofibroblastic lesions. The main characteristics of the myofibroblast include a spindled or stellate morphology; immunostaining for alpha-smooth muscle actin and the extra domain A variant of cellular fibronectin; and an ultrastructure of rough endoplasmic reticulum, peripheral contractile filaments and the cell-to-matrix junction known as the fibronexus. On this basis, lesions traditionally regarded as myofibroblastic are shown to vary in their level of differentiation, and some appear to be smooth muscle rather than myofibroblastic. Immunohistochemistry and electron microscopy, used together, are emphasised as being important for maximum diagnostic confidence in some myofibroblastic lesions.

We previously demonstrated that circulating tumour cells (CTCs) are detectable by the MelCAM and high molecular weight melanoma-associated antigen (HMW-MAA)-dependent CellSearch platform. However, CTCs which do not express these capture and detection markers are not detectable by CellSearch. Consequently, we explored the use of isolation by size of epithelial tumour cells (ISET), a marker independent, filtration-based device to determine the prevalence and heterogeneity of CTCs in metastatic cutaneous melanoma patients. Ninety patients were prospectively recruited and blood samples taken before treatment. Patients' blood was filtered using the ISET platform. CTCs were enumerated using dual immunohistochemistry with positive selection by S100 expression and exclusion of leucocytes and endothelial cells expressing CD45 or CD144, respectively. A panel of markers (Melan-A, MITF, MelCAM, high molecular melanoma-associated antigen, CD271 and MAGEC) was also examined. Fifty-one patients (57%) had CTCs (range 1-44 CTCs/4 ml blood) and 12 patients also had circulating tumour microemboli. Seven patients had S100- CTCs, 11 patients' CTCs were S100+ and 33 patients had S100+ and S100- CTCs. Substantial intrapatient and interpatient heterogeneity was observed for all other melanoma-associated markers. CTCs in metastatic cutaneous melanoma are detectable using the flexible marker-independent ISET platform. CTCs display significant marker expression heterogeneity implying that marker-dependent platforms would not detect all CTCs and multimarker assays are now required to reveal the biological significance of this CTC heterogeneity.

This is the first study to detect GPC3-positive CTCs in HCC, important for drug development with this target. The significant association of circulating CK18 with OS in HCC further exemplifies the utility of circulating biomarkers in cancer.

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Four cases of CD30-positive T-cell lymphoproliferative disorder (CD30+ LPD) of the oral mucosa are described. This article aims to draw attention to this entity and to emphasize its usual benign clinical behavior despite its resemblance to T-cell lymphoma. All the patients were adults. Three of the lesions were on the dorsal surface of the tongue and 1 affected the buccal mucosa. All biopsies showed a dense lymphoid infiltrate composed of CD30+ atypical T cells with a polymorphous infiltrate in the background, which included eosinophils. In 1 case, monoclonal T-cell expansion was detected by molecular techniques. Three cases tested for Epstein-Barr virus were all negative. It is concluded that primary CD30+ T-cell LPD of the oral mucosa can be regarded as the oral counterpart of cutaneous CD30+ LPD such as lymphomatoid papulosis or anaplastic large cell lymphoma. Recognition of the condition is important to avoid overtreatment.

Background:Despite high metastasis rates, adjuvant/neoadjuvant systemic therapy for localised soft tissue sarcoma (STS) is not used routinely. Progress requires tailoring therapy to features of tumour biology, which need exploration in well-documented cohorts. Hypoxia has been linked to metastasis in STS and is targetable. This study evaluated hypoxia prognostic markers in the phase III adjuvant radiotherapy VorteX trial.Methods:Formalin-fixed paraffin-embedded tumour biopsies, fresh tumour/normal tissue and blood were collected before radiotherapy. Immunohistochemistry for HIF-1α, CAIX and GLUT1 was performed on tissue microarrays and assessed by two scorers (one pathologist). Prognostic analysis of disease-free survival (DFS) used Kaplan–Meier and Cox regression.Results:Biobank and outcome data were available for 203 out of 216 randomised patients. High CAIX expression was associated with worse DFS (hazard ratio 2.28, 95% confidence interval: 1.44–3.59, P<0.001). Hypoxia-inducible factor-1α and GLUT1 were not prognostic. Carbonic anhydrase IX remained prognostic in multivariable analysis.Conclusions:The VorteX-Biobank contains tissue with linked outcome data and is an important resource for research. This study confirms hypoxia is linked to poor prognosis in STS and suggests that CAIX may be the best known marker. However, overlap between single marker positivity was poor and future work will develop an STS hypoxia gene signature to account for tumour heterogeneity.

Purpose: Cancer susceptibility and mortality are higher in males, and the mutational and transcriptomic landscape of cancer differs by sex. The current assumption is that men are at higher risk of epithelial cancers as they expose more to carcinogens and accumulate more damage than women. We present data showing women present with less aggressive primary cutaneous squamous cell carcinoma (cSCC) and early strong immune activation. Experimental Design: We explored clinical and molecular sexual disparity in immunocompetent and immunosuppressed patients with primary cSCC (N = 738, N = 160), advanced-stage cSCC (N = 63, N = 20) and FVB/N mice exposed to equal doses of DMBA, as well as in human keratinocytes by whole-exome, bulk, and single-cell RNA sequencing. Results: We show cSCC is more aggressive in men, and immunocompetent women develop mild cSCC, later in life. To test whether sex drives disparity, we exposed male and female mice to equal doses of carcinogen, and found males present with more aggressive, metastatic cSCC than females. Critically, females activate cancer immune-related expression pathways and CD4 and CD8 T-cell infiltration independently of mutations, a response that is absent in prednisolone-treated animals. In contrast, males increase the rate of mitosis and proliferation in response to carcinogen. Women's skin and keratinocytes also activate immune-cancer fighting pathways and immune cells at UV radiation–damaged sites. Critically, a compromised immune system leads to high-risk, aggressive cSCC specifically in women. Conclusions: This work shows the immune response is sex biased in cSCC and highlights female immunity offers greater protection than male immunity.

We describe 2 new cases of malignant melanoma with divergent rhabdomyoblastic differentiation occurring in adult patients. The patients were women aged 67 and 51 years with primary cutaneous and uterine cervical melanoma, respectively. Rhabdomyoblastic differentiation in melanoma is very rare in adult patients, and to our knowledge, only 7 such cases have been described in the world literature, of which only 4 have conclusive documentation of the presence of rhabdomyoblastic differentiation. We present the fifth and sixth cases of adult melanomas with conclusive divergent rhabdomyoblastic differentiation, including the first noncutaneous (cervical) case; we also review the literature and highlight the potential for underrecognition of this phenomenon.