Epithelial damage and tissue γδ T cells promote a unique tumor-protective IgE response.

IgE is an ancient and conserved immunoglobulin isotype with potent immunological function. Nevertheless, the regulation of IgE responses remains an enigma, and evidence of a role for IgE in host defense is limited. Here we report that topical exposure to a common environmental DNA-damaging xenobiotic initiated stress surveillance by γδTCR+ intraepithelial lymphocytes that resulted in class switching to IgE in B cells and the accumulation of autoreactive IgE. High-throughput antibody sequencing revealed that γδ T cells shaped the IgE repertoire by supporting specific variable-diversity-joining (VDJ) rearrangements with unique characteristics of the complementarity-determining region CDRH3. This endogenous IgE response, via the IgE receptor FcεRI, provided protection against epithelial carcinogenesis, and expression of the gene encoding FcεRI in human squamous-cell carcinoma correlated with good disease prognosis. These data indicate a joint role for immunosurveillance by T cells and by B cells in epithelial tissues and suggest that IgE is part of the host defense against epithelial damage and tumor development.

Transcriptomic analysis of cutaneous squamous cell carcinoma reveals a multigene prognostic signature associated with metastasis.

BACKGROUND: Metastasis of cutaneous squamous cell carcinoma (cSCC) is uncommon. Current staging methods are reported to have sub-optimal performances in metastasis prediction. Accurate identification of patients with tumors at high risk of metastasis would have a significant impact on management. OBJECTIVE: To develop a robust and validated gene expression profile signature for predicting primary cSCC metastatic risk using an unbiased whole transcriptome discovery-driven approach. METHODS: Archival formalin-fixed paraffin-embedded primary cSCC with perilesional normal tissue from 237 immunocompetent patients (151 nonmetastasizing and 86 metastasizing) were collected retrospectively from four centers. TempO-seq was used to probe the whole transcriptome and machine learning algorithms were applied to derive predictive signatures, with a 3:1 split for training and testing datasets. RESULTS: A 20-gene prognostic model was developed and validated, with an accuracy of 86.0%, sensitivity of 85.7%, specificity of 86.1%, and positive predictive value of 78.3% in the testing set, providing more stable, accurate prediction than pathological staging systems. A linear predictor was also developed, significantly correlating with metastatic risk. LIMITATIONS: This was a retrospective 4-center study and larger prospective multicenter studies are now required. CONCLUSION: The 20-gene signature prediction is accurate, with the potential to be incorporated into clinical workflows for cSCC.

Rare cutaneous metastasis from sarcomatoid carcinoma of lung.

We present the case of a 57-year-old woman diagnosed with stage 4 sarcomatoid carcinoma of the lung who concurrently developed a scalp lesion, thought to be a cyst, which continued to grow and ulcerate. Excision revealed a rare case, only four previously reported in the literature, of metastatic sarcomatoid carcinoma of the lung. While a very unusual case, we would like to emphasise the importance of considering skin metastases when presented with unusual skin lesions, and importantly listening to the patient's concerns, showing empathy and respecting their autonomy and referring to an appropriate specialist when considering the management of what may seem to be a minor skin report.

Cutaneous malakoplakia presenting as a groin swelling and graft failure.

Malakoplakia (from the Greek malakos, 'soft' and plakos 'plaque') is a granulomatous inflammatory condition, commonly presenting as a plaque in the genitourinary system, but has been shown to affect a wide variety of structures including the skin. Presentation is varied and a high degree of clinical suspicion is needed to make a diagnosis. We report a case of cutaneous malakoplakia presenting as an inguinal swelling in a 48-year-old kidney transplant patient with temporally associated graft dysfunction. New groin swelling in an immunosuppressed patient often prompts investigation centred on a malignant cause. While this is often appropriate, less common infectious and inflammatory causes should be considered. This case highlights the importance of thorough workup and investigation, including histopathology, in immunosuppressed cohorts and acts as a reminder that less common and more complex diagnoses warrant consideration in this group.

Value of sentinel node status as a prognostic factor in melanoma: prospective observational study.

OBJECTIVE: To establish the prognostic value of knowledge of sentinel node status in melanoma. DESIGN: Single centre prospective observational study, with sentinel nodes identified by lymphoscintigraphy, gamma probe, and intraoperative blue dye and examined by both conventional histopathology and immunopathology. SETTING: Specialist surgical service in west of Scotland. PARTICIPANTS: 482 patients with melanoma who consented to sentinel node biopsy in 1996-2003. MAIN OUTCOME MEASURE: Time to recurrence of or death from melanoma. RESULTS: Of 472 patients who consented to sentinel node biopsy and in whom at least one sentinel node was identified, 367 (78%) had no tumour in the sentinel node. At mean follow-up of 42 months, 299 (82%) of this group were alive and free from disease, 24 were alive with melanoma recurrence, and 31 had died of melanoma. Of 105 patients with a positive sentinel node biopsy, 44 (42%) were alive and disease free, 12 were alive with recurrence, and 46 had died of melanoma. The survival difference between patients who were negative and those who were positive for tumour in the sentinel node was highly significant at all thickness levels over 1.0 mm (P < 0.001). Multivariate analysis showed that sentinel node status was independent of tumour thickness and ulceration. 71/105 (68%) patients with a positive sentinel node had a negative completion lymphadenectomy, and 44/71 (62%) were alive and disease free at follow-up; 34 patients with a positive sentinel node had further nodes involved, and only 4 (12%) were disease free (P < 0.001). 16 patients (13 sentinel node biopsy positive; 3 negative) died of other causes. CONCLUSION: Sentinel node status is a highly significant predictor of prognosis in melanoma and should be considered in adjuvant studies. However, it should not be regarded as a standard of care until mature data from ongoing randomised trials are available.