Paraneoplastic hyperleucocytosis in a melanoma patient after initiation of ipilimumab and nivolumab combination therapy

Abstract Background Paraneoplastic hyperleucocytosis (PH) is sporadically seen in patients with advanced solid tumors. Case presentation We report a female patient with disseminated melanoma metastases. Two days after the first dosage of combined immunotherapy using the cytotoxic T lymphocyte antigen-4 (CTLA-4) blocker ipilimumab and the programmed death receptor-1 (PD-1) blocker nivolumab the patient developed asymptomatic hyperleucocytosis (over 120.000 leucocytes per μl) associated with elevated granulocyte colony-stimulating factor blood levels. Hematological and infectious disorders could be ruled out. Although paraneoplastic hyperleucocytosis spontaneously resolved she died from progressive disease about 60 days after start of treatment. Conclusions PH is extremely rare in malignant melanoma, however, most patients who developed this complication had preceding immunotherapies such as interleukin-2. The latter observation and the fact that our patient developed PH rapidly after initiation of ipilimumab and nivolumab immunotherapy indicate an immune-mediated mechanism which may trigger PH under unknown circumstances. The development of paraneoplastic hyperleucocytosis indicates a very poor prognosis

Primary Cutaneous CD30+ Anaplastic Large T Cell Lymphoma in a Patient Treated with Cyclosporine for Actinic Reticuloid

Actinic reticuloid (AR)—a subtype of chronic actinic dermatitis—clinically and histopathologically shows lymphoma-like features. We report a male patient initially diagnosed with erythrodermic cutaneous T cell lymphoma (CTCL) who developed severe broadband photosensitivity. Clinical evaluation, histopathology, and phototesting were consistent with AR. The patient was treated with cyclosporine 150–300 mg/d. Under this therapy, he developed several times primary cutaneous anaplastic large cell lymphomas (C-ALCL) which in part tended to regress spontaneously under cyclosporine reduction. The association between cyclosporine treatment and development of C-ALCL and other CD30+ lymphoproliferative disorders has previously been reported in patients with atopic dermatitis, psoriasis, and transplant patients. In conclusion, the present case highlights the difficulties arising in the distinction between AR and CTCL and shows that long-term cyclosporine treatment may cause C-ALCL development in AR as well

Multivariate analysis of prognostic factors in patients with nodular melanoma

Purpose!#!Nodular melanoma (NM) is associated with worse disease outcome when compared to superficial spreading melanoma (SSM). We aimed to perform a single-center analysis of prognostic factors in patients with NM and compare the data with SSM patients.!##!Methods!#!We studied 228 patients with NN and 396 patients with SSM. Patients with in situ melanomas or stage IV at diagnosis were not included in the study. Data were analyzed using the Mann-Whitney test, Chi-square test, Kaplan-Meier curves including the log-rank test, and logistic regression model.!##!Results!#!When compared to patients with SSM, patients with NM had less likely lower Clark level, higher tumor thickness, less likely tumor regression, more often ulcerated tumors, and less likely a history of precursor lesions such as a nevus. Within a 5-year follow-up we observed significantly more disease relapses and deaths in NM patients than in SSM patients. On multivariate analysis, disease relapse in NM patients was independently predicted by tumor thickness and positive SLNB, whereas melanoma-specific death of NM patients was independently predicted by male sex and tumor thickness. Histologic regression also remained in the logistic regression model as a significant independent negative predictor of NM death.!##!Conclusions!#!We did not observe that NM subtype was per se a significant independent predictor for disease relapse or melanoma-specific death. Among the well-known prognostic factors such as tumor thickness and male sex, NM is also associated with other unfavorable factors such as absence of regression

Cancer and immune checkpoint inhibitor treatment in the era of SARS-CoV-2 infection.

Whether cancer patients receiving immune checkpoint inhibitors (ICI) are at an increased risk of severe infection and mortality during the corona pandemic is a hotly debated topic that will continue to evolve. Here, we summarize and discuss current studies regarding COVID-19 and anti-cancer treatment with an emphasis on ICI. Importantly, several lines of evidence suggest that patients currently treated with ICI do not display an increased vulnerability to infection with SARS-CoV-2. Data regarding morbidity and mortality associated with COVID-19 in cancer patients receiving ICI are less clear and often conflicting. Although mostly based on experimental data, it is possible that ICI can promote the exacerbated immune response associated with adverse outcome in COVID-19 patients. On the other hand, mounting evidence suggests that ICI might even be useful in the treatment of viral infections by preventing or ameliorating T cell exhaustion. In this context, the right timing of treatment might be essential. Nevertheless, some cancer patients treated with ICI experience autoimmune-related side effects that require the use of immunosuppressive therapies, which in turn may promote a severe course of infection with SARS-CoV-2. Although there is clear evidence that withholding ICI will have more serious consequences, further studies are urgently needed in to better evaluate the effects of ICI in patients with COVID-19 and the use of ICI during the corona pandemic in general

Protein expression of prognostic genes in primary melanoma and benign nevi

Purpose!#!To evaluate the protein expression characteristics of genes employed in a recently introduced prognostic gene expression assay for patients with cutaneous melanoma (CM).!##!Methods!#!We studied 37 patients with CM and 10 with benign (melanocytic) nevi (BN). Immunohistochemistry of primary tumor tissue was performed for eight proteins: COL6A6, DCD, GBP4, KLHL41, KRT9, PIP, SCGB1D2, SCGB2A2.!##!Results!#!The protein expression of most markers investigated was relatively low (e.g., DCD, KRT9, SCGB1D2) and predominantly cytoplasmatic in melanocytes and keratinocytes. COL6A6, GBP4, and KLHL41 expression was significantly enhanced in CM when compared to BN. DCD protein expression was significantly correlated with COL6A6, GBP4, and KLHL41. GBP4 was positively correlated with KLHL41 and inversely correlated with SCGB2B2. The latter was also inversely correlated with serum S100B levels at time of initial diagnosis. The presence of SCGB1D2 expression was significantly associated with ulceration of the primary tumor. KRT9 protein expression was significantly more likely found in acral lentiginous melanoma. The presence of DCD expression was less likely associated with superficial spreading melanoma subtype but significantly associated with non-progressive disease. The absence of SCGB2A2 expression was significantly more often observed in patients who did not progress to stage III or IV.!##!Conclusions!#!The expression levels observed were relatively low but differed in part with those found in BN. Even though we detected some significant correlations between the protein expression levels and clinical parameters (e.g., CM subtype, course of disease), there was no major concordance with the protective or risk-associated functions of the corresponding genes included in a recently introduced prognostic gene expression assay