Malignant neuroectodermal tumor with melanocytic and rhabdomyoblastic differentiation

Malignant melanoma can metastasize widely and vary significantly in its histological appearance; it rarely presents as a deep-seated mass without an obvious primary site elsewhere. Malignant peripheral nerve sheath tumor (MPNST) is a high-grade sarcoma characterized by conventional and epithelioid subtypes. MPNST can demonstrate heterologous differentiation, usually in the form of osteosarcomatous, chondrosarcomatous, or rhabdomyosarcomatous differentiation. MPNST does not harbor true melanocytic differentiation, although epithelioid MPNST typically is diffusely S-100 protein positive and superficially can resemble malignant melanoma. An unusual intra-abdominal mass was recently encountered with features of both melanoma and conventional or epithelioid MPNST containing a fascicular spindle cell component, an epithelioid component with melanocytic differentiation, as well as a rhabdomyosarcomatous component. The terminology “malignant neuroectodermal tumor with melanocytic and rhabdomyoblastic differentiation” is proposed to describe this neoplasm, reflecting the unusual concomittant lines of differentiation as well as offering a possible rationale for nosologically challenging aspects of this neoplasm

Expression of MAGE-C1/CT7 and MAGE-C2/CT10 Predicts Lymph Node Metastasis in Melanoma Patients

MAGE-C1/CT7 and MAGE-C2/CT10 are members of the large MAGE family of cancer-testis (CT) antigens. CT antigens are promising targets for immunotherapy in cancer because their expression is restricted to cancer and germ line cells and a proportion of cancer patients presents with immune responses against CT antigens, which clearly demonstrates their immunogenicity. This study investigates the expression of MAGE-C1/CT7 and MAGE-C2/CT10 in primary and metastatic melanoma. Immunohistochemical staining of tissue microarrays that consisted of 59 primary malignant melanomas of the skin, 163 lymph node and distant melanoma metastases and 68 melanoma cell lines was performed. We found MAGE-C1/CT7 expression in 15 out of 50 (24%) primary melanomas and 15 out of 50 (24%) cell lines, whereas MAGE-C2/CT10 was detected in 17 out of 51 (33%) primary melanomas and 14 out of 68 (17%) cell lines. MAGE-C1/CT7 and MAGE-C2/CT10 were both detected in 40% of melanoma metastases. Patients with MAGE-C1/CT7 or MAGE-C2/CT10 positive primary melanoma had significantly more lymph node metastases (p = 0.005 and p<0.001, resp.). Prediction of lymph node metastasis by MAGE-C1/CT7 and MAGE-C2/CT10 was independent of tumor cell proliferation rate (Ki67 labeling index) in a multivariate analysis (p = 0.01). Our results suggest that the expression of MAGE-C1/CT7 and MAGE-C2/CT10 in primary melanoma is a potent predictor of sentinel lymph node metastasis

Ki-67 expression is superior to mitotic count and novel proliferation markers PHH3, MCM4 and mitosin as a prognostic factor in thick cutaneous melanoma

<p>Abstract</p> <p>Background</p> <p>Tumor cell proliferation is a predictor of survival in cutaneous melanoma. The aim of the present study was to evaluate the prognostic impact of mitotic count, Ki-67 expression and novel proliferation markers phosphohistone H3 (PHH3), minichromosome maintenance protein 4 (MCM4) and mitosin, and to compare the results with histopathological variables.</p> <p>Methods</p> <p>202 consecutive cases of nodular cutaneous melanoma were initially included. Mitotic count (mitosis per mm²) was assessed on H&E sections, and Ki-67 expression was estimated by immunohistochemistry on standard sections. PHH3, MCM4 and mitosin were examined by staining of tissue microarrays (TMA) sections.</p> <p>Results</p> <p>Increased mitotic count and elevated Ki-67 expression were strongly associated with increased tumor thickness, presence of ulceration and tumor necrosis. Furthermore, high mitotic count and elevated Ki-67 expression were also associated with Clark's level of invasion and presence of vascular invasion. High expression of PHH3 and MCM4 was correlated with high mitotic count, elevated Ki-67 expression and tumor ulceration, and increased PHH3 frequencies were associated with tumor thickness and presence of tumor necrosis. Univariate analyses showed a worse outcome in cases with elevated Ki-67 expression and high mitotic count, whereas PHH3, MCM4 and mitosin were not significant. Tumor cell proliferation by Ki-67 had significant prognostic impact by multivariate analysis.</p> <p>Conclusions</p> <p>Ki-67 was a stronger and more robust prognostic indicator than mitotic count in this series of nodular melanoma. PHH3, MCM4 and mitosin did not predict patient survival.</p

Immunhistochemische Analyse von Bcl-2, nukleärem S100A4, MITF und Ki67 zur Risikostratifizierung von Melanomen im Frühstadium - ein kombinierter immunhistochemischer Score

HINTERGRUND UND ZIELSETZUNG: Patienten mit malignen Melanomen im Frühstadium haben ein unterschiedliches Gesamtüberleben. Derzeit existieren keine etablierten prognostischen Marker. Unser Ziel war es, zu einem besseren Verständnis der potenziell prognostischen immunhistochemischen Marker für die Risikostratifizierung beizutragen. PATIENTEN UND METHODEN: 161 operativ entfernte maligne Melanome (Stadien pT1 und pT2) wurden immunhistochemisch auf die Expression von 20 verschiedenen Proteinen untersucht. Die Ergebnisse wurden mit dem Gesamtüberleben korreliert. Die Kohorte wurde randomisiert in eine Entdeckungs- und eine Validierungskohorte aufgeteilt. ERGEBNISSE: Eine hohe Bcl-2-Expression, eine hohe nukleäre S100A4-Expression und ein Ki67-Proliferationsindex von ≥ 20 % waren mit einem kürzeren Gesamtüberleben assoziiert. Eine starke MITF-Immunreaktivität erwies sich als prädiktiv für eine gute Prognose. Die Kombination dieser vier Marker ergab einen Multimarker-Score mit signifikantem prognostischem Wert in der multivariaten Überlebensanalyse (HR: 3,704; 95 %-KI 1,484-9,246; p = 0,005). Zusätzlich gelang es mit dem Score, drei prognostische Gruppen zu identifizieren: eine Niedrigrisikogruppe mit sehr guten Gesamtüberlebensraten (Fünf-Jahres-Überlebensrate 100 %), eine Gruppe mit mittlerem Risiko (Fünf-Jahres-Überlebensrate 81,8 %) und eine Hochrisikogruppe (Fünf-Jahres-Überlebensrate 52,6 %). Der prognostische Aussagewert bestätigte sich in der Validierungskohorte. SCHLUSSFOLGERUNGEN: Die kombinierte immunhistochemische Analyse von Bcl-2, nukleärem S100A4, Ki67 und MITF könnte zu einer besseren Risikostratifizierung bei Patienten mit malignen Melanomen im Frühstadium beitragen