Differential diagnostic significance of epithelial and stromal CD10 expression in tumors of trichogenic origin.

BACKGROUND AND OBJECTIVES: The histological differential diagnosis between benign trichogenic skin tumors and basal cell carcinoma may be challenging. We therefore set out to investigate whether expression of CD10, a cell surface protein with neutral endopeptidase activity, might be a suitable marker for the histological differential diagnosis of trichogenic skin tumors. PATIENTS AND METHODS: We immunohistochemically analyzed 119 cases of benign trichogenic skin tumors and basal cell carcinoma. These included 28 nodular and 15 sclerosing basal cell carcinomas, 21 Pinkus tumors, 20 trichoblastomas, nine trichofolliculomas, eleven trichoepitheliomas, five desmoplastic trichoepitheliomas, and ten seborrheic keratoses. RESULTS: The majority of nodular basal cell carcinomas expressed CD10 in tumor cells at the peripheral (22/28 [75 %]). On the other hand, trichoblastomas revealed peripheral CD10 expression in only 10 % (2/20) of cases, whereas 50 % showed central expression (10/20). Peripheral epithelial expression of CD10 was also found in Pinkus tumors (9/21 [42.9 %]) and trichoepithelioma (4/11 [36.4 %]). Desmoplastic trichoepithelioma showed no tumoral CD10 expression at all (0/5 [0 %]), while the majority of sclerosing basal cell carcinomas was positive for CD10 (13/15 [86.7 %]). CONCLUSIONS: Our findings suggest that epithelial expression of CD10 - and not peritumoral stromal CD10 expression, as has been postulated - may well be of differential diagnostic significance. The pattern of distribution of CD10-positive neoplastic cells in particular can be useful in the diagnosis of trichogenic tumors.

p53 immunoexpression in stepwise progression of cutaneous squamous cell carcinoma and correlation with angiogenesis and cellular proliferation.

Multistep carcinogenesis involves loss of function of tumor suppressor proteins such as p53 and induction of angiogenesis. Such mechanisms contribute to cutaneous squamous cell carcinoma progression and may be interconnected. We aimed to explore p53 immunoexpression in spectral stages of cutaneous squamous cell carcinoma and correlate expression to both neovascularization and cellular proliferation. We estimated the percentages of immunostained cells for p53 and Ki67 (proliferation marker) in three groups: 23 solar keratoses, 28 superficially invasive squamous cell carcinomas and 28 invasive squamous cell carcinomas. The Chalkley method was used to quantify the microvascular area by neoangiogenesis (CD105) immunomarker in each group. There was no significant difference for rate of p53- and Ki67-positive cells between groups. Significant positive correlation was found between the CD105 microvascular area and the rate of p53 positive cells in superficially invasive squamous cell carcinoma as well as between the rate of p53- and Ki67-positive cells in invasive squamous cell carcinoma. p53 and Ki67 immunoexpression did not increase with cutaneous squamous cell carcinoma progression. Neovascularization in the initial stage of invasion and proliferative activity in the frankly invasive stage were both associated with p53 immunoexpression. Loss of p53 tumor suppressor function through progressive steps may be directly involved in skin carcinogenesis.

Somatostatin receptor expression in Merkel cell carcinoma as target for molecular imaging.

BACKGROUND: Merkel cell carcinoma (MCC) is a rare cutaneous neoplasm with increasing incidence, aggressive behavior and poor prognosis. Somatostatin receptors (SSTR) are expressed in MCC and represent a potential target for both imaging and treatment. METHODS: To non-invasively assess SSTR expression in MCC using PET and the radiotracers [68Ga]DOTA-D-Phe1-Tyr3-octreotide (DOTATOC) or -octreotate (DOTATATE) as surrogate for tumor burden. In 24 patients with histologically proven MCC SSTR-PET was performed and compared to results of computed tomography (CT). RESULTS: SSTR-PET detected primary and metastatic MCC lesions. On a patient-based analysis, sensitivity of SSTR-PET was 73% for nodal metastases, 100% for bone, and 67% for soft-tissue metastases, respectively. Notably, brain metastases were initially detected by SSTR-PET in 2 patients, whereas liver and lung metastases were diagnosed exclusively by CT. SSTR-PET showed concordance to CT results in 20 out of 24 patients. Four patients (17%) were up-staged due to SSTR-PET and patient management was changed in 3 patients (13%). CONCLUSION: SSTR-PET showed high sensitivity for imaging bone, soft tissue and brain metastases, and particularly in combination with CT had a significant impact on clinical stage and patient management.

Angiolymphoid hyperplasia with eosinophilia and Kimura's disease - a clinical and histopathological comparison.

Angiolymphoid hyperplasia with eosinophilia (ALHE) is a benign vascular neoplasm mainly affecting middle-aged women. Lesions typically affect the head and neck region. ALHE is considered a distinct disease entity different from Kimura's disease, a benign reactive lymphoid proliferation that is predominantly seen in young Asian men although it can affect all ethnic groups. In contrast to ALHE, Kimura's disease is typically associated with peripheral blood eosinophilia, increased serum IgE and lymphadenopathy. Several case reports suggest an overlap between ALHE and Kimura's disease. We review the current literature and discuss whether AHLE and Kimura's disease might represent two extreme variants of the same disease entity.

Microvessel density and expression of vascular endothelial growth factor and its receptors in different subtypes of primary cutaneous B-cell lymphoma.

A proangiogenic micromilieu is associated with a worse prognosis in systemic lymphoma. Hence, targeting the tumour microenvironment and its vasculature has evolved as a promising novel treatment strategy. The role of tumour neoangiogenesis in cutaneous B-cell lymphoma, however, has not yet been elucidated. Therefore, we examined the expression of vascular endothelial growth factor (VEGF) and its receptors VEGFR-1 and VEGFR-2, as well as microvessel density by immunohistochemistry in paraffin-embedded specimens of different subtypes of primary cutaneous B-cell lymphomas, systemic diffuse large B-cell lymphoma, and cutaneous B-cell pseudolymphoma. Primary cutaneous large B-cell lymphoma (PCLBCL) were characterized by significantly higher intratumoral expression levels of VEGF and its receptors in comparison with the indolent lymphoma subtypes. Moreover, PCLBCL exhibited significantly higher intratumoral microvessel counts. Our study provides evidence that the most aggressive subtype of cutaneous B-cell lymphoma, PCLBCL, is characterized by a proangiogenic micromilieu.

Flagellate dermatitis caused by shiitake mushrooms.

Shiitake (Lentinus edodes) is the second most consumed mushroom in the world. It has long been known in Asian medicine for its anticarcinogenic, antihypertensive and serum cholesterol level reduction properties. Nevertheless, the consumption of raw or not well-cooked mushrooms may cause skin eruptions which usually occur 24 to 48 hours after ingestion and are characterized by linearly arranged pruritic erythematous papules and plaques. We present a 36-year-old patient that developed typical symptoms 24 hours after consumption of shiitake mushrooms and summarize therapeutic options and particularities of this disease.

Flagellate dermatitis caused by shiitake mushrooms / Dermatite flagelada após a ingestão de fungos shiitake

Shiitake (Lentinus edodes) is the second most consumed mushroom in the world. It has long been known in Asian medicine for its anticarcinogenic, antihypertensive and serum cholesterol level reduction properties. Nevertheless, the consumption of raw or not well-cooked mushrooms may cause skin eruptions which usually occur 24 to 48 hours after ingestion and are characterized by linearly arranged pruritic erythematous papules and plaques. We present a 36-year-old patient that developed typical symptoms 24 hours after consumption of shiitake mushrooms and summarize therapeutic options and particularities of this disease.

Shiitake (Lentinus edodes) é o segundo tipo de cogumelo mais consumido no mundo. Suas propriedades terapêuticas antitumorais, anti-hipertensivas e redutoras dos níveis elevados de colesterol são há muito conhecidas pela população asiática. Após ingestão desse cogumelo, cru ou malcozido, podem desenvolver-se lesões eritematosas lineares, pruriginosas, que surgem após 24 ou 48 horas em todo o corpo. Apresentamos um paciente de 36 anos com anamnese e clínica típicos, e comentamos as alternativas terapêuticas e nuances dessa dermatose.

Typically atypical: histiocytoid Sweet syndrome, associated with malignancy.

Sweet syndrome (acute febrile neutrophilic dermatosis) is characterized by a dramatic onset of high fever, neutrophilia and typical skin lesions. About 20 % of patients have an associated malignancy, most commonly hematologic diseases. Chronic and paucisymptomatic manifestations of Sweet syndrome may be misdiagnosed or misinterpreted as harmless, resulting in delayed diagnosis. "Atypical" manifestations are especially suspicious for associated malignancies. This is demonstrated by a 39-year old patient with chronic and afebrile disease who was referred to our clinic only after symptoms had persisted for several months. By that point, an underlying nodular lymphocyte predominant Hodgkin's lymphoma had already reached an advanced stage. Skin biopsies revealed dermal infiltrates of histiocytoid cells of myelogenous origin, supporting a diagnosis of histiocytoid Sweet syndrome. Specific cutaneous infiltrates associated with myelogenous leukemia were ruled out.

Angiogenesis in the progression of cutaneous squamous cell carcinoma: an immunohistochemical study of endothelial markers.

OBJECTIVE: To demonstrate the role of angiogenesis in the progression of cutaneous squamous cell carcinoma. INTRODUCTION: Angiogenesis is a pivotal phenomenon in carcinogenesis. Its time course in cutaneous squamous cell carcinoma has not yet been fully established. METHODS: We studied the vascular bed in 29 solar keratoses, 30 superficially invasive squamous cell carcinomas and 30 invasive squamous cell carcinomas. The Chalkley method was used to quantify the microvascular area by comparing panendothelial (CD34) with neoangiogenesis (CD105) immunohistochemical markers. The vascular bed from non-neoplastic adjacent skin was evaluated in 8 solar keratoses, 10 superficially invasive squamous cell carcinomas and 10 invasive squamous cell carcinomas. RESULTS: The microvascular area in CD105-stained specimens significantly increased in parallel with cutaneous squamous cell carcinoma progression. However, no differences between groups were found in CD34 sections. Solar keratosis, superficially invasive squamous cell carcinoma and invasive squamous cell carcinoma samples showed significant increases in microvascular area for both CD34- and CD105-stained specimens compared with the respective adjacent skin. DISCUSSION: The angiogenic switch occurs early in the development of cutaneous squamous cell carcinoma, and the rate of neovascularization is parallel to tumor progression. In contrast to panendothelial markers, CD105 use allows a dynamic evaluation of tumor angiogenesis. CONCLUSION: This study demonstrated the dependence of skin carcinogenesis on angiogenesis.

ERCC5 p.Asp1104His and ERCC2 p.Lys751Gln polymorphisms are independent prognostic factors for the clinical course of melanoma.

Genetic variants in DNA repair enzymes contribute to the susceptibility to cutaneous melanoma; consequently, we analyzed whether common nonsynonymous single-nucleotide polymorphisms in DNA repair enzyme genes might also influence the course of disease. To this end, we determined eight polymorphisms of seven different DNA repair enzymes in 742 patients with cutaneous melanoma, and correlated these with overall survival. Univariate Cox proportional hazards model analyses revealed that ERCC5 (XPG) 1104 His/His was significantly associated with impaired survival. Indeed, the univariate hazard ratio (HR) was 2.8 times higher for patients with ERCC5 1104 His/His (P<0.001) compared with ERCC5 1104 Asp/Asp. Accordingly, the 5-year survival rate was 55% (95% confidence interval 43-71) for patients with ERCC5 1104 His/His, whereas 82% (95% confidence interval 78-86) of patients with ERCC5 1104 Asp/Asp were still alive at this time. Importantly, adjusted Cox regression analysis not only confirmed ERCC5 1104 His/His as an independent prognostic factor (multivariate HR=4.5; P<0.001), but also revealed the significant impact of ERCC2 (XPD) 751 Gln/Gln on prognosis, with a 2.2-fold increased HR compared with ERCC2 751 Lys/Lys (P=0.009). Thus, ERCC5 codon 1104 and ERCC2 codon 751 polymorphisms are independent prognostic factors in patients with cutaneous melanoma.

A red cheek as first clinical sign of a sebaceous lymphadenocarcinoma of the parotid gland with lymphangiosis carcinomatosa and lymph node metastases.

Sebaceous lymphadenoma is a rare benign neoplasm presenting predominantly in the parotid gland or in periparotid lymph nodes. It rarely transforms into a malignant tumor. We present a sebaceous lymphadenoma with an unusual clinical presentation with a malignant component, infiltration of lymph nodes, and lymphangiosis carcinomatosa. Sebaceous lymphadenoma usually presents as a well-circumscribed, painless, infraauricular mass. In our 87-years-old male patient, the clinical presentation was confluent reddish livid plaques at the left cheek and the left neck. In addition, cervical lymph node metastases were suspected. After skin biopsy, the tumor was excised by parotidectomy, skin excision, and neck dissection followed by a postoperative radiotherapy. To our knowledge, this is the sixth reported case of sebaceous lymphadenocarcinoma and the first case presenting with cervical lymph node metastases and dermatological symptoms revealing lymphangiosis carcinomatosa.

Primary cutaneous diffuse large B-cell lymphoma, leg-type, treated with a modified R-CHOP immunochemotherapy - diagnostic and therapeutic challenges.

BACKGROUND: Primary cutaneous diffuse large B-cell lymphoma (PCLBCL) represents a rare subtype among primary cutaneous B-cell lymphoma exhibiting a characteristic genetic background, an aggressive clinical course and a high relapse rate under different therapeutic regimen. Therefore, PCLBCL has a rather restricted prognosis. PATIENTS AND METHODS: Four patients with PCLBCL were treated at our institution with age- and toxicity-adapted first-line immunochemotherapy with rituximab and modified CHOP (cyclophosphamid, vincristin, liposomal doxorubicin, prednisolon). On relapse, the same regimen with R-CHOP or different antineoplastic strategies (radiation, polychemotherapy, immunotherapy, stem cell transplantation) were applied. Toxicity, clinical response and overall survival was documented. RESULTS: Under this regimen, clinical response to modified R-CHOP was achieved in all patients with tolerable toxicity - however, being characterized by a rapid disease progression with inconsistent response towards the subsequent therapeutic armentarium and unsecure impact on overall survival. CONCLUSIONS: So far, it is still unknown, if an extensive multimodal therapy for PBLBCL improves overall survival. Immunochemotherapy with R-CHOP currently represents the most effective treatment.