[Bronchial asthma and allergic rhinitis-The skin sample reveals a severe systemic disease]. / Asthma bronchiale und allergische Rhinitis ­ die Hautprobe offenbart eine schwerwiegende Systemerkrankung.

This article reports the case of a 30-year-old female patient who suffered for many years from initially unspecific symptoms, such as recurrent, nonallergic and noninfectious sinusitis, late-onset bronchial asthma and pronounced lymphadenopathy; however, the correct diagnosis of eosinophilic granulomatosis with polyangiitis (EGPA) could only be made by histological investigations after the appearance of skin symptoms. The EGPA is a severe systemic disease which, if left untreated, can cause multiple organ damage and even be fatal. With adequate treatment the disease is mild in more than 90% of cases and patients can even completely recover. By making the correct diagnosis, the patient could be successfully treated and the risk of late manifestations and subsequent damage with a potentially fatal outcome was reduced.

Lymphatic vessel involvement in primary cutaneous B-cell lymphoma: A common finding?

BACKGROUND: Cutaneous B-cell lymphoma (CBCL) is part of dermatopathological routine diagnostics. However, in contrast to cutaneous T-cell lymphomas, there are only a few studies on the prevalence and possible clinical impact of lymphatic vessel involvement. Therefore, this pilot study aimed to quantify the prevalence of lymphovascular involvement in CBCL and to assess the association between lymphovascular involvement and recurrence. METHODS: Thirty-nine patients from two tertiary care hospitals diagnosed with CBCL were retrospectively identified and their biopsies were histopathologically examined for the presence of lymphatic vessel involvement using H&E stain, and CD20 and D2-40 immunohistochemistry. Clinical data were retrieved from our digital documentation files. RESULTS: Thirty patients were included in the evaluation (nPCFCL = 15, nPCMZL = 10, and nPCLBCL = 5). Lymphovascular involvement occurred in all three types of lymphoma and was present in 14/30 specimens. The presence of lymphatic involvement did not show a significant impact on recurrence rate (p = 0.150). CONCLUSIONS: This immunohistochemical pilot study shows that lymphovascular involvement is a relatively frequent finding in primary CBCL. Although no definitive conclusion can be drawn from our findings because of the small sample size, there were no strong signs of tendencies for recurrence in either group. Future studies with larger sample size are warranted to assess the possible clinical implications.

Metabolic Signature of Atypical Fibroxanthoma and Pleomorphic Dermal Sarcoma: Expression of Hypoxia-inducible Factor-1α and Several of Its Downstream Targets.

Metabolic reprogramming mediated by hypoxia-inducible factors play a crucial role in many human cancers. HIF-1α is activated under hypoxic conditions and is considered a key regulator of oxygen homoeostasis during tumor proliferation under hypoxia. Aim of this research was to analyze the immunohistochemical expression of HIF-1α, VEGF-A, Glut-1, MCT4, and CAIX in atypical fibroxanthoma (AFX) and pleomorphic dermal sarcoma (PDS). 21 paraffin-embedded AFX and 22 PDS were analysed by immunohistochemistry, namely HIF-1α, VEGF-A (referred to as VEGF throughout the manuscript), Glut-1, MCT4, and CAIX. To quantify the protein expression, we considered the percentage of positive tumor cells (0: 0%, 1: up to 1%, 2: 2-10%, 3: 11-50%, 4: >50%) in relation to the staining intensity (0: negative, 1: low, 2: medium, 3: strong). HIF-1α expression (mean ± SD) in AFX (9.33±2.92) was significantly stronger than that in PDS (5.90±4.38; P= 0.007), whereas the expression of VEGF, Glut-1, MCT4, and CAIX did not show differences between AFX and PDS. When comparing all tumors without subgroup stratification, the expression of HIF-1α (P= 0.044) and MCT4 (P= 0.036) was significantly stronger in ulcerated tumors than in tumors without ulceration. Our findings provide the first evidence that HIF-1α-induced metabolic reprogramming may contribute to the pathogenesis of AFX and PDS. HIF-1α expression seems to be higher in AFX than in PDS, and ulcerated tumors show higher expression levels of HIF-1α and MCT4 irrespective of the diagnosis.

[Immunohistochemical analysis of a hypoxia-associated signature in melanomas with positive and negative sentinel lymph nodes : Hypoxia-associated signature of primary cutaneous melanomas]. / Immunhistochemische Analyse einer Hypoxie-assoziierten Signatur in Melanomen mit positivem und negativem Schildwächterlymphknoten : Hypoxie-assoziierte Signatur primär kutaner Melanome.

Metabolic reprogramming mediated by hypoxia-inducible factors and its downstream targets plays a crucial role in many human malignancies. Excessive proliferation of tumor cells under hypoxic conditions leads to metabolic reprogramming and altered gene expression enabling tumors to adapt to their hypoxic environment. Here we analyzed the metabolic signatures of primary cutaneous melanomas with positive and negative sentinel node status in order to evaluate potential differences in their metabolic signature. We found a positive correlation of the expression of glucose transporter 1 (GLUT-1) with tumor thickness and ulceration in all melanomas with subgroup analyses as well as in the subgroup with a negative sentinel node. Furthermore, the expression of vascular endothelial growth factor (VEGF) was positively correlated with the presence of ulceration in melanomas with positive sentinel node.

Improvement in Quality of Life and Pain in Patients With Hidradenitis Suppurativa After Wide Local Excision: A Prospective Study.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease that affects patients' quality of life (QoL). OBJECTIVE: To investigate changes in QoL in patients with HS after wide local excision (WLE) and to examine the level of pain, rate of postoperative complications, recurrences, and the time to complete wound closure. METHODS: Fifty-five patients were enrolled in this prospective study. All patients underwent WLE of HS, followed by secondary wound healing. Dermatologic Life Quality Questionnaire, pain, and wound size were measured 1 day, 3 weeks, 3 months, and 6 months after surgery. RESULTS: Dermatologic Life Quality Questionnaire and pain scores (mean ± SD) improved significantly (both p < .001) from 14.5 ± 7.3 and 3.7 ± 2.8 at baseline to 5.8 ± 6.9 and 0.8 ± 1.7, 6 months postoperatively, respectively. Wounds were closed completely by secondary intention after 4.4 ± 2.8 months. Sixteen patients (29.1%) experienced postoperative complications, local recurrences in the treated sites were observed in 11 patients (20%), and new lesions in untreated sites were observed in 5 cases (9.1%). CONCLUSION: Wide local excision significantly improves patients' QoL and pain, and, given its low rate of recurrence and complications, should be considered as a first-line therapy, especially in patients with higher Hurley stages.

Dysplastic Nevi: Morphology and Molecular and the Controversies In-between.

Dysplastic nevi are distinctive melanocytic lesions in the larger group of atypical nevi. They often are multiple and sporadic with genetic features intermediate between common acquired nevi and melanoma. Dysplastic nevi may be multiple, familial, and seen in patients with familial melanoma syndrome. Although their behavior is benign, they rarely represent a precursor to melanoma. If clinically suspicious, dysplastic nevi should be removed for adequate histopathologic examination and to exclude possibility of melanoma. Partial sampling should be avoided because reliable separation from melanoma requires visualization of the entire lesion to allow for examination of architectural histopathologic features and avoid sampling error.

Multiple Keratoacanthomas after a Recent Tattoo: A Case Report.

We report on a 39-year-old man who presented with seven skin lesions on the right thigh 3 weeks after receiving a large tattoo which included red and black pigments. Initially, the lesions grew fast, later their growth stabilized. Histopathology showed well-circumscribed symmetric tumors with a central keratin-filled crater along with further trademarks of a keratoacanthoma. The patient had previously had multiple tattoos with no history of similar lesions. PCR analysis of one of the lesions revealed the presence of human papillomavirus 6. All lesions were excised with a safety margin. A 3-month follow-up revealed no further lesions.

Vascular Endothelial Growth Factor Receptor-3 Expression Predicts Sentinel Node Status in Primary Cutaneous Melanoma.

This study analysed the expression of vascular endothelial growth factor-A (VEGF), VEGFR-2, and VEGFR-3 in primary cutaneous melanomas with positive and negative sentinel node status (SLN) (a total of 58 specimens divided into 2 groups of 29 for each status). The specimens were collected from the pathological archive of the department of Dermatology, Venereology and Allergology of the University Medical Center Heidelberg. A quantification score was developed for protein expression, by considering the percentage of positive melanoma cells (0: 0%, 1: up to 1%, 2: 2-10%, 3: 11-50%, and 4: > 50%) in relation to the intensity of staining (0: negative, 1: low, 2: medium, 3: strong). Tumoural VEGFR-3 expression (mean ± standard deviation) in SLN+ tumours (9.62 ± 3.09) was significantly stronger than in SLN- tumours (6.13 ± 3.87; p < 0.001). A binary logistic regression model proved VEGFR-3 expression and tumour thickness to be significant independent predictors of SLN. These data provide evidence that VEGFR-3 expression may play a critical role in the pathogenesis of malignant melanoma and that its investigation may help to improve the selection of patients with primary cutaneous melanoma for sentinel node biopsy.

Angiogenesis in Ocular and Extraocular Sebaceous Carcinoma.

To shed more light on the pathogenesis of sebaceous carcinoma, we analysed the expression of proteins related to angiogenesis in 18 ocular and 22 extraocular sebaceous carcinomas using a broad panel of immunohistochemical markers. To quantify the expression of D2-40, vascular endothelial growth factor, vascular endothelial growth factor receptor-2 and -3, we calculated a quantification score by considering the percentage of positive tumour cells (0=0%, 1=up to 1%, 2=2-10%, 3=11-50%, and 4=>50%) in relation to the staining intensity (0=negative, 1=low, 2=medium, and 3=strong). Additionally, lymphatic microvessel density in the D2-40 stained sections was counted. Vascular endothelial growth factor receptor-3 (quantification score 9.42 ± 2.94) was significantly more strongly expressed than vascular endothelial growth factor receptor-2 (quantification score 2.15 ± 2.42, p < 0.001). Furthermore, epidermal vascular endothelial growth factor expression was negatively correlated with the intratumoural lymphatic vessel density, and the ratio of small lymphatics to large lymphatics was much higher in intratumoural tissue than in paratumoural tissue and in intraindividual control tissue, suggesting a lymphangiogenetic potential of sebaceous carcinoma.

Glucagonoma-Associated Necrolytic Migratory Erythema: The Broad Spectrum of the Clinical and Histopathological Findings and Clues to the Diagnosis.

Necrolytic migratory erythema (NEM) is associated with glucagonoma, an endocrine malignancy of the pancreas. It is a rare and a likely underrecognized paraneoplastic dermatitis. A 38-year-old woman presented to our clinic with a 3-year history of reocurring pruritic skin rashes with increasing intensity. The skin lesions presented with active annular borders, central scaling, and postinflammatory hyperpigmentation, but also with erosions, pustules, and crusted lesions. Multiple skin biopsies were taken. The workup of the patient revealed a tumor localized in the head of the pancreas, and glucagon serum levels were elevated. Clues to the diagnosis of NEM were the waxing and waning of serpiginous erythemas with active borders localized on extremities, intertriginous areas, and face. On histopathology, dyskeratosis in all layers of the epidermis were an early feature of NEM, and long-standing lesions typically showed psoriasiform hyperplasia with pallor and necrosis of upper epidermal layers. Clinicians and histopathologists need to be aware of the wide spectrum of skin manifestations in glucagonoma. Early diagnosis of the tumor is crucial for patients.

Testicular choriocarcinoma with cutaneous metastasis in a 19-year-old man.

A 19-year-old man suffering from testicular choriocarcinoma presented to the dermatology department with a cutaneous metastasis on his head. This metastasis was the first sign of disease that led to medical consultation. Histopathology revealed cytotrophoblasts and syncytiotrophoblasts, the later expressing human chorionic gonadotropin antigen. Whole body computed tomography showed multiple metastases of the brain, lung, liver, bone, paraaortic lymph nodes and left uvea; the primary was found in the left testicle. Despite neurosurgical intervention and chemotherapy the patient died 9 days after the biopsy of the cutaneous metastasis. Cutaneous metastases of testicular choriocarcinoma are exceptionally rare, with fewer than a dozen cases reported in the English-language literature. The present case highlights that testicular choriocarcinoma metastatic to the skin should be included in the differential of cutaneous scalp tumors.