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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., (© 2022. The Author(s).)

We report the case of a 12-year-old girl with a smooth muscle hamartoma of the right index finger. Smooth muscle hamartoma (SMH) is a congenital, relatively common disorder typically with predominance of autochthonal arrector pili muscles. An SMH can also rarely originate from smooth muscles of vessels in palmoplantar skin with the absence of pilosebaceous units. Because of overlapping histological features, the possibility of Becker's nevus being identical or associated with SMH has often been suspected by some authors.

Clinicopathologic correlation is the basis of a precise diagnosis. Especially in dermatopathology, the precision of a microscopic diagnosis may significantly be increased by thorough knowledge of the clinical picture. The advent of digital photography, the internet and moderately priced CDs and USB-sticks have made it possible to establish and maintain a time-saving, low-cost picture data transfer between dermatologist and dermatopathologist which is optimally suited for clinicopathologic correlation.

Circumscribed acral hypokeratosis is a rare chronic disorder of cornification that occurs predominantly in women. Lesions are solitary and do not respond to any local conservative treatment. They have to be differentiated by biopsy from other non-healing lesions and tumors in acral skin. Clinically lesions appear as sharply circumscribed reddish macules. The histologic hallmark is a circumscribed loss of the entire stratum corneum, which can be best demonstrated at the border of the lesion as a contrast to the perilesional broad stratum corneum typical for acral sites.

Background and Objective: Invasion of squamous cell carcinoma of the head and neck into cutaneous nerves is rare and can easily be missed. Perineural outgrowth into cerebral nerves may result in severe pain or neurological disturbances. In addition, these carcinomas more often recur or metastasize and therefore are associated with a poor prognosis., Patients/methods: We report on two patients with squamous cell carcinoma of the dorsum of the nose and lower lip exhibiting neurotropic growth., Results: Histology showed pleomorphic keratinocytes growing deep into the subcutaneous tissue and bone, respectively. The presence of few pleomorphic keratinocytes could be only confirmed by immunohistochemistry, though indicated by a perineural lymphocytic infiltrate. In both patients, several re-excisions were necessary to achieve cure., Conclusions: In neurotropic squamous cell carcinoma a consequent radical micrographic surgery as well as neurological and radiological investigations are mandatory. We also review the literature.

Diffuse dermal angiomatosis (DDA) is a benign, acquired vascular proliferation characterized by painful, poorly circumscribed, livid-erythematous plaques with frequent central ulceration. The clinical features are reminiscent of reactive angioendotheliomatosis or embolia cutis medicamentosa. Histologically, a dense diffuse network of regular capillary vessels throughout the dermis is seen. Endothelial atypia, atypical mitoses or signs of vasculitis are missing. A 43-year-old woman developed a bizarre brownish-livid rapidly growing lesion of DDA 8 centimeters above a surgical scar, shortly after removal of 20 kilograms of fatty tissue from the lower abdominal wall. DDA regressed spontaneously within 12 weeks, and has not recurred over 4 years of follow-up.

Background and Objective: Endothelial nuclear atypia is the hallmark of malignant vascular tumors. Pleomorphic nuclei of the muscular vessel wall and the adventitia are manifestations of degenerative phenomena and should not be misinterpreted as signs of malignancy., Patients/methods: Three long-standing solitary superficial vascular tumors (61-year-old woman, 48- and 63-year-old men) were removed by primary excision. Sections were stained according to standard histologic and immunohistologic protocols., Results: Symplastic hemangiomas show the silhouette of a small superficial angioleiomyoma or capillary hemangioma. Characteristic features are multinucleate cells of the muscular vessel wall and the adventitia with pleomorphic nuclei, broad hyalinized vessel walls, and the distinctive lack of endothelial nuclear atypia. Recurrences or metastases were not reported (follow-up of 9, 45 and 90 months)., Conclusions: Symplastic hemangioma is a benign superficial hemangioma with histological features of a pseudomalignancy. The distinctive lack of endothelial nuclear atypia allows distinction from malignant vascular tumors.

Clinical and histopathological findings of 34 cases of desmoplastic malignant melanoma (DMM) are summarized and compared to the literature. DMM develop mostly in sun damaged skin of elderly patients, they are rare and often nonpigmented tumors that are difficult to diagnose clinically. In all cases the tumor parameters showed level IV or V melanomas (level IV: 55.9%, level IV-V: 14.7%, level V: 29.4%) and the tumor thickness measured 3.85 mm +/- 2.31 mm (1.0-11.0 mm). In 22 cases, the follow-up time was between 2 and 7 years. Local recurrences were observed in 7 ( = 31.8%) patients, metastases in 4 ( = 18.2%) and tumor-related deaths in 3. The prognosis for our patients seems to be slightly better than that described in the literature. The main reason is an improved histological diagnosis of this special type of melanoma. Using immunohistochemical staining with anti-S100 antibody it is possible to establish the melanocytic nature of these fibrotic spindle cell tumors earlier that is, in small initial biopsies, and tumor margins can be defined more accurately. As a consequence, surgery is done earlier and is more likely to be curative.

Two female and three male patients with acquired "tufted angioma" are presented. The age of these patients ranged from 10 to 62 years. Two lesions were sited in the head and neck region, two in the upper extremities, and one on the trunk. Clinically, the angiomatous lesions appeared as elevated plaques, flat lesions with papular and macular areas, or erythematous plaques with small nodules. In four cases a biopsy was done, and in one case the tumour was excised. Histologically, the neoplasms were characterized by irregularly distributed vascular tufts in the dermis, and, in one case, in the upper subcutis. The vascular tufts were composed of plump endothelial cells and spindle-shaped pericytes surrounded by crescent-shaped vascular spaces. The positive staining for CD 31 and for CD 34 and alpha-smooth muscle actin, and the negative staining of endothelial cells for factor VIII underline both the existence of two cellular components in tufted angioma and the immaturity of endothelial cells. Evidence of regular mitotic figures in two cases and increased proliferative activity in three out of four cases tested, emphasize the neoplastic nature of slowly growing tufted angioma. Benign tufted angioma is a distinct entity in the spectrum of capillary haemangiomas and must be distinguished from other vascular neoplasms.

On the basis of two cases the differences between the plaque-like variant of dermatofibrosarcoma protuberans (PDFSP) and the plaque-like dermal fibromatosis (synonym: dermatomyofibroma; PDF) are presented. PDFSP and PDF are two clinically very similar dermal fibrous proliferations, but differentiation is important because of their different therapy and prognosis. Histologically and immunohistochemically PDFSP and PDF can be recognized as separate entities.

Adult myofibroma is an acquired skin tumour that is histologically identical to infantile myofibroma. Histologically, four tumour variants can be distinguished: leiomyoma type, cellular spindle cell type, haemangiopericytoma or glomus type, and biphasic type. Practical help in diagnosis is supplied by the hamartomatous composition of the leiomyoma-type, hyalinized spindle cell whorls, endothelium-lined haemangiopericytoma-like vascular channels, and desmin-negative, muscle-actin-positive myofibroblasts, which may show spindle cell or undifferentiated mesenchymal cell differentiation. The tumours clinically present as firm, occasionally bluish cutaneous or subcutaneous nodules. Adult myofibroma should be recognized as a distinct benign neoplasm, most probably of vascular origin. Clinicians and dermatopathologists must be aware that lesions identical to those of infantile myofibroma can occur in adults.

Pigmented epidermotropic breast carcinoma has to be included in the differential diagnosis of pigmented lesions of the breast. Two rare cases of pigmented Paget's disease and pigmented metastatic breast carcinoma are presented, which mimicked malignant melanoma in both clinical and histological criteria.

Lymphoepithelioma-like carcinoma of the skin (LECS) is a rare cutaneous tumour with histological features resembling those of Epstein-Barr virus-induced nasopharyngeal carcinoma. An LECS tumour may mimic lymphoid follicles in its composition. Its distinct histological pattern, however, is based on syncytial nests and cords of large pale-staining epithelial tumour cells surrounded by a dense lymphoplasmacytic infiltrate. Tumour cells show conspicuous vesicular nuclei with delicate chromatin and few prominent nucleoli. Histological differential diagnosis must include malignant lymphomas, Merkel cell tumour, squamous cell carcinoma and cutaneous metastasis of lymphoepithelioma. Immunostaining with anticytokeratin antibodies is highly significant in the differential diagnosis. Histological and immunohistological findings in an LECS removed from the upper lip of a 56-year-old women are reported. Serologic investigations did not indicate EBV-associated tumour growth.

Angioendotheliomatosis proliferans systemisata (AEPS) is a rare disease entity characterized by a predominantly intravascular proliferation of tumour cells. Two forms of AEPS are differentiated: a very rare, benign and self-limiting form, which is endothelial in origin, and a more common, malignant form, which is an angiotropic intravascular malignant B-cell lymphoma. Histological and immunohistological investigations of the malignant form of AEPS are presented: In a 69-year-old woman cutaneous lesions appeared 5 months before the diagnosis of B-immunoblastic lymphoma. In a 57-year-old woman lesions were observed simultaneously with the relapse of a high-grade malignant B-cell lymphoma. Immunohistological identification of the proliferating cell type made diagnosis of intravascular B-cell lymphoma possible in paraffin-embedded biopsies.

Solitary encapsulated neuroma (EN) is a true neuroma that is seldom diagnosed clinically. EN is the most frequently excised benign neuroma of the skin and has to be included in the differential diagnosis of small nodular facial tumours of middle-aged people. We report histological studies of 79 EN. EN are distinctive true neuromas that can easily be distinguished from all other benign neural neoplasms except the neuromas in the multiple mucosal neuroma syndrome.

The adamantinoid basal cell epithelioma is a clinically uncharacteristic but histologically typical variant of basal cell epithelioma characterized by a meshwork of stellate tumor cells.

Among a total of 270,000 skin biopsies, 87 desmoplastic trichoepitheliomas were identified, 11 (12.6%) of which were associated with nevocytic nevi. Histopathologically we found nevocytes next to horn cysts and thin strands of monomorphous basaloid neoplastic cells in a dense desmoplastic stroma. The frequency of this association suggests that it may be a combined malformation rather than a chance occurrence. On clinical examination most cases had been misdiagnosed as basal cell carcinomas. Most biopsies were taken from the faces of fairly young women.

Palmar and finger varicosis is a common abnormality of the veins in the elderly. This often overlooked age-related condition is illustrated by three observations.

After microwave irradiation with simultaneous field anesthesia, acute ulceration was observed. The danger of this complication following irradiation of areas with reduced sensitivity is stressed.

The peroxidase-antiperoxidase (PAP) technique allows the detection of immunoglobulin deposits in formalin-fixed, paraffin-embedded tissue. The PAP technique may be used as an alternative to the direct immunofluorescence method on frozen, unfixed skin. In addition, the PAP technique is suitable for retrospective evaluation of histological samples.

A 54-year-old male had erythema chronicum migrans (ECM), lymphocytic meningitis, and intense pain radiating along the distribution of the corresponding dermatomal segments. Neurologic involvement, described as Bannwarth syndrome or meningopolyneuritis Garin-Bujadoux-Bannwarth, is a typical late manifestation of ECM infection and requires high-dose intravenous penicillin therapy.