BACKGROUND AND OBJECTIVES:Tumor of follicular infundibulum (TFI) has been described as a neoplasm - isolated and multiple - and in association with other lesions. Its histopathologic definition is controversial. PATIENTS AND METHODS:We present a histopathologically analyzed series of 28 patients with TFI features. This has been supplemented by a search in MEDLINE on the literature on this subject. The corresponding figures given in these articles have been discussed and analyzed. RESULTS:Patients comprised 16 women and twelve men. TFI features were seen in five patients with nevus sebaceous, two trichofolliculomas, one dilated pore Winer, eight viral warts, one dermatofibroma, six seborrheic keratoses, three actinic keratoses, one invasive squamous cell carcinoma, and one basal cell carcinoma in association with a squamous cell carcinoma/actinic keratosis. After study of the literature especially of solitary cases of TFI, we interpret such cases mostly as variants of seborrheic keratoses with variable degree of infundibular, isthmic and/or sebaceous differentiation with or without regression. CONCLUSIONS:We regard TFI as an epithelial growth pattern which may occur in hamartomatous, inflammatory, infectious, reactive, or neoplastic conditions, in most solitary forms likely best classified within the histopathological spectrum of seborrheic keratoses.

ZusammenfassungHintergrund und ZieleDer Tumor des follikulären Infundibulums (TFI) wurde als Neoplasie – isoliert und multipel – und in Assoziation mit anderen epithelialen Läsionen beschrieben. Seine endgültige histopathologische Definition wird kontrovers diskutiert.Patienten und MethodikWir präsentieren eine retrospektive Serie von 28 Patienten mit TFI beziehungsweise TFI‐ähnlichen Veränderungen. Ergänzend wurde die in MEDLINE aufgeführte Literatur zum Thema TFI recherchiert und die darin publizierten Abbildungen interaktiv diskutiert und analysiert.ErgebnisseUnsere Patienten waren 16 Frauen und 12 Männer. TFI‐ähnliche Veränderungen fanden sich bei fünf Patienten mit Nävus sebaceus, zwei Trichofollikulomen, einer erweiterten Pore Winer, acht Virusakanthomen, einem Dermatofibrom, sechs seborrhoischen Keratosen, drei aktinischen Keratosen, einem invasiven Plattenepithelkarzinom und einem Basalzellkarzinom in Kombination mit Plattenepithelkarzinom/aktinischer Keratose. Nach Sichtung der Literatur, insbesondere von solitären Fällen von TFI, betrachten wir diese größtenteils als Variante von seborrhoischen Keratosen mit variablem Ausmaß von infundibulärer, isthmischer und/oder sebazärer Differenzierung mit oder ohne Regression.SchlussfolgerungenWir werten TFI insgesamt als ein epitheliales Wachstumsmuster, das bei hamartomatösen, entzündlichen inkludierend infektiösen, reaktiven oder neoplastischen Prozessen auftreten und in den meisten solitären Formen am ehesten innerhalb des histologischen Spektrums seborrhoischer Keratosen eingeordnet werden kann.

In this review, we propose a classification of vasculitides and occluding vasculopathies using the clinicopathological correlation as the basic process. We use an algorithmic approach with pattern analysis, which allows reliable reporting of microscopic findings. We first differentiate between small and medium vessel vasculitis. Second, we differentiate the subtypes of small- and medium-sized vessels. Finally, we differentiate vasculitides according to the predominant cell type into leukocytoclastic and/or granulomatous vasculitis. Regarding leukocytoclastic vasculitis as a central reaction pattern of cutaneous small/medium vessel vasculitides, its relation or variations may be arranged in a wheel-like order. With respect to occluding vasculopathies, the first two steps are identical to the algorithm of vasculitides, and we finally differentiate according to the time point of the coagulation/reorganization process and the involved inflammatory cells/stromal features. By visualizing the criteria in the style of bar codes, clinical and histological overlaps and differences may become more transparent.

The globally increasing incidence of cutaneous malignancies leads, in parallel, to increasing numbers of locally advanced skin cancer resulting in reconstructive surgery. Reasons for locally advanced skin cancer may be a patient’s neglect or aggressive tumor growth, such as desmoplastic growth or perineural invasion. This study investigates characteristics of cutaneous malignancies requiring microsurgical reconstruction with the aim of identifying possible pitfalls and improving diagnostic and therapeutic processes. A retrospective data analysis from 2015 to 2020 was conducted. Seventeen patients (n = 17) were included. The mean age at reconstructive surgery was 68.5 (±13) years. The majority of patients (14/17, 82%) presented with recurrent skin cancer. The most common histological entity was squamous cell carcinoma (10/17, 59%). All neoplasms showed at least one of the following histopathological characteristics: desmoplastic growth (12/17, 71%), perineural invasion (6/17, 35%), or tumor thickness of at least 6 mm (9/17, 53%). The mean number of surgical resections until cancer-free resection margins (R0) were achieved was 2.4 (±0.7). The local recurrence rate and the rate of distant metastases were 36%. Identified high-risk neoplastic characteristics, such as desmoplastic growth, perineural invasion, and a tumor depth of at least 6 mm, require a more extensive surgical treatment without concerns about defect size.

Das Plattenepithelkarzinom ist nach dem Basalzellkarzinom das zweithäufigste Malignom der Haut und wird vorwiegend an sonnenexponierten Stellen wie der Gesichtshaut diagnostiziert. Diese meist lokal destruktiv wachsende Malignität kann durchaus auch invasives Wachstumsverhalten, wie perineurale Ausbreitungsmechanismen, aufweisen. Das Plattenepithelkarzinom der periorbitalen Region ist in bis zu 14 % der Fälle mit perineuraler Invasion assoziiert. Vor allem in diesem Bereich birgt die anatomische Nähe zu den Hirnnerven das Risiko einer Progression Richtung zentrales Nervensystem, was mit einer schlechteren Prognose assoziiert ist. Der klinisch unauffällige Charakter dieser Entität resultiert oft in einer Verzögerung der definitiven Diagnosestellung, wodurch die vollständige Resektion und anschließende Rekonstruktion erschwert werden. Eine aufmerksame klinische Evaluierung kann bereits vor Erlangen histologischer Befunde Hinweise für ein perineurales Wachstum liefern. Neben fünf herausfordernden Fällen analysiert diese Arbeit Risikofaktoren, klinische als auch histologische Merkmale und Behandlungsoptionen des periorbitalen Plattenepithelkarzinoms mit perineuraler Invasion.

INTRODUCTION:Sarcoidosis is a systemic granulomatous disease with a variable clinical presentation and disease course. There is still no reliable biomarker available, which assists in the diagnosis or prediction of the clinical course. According to a murine model, the expression level of the metabolic checkpoint kinase mechanistic target of Rapamycin complex 1 (mTORC1) in granulomas of sarcoidosis patients may be used as a clinical biomarker.MATERIAL AND METHODS:This is a retrospective analysis of 58 patients with histologically confirmed sarcoidosis. Immunohistochemical staining of granulomas from tissue samples was evaluated for the expression of activated mTORC1 signaling, including phosphorylated mTOR, its downstream effectors S6K1, 4EBP1 and the proliferation marker Ki-67. Patients were categorized according to different clinical phenotypes, serum biomarkers, and immunomodulatory therapy.RESULTS:All patients showed activated mTORC1 signaling in granulomas, which correlated with its downstream effectors S6K1 and 4EBP1 but was not related to Ki-67 expression. The mTORC1 activity revealed an association neither to disease severity nor the necessity of treatment; however, p-mTOR inversely correlated with cumulative corticosteroid dosage.CONCLUSION:Our data confirm activation of the mTORC1 pathway in sarcoidosis, supporting the hypothesis that mTOR is a significant driver in granuloma formation. However, we could not find a relationship between the degree of mTOR activation and disease severity or the need for therapy.

New developments in instrumentation and data analysis have further improved the perspectives of hyperspectral imaging in clinical use. Thus, hyperspectral imaging can be considered as “Next Generation Imaging” for future clinical research. As a contactless, non-invasive method with short process times of just a few seconds, it quantifies predefined substance classes. Results of hyperspectral imaging may support the detection of carcinomas and the classification of different tissue structures as well as the assessment of tissue blood flow. Taken together, this method combines the principle of spectroscopy with imaging using conventional visual cameras. Compared to other optical imaging methods, hyperspectral imaging also analyses deeper layers of tissue.

Abstract: Seborrheic keratosis with sebaceous differentiation (SKSD) can sometimes raise uncertainty, confuse with other even malignant entities, and lead to overestimation of this harmless variant. Retrospective analysis of the cases diagnosed as SKSD and a search of the pertaining literature were conducted. Eight cases of SKSD were found. Histologically, these lesions show a flat to plate-like outgrowth of basaloid cells with solitary or clustered sebocytes at the bottom of the rete ridges and variable sebaceous ducts with luminal cuticula. The lesions differed in the outgrowth subpattern: flat/macular, acanthotic, or reticulated. No association was found with Muir–Torre syndrome, and no malignant transformation was seen in these lesions. Literature search revealed confusingly designated lesions that simply represented SKSD. SKSD can show several growth patterns as classic SK. This entity is either underreported or even underrecognized. This entity is benign; however, according to the literature, exclusion of an associating Muir–Torre syndrome should be warranted. The published literature about this lesion is confusing and inconsistent. We suggest the avoidance of confusing terminology and particularly the terminus epithelioma for such lesions.

The goal of this project is to identify any in-depth benefits and drawbacks in the diagnosis of amalgam tattoos and other pigmented intraoral lesions using hyperspectral imagery collected from amalgam tattoos, benign, and malignant melanocytic neoplasms. Software solutions capable of classifying pigmented lesions of the skin already exist, but conventional red, green and blue images may be reaching an upper limit in their performance. Emerging technologies, such as hyperspectral imaging (HSI) utilize more than a hundred, continuous data channels, while also collecting data in the infrared. A total of 18 paraffin-embedded human tissue specimens of dark pigmented intraoral lesions (including the lip) were analyzed using visible and near-infrared (VIS-NIR) hyperspectral imagery obtained from HE-stained histopathological slides. Transmittance data were collected between 450 and 900 nm using a snapshot camera mounted to a microscope with a halogen light source. VIS-NIR spectra collected from different specimens, such as melanocytic cells and other tissues (eg, epithelium), produced distinct and diagnostic spectra that were used to identify these materials in several regions of interest, making it possible to distinguish between intraoral amalgam tattoos (intramucosal metallic foreign bodies) and melanocytic lesions of the intraoral mucosa and the lip (each with P < .01 using the independent t test). HSI is presented as a diagnostic tool for the rapidly growing field of digital pathology. In this preliminary study, amalgam tattoos were reliably differentiated from melanocytic lesions of the oral cavity and the lip.

Squamous cell carcinoma is the second most common malignancy of the skin after basal cell carcinoma and mainly found in sun‐exposed areas such as the face. This mostly locally destructive malignancy may show invasive growth and insidious mechanisms of dissemination such as perineural invasion. Periorbital squamous cell carcinoma is associated with perineural invasion in up to 14 % of cases. Specifically in this region, the proximity to cranial nerves and therefore the associated risk of progression to the central nervous system are associated with poor prognosis. The clinically concealed character of this entity often leads to a delay in diagnosis and consequently makes complete resection and reconstruction demanding. Careful clinical evaluation often hints at perineural invasion before obtaining histology.

Squamous cell carcinoma is the second most common malignancy of the skin after basal cell carcinoma and mainly found in sun-exposed areas such as the face. This mostly locally destructive malignancy may show invasive growth and insidious mechanisms of dissemination such as perineural invasion. Periorbital squamous cell carcinoma is associated with perineural invasion in up to 14 % of cases. Specifically in this region, the proximity to cranial nerves and therefore the associated risk of progression to the central nervous system are associated with poor prognosis. The clinically concealed character of this entity often leads to a delay in diagnosis and consequently makes complete resection and reconstruction demanding. Careful clinical evaluation often hints at perineural invasion before obtaining histology. Aside from presenting five challenging cases, this work analyzes risk factors, clinical as well as histological features, and treatment options for periorbital squamous cell carcinoma with perineural invasion.

Cutaneous vasculitides are inflammatory diseases starting at and evolving around the blood vessels of the skin. They should be separated from occluding vasculopathies, where the pathological process predominantely starts in the blood. They can be graded according to their relationship to systemic vasculitides as a cutaneous component of a systemic vasculitis, as a skin-dominant variant of a systemic vasculitis or as a cutaneous single organ vasculitis. Diagnostic measures, therapy and prognoses depend greatly on this relationship. For diagnostic purposes, a classification based on histopathological features in asscociation with clinicopathological correlation seems most reliable. We differentiate according to vessel size (small-medium-large) and involved cell types (leukocytes, macrophages) as well as extravascular features (necroses, granulomas). Thus, the similarities and overlaps between different manifestations become apparent.

Cutaneous melanoma (CM) incidence is rising worldwide and is the primary cause of death from skin disease in the Western world. Personal risk factors linked to environmental ultraviolet radiation (UVR) are well-known etiological factors contributing to its development. Nevertheless, UVR can contribute to the development of CM in different patterns and to varying degrees. The present study aimed at investigating whether altitude of residence can contribute to the development of specific types of CM and/or influence its progression. To this aim, 306 formalin-fixed and paraffin-embedded (FFPE) tissues from primary CM diagnosed in different geographical areas were submitted to B-RAF proto-oncogene serine/threonine kinase (BRAF) and N-RAS proto-oncogene GTPase (NRAS) mutational status detection and mRNA and miRNA profiling by qPCR. Genes were chosen for their functions in specific processes, such as immune response (CD2, PDL1, or CD274) and pigmentation (MITF, TYRP1, and TRPM1). Furthermore, four microRNAs, namely miR-150-5p, miR-155-5p, miR-204-5p, and miR-211-5p, were included in the profiling. Our results highlight differences in the gene expression profile of primary CM with respect to the geographical area and the altitude of residence. Melanoma-specific survival was influenced by the gene expression of mRNA and miRNAs and varied with the altitude of patients’ residence. In detail, TYRP1 and miR-204-5p were highly expressed in patients living at higher altitudes, unlike miR-150-5p, miR-155-5p, and miR-211-5p. Since miRNAs are highly regulated by reactive oxygen species, it is possible that different regulatory mechanisms characterize CMs at different altitudes due to the different environment and UVR intensity.

Erythema nodosum (EN) is considered to represent a septal panniculitis. In a period from January 2000 until June 2018, we clinically and histopathologically investigated 124 patients with EN, 13 (10.5%) of them in an early stage demonstrating features of a leukocytoclastic vasculitis (LCV) around postcapillary venules of the subcutaneous fat. Three of these patients presented with EN on the lower legs and Sweet syndrome on the head/neck, arms, or trunk. 19.3% and 70.2% of patients demonstrated “classic” features of subacute and chronic forms of EN, respectively. Histopathologically, in cases of early EN apart from septally accentuated vascular damage and neutrophils with nuclear dust, eosinophils were evident in 5 specimens as well, in one case even with flame figures as seen in Wells syndrome. The inflammation spilled over to the dermis and lobular panniculus in 12 and 10 specimens, respectively. From the same time period and for comparison, we investigated 497 cases of “classic” LCV. Depending on the degree of vascular damage and the presence of neutrophils and nuclear dust, 65.8% presented with acute, 18.9% with subacute, and 15.3% with late-stage disease. In the latter, only a few neutrophils but rather lymphocytes and macrophages were present. Four hundred forty patients revealed an involvement of the deep dermis; of those, in 342, a septal inflammation was present as well, whereas in 94, the process was purely dermal. The subcutis was missing for evaluation in 61 cases. These results indicate a closer relationship between EN and LCV than previously considered.

Background. Mechanical and thermal stress has been observed to trigger skin rejection in hand-transplanted patients. This study aims to investigate this phenomenon. Methods. Syngeneic and allogeneic orthotopic hindlimb transplantations were performed using male rats (Brown Norway to Lewis). Using a specially designed device, standardized mechanical skin irritation at a force of 5 N was applied to the planta pedis of the transplanted limb for 10 days, 4 times daily for 10 minutes. Biopsies, taken on day 10 and after a 5-day observational period, were assessed for macroscopic alterations using a standardized scale, by histopathology and immunohistochemistry, and for inflammatory protein expression using Luminex technology. Results. Allogeneic animals displayed significant aggravated macroscopic skin alterations compared with naive (P < 0.0001) and syngeneic controls (P = 0.0023). Histopathology showed a trend toward higher rejection/inflammation grades in allogeneic animals compared with syngeneic controls. Minor skin alterations in syngeneic limbs recovered quickly; however, in allogeneic limbs, macroscopic skin alterations were significantly more pronounced (P < 0.0001) 5 days after irritation. Interleukin-1b and interferon-γ levels were upregulated in skin of allogeneic limbs. Conclusions. Mechanical skin irritation in vascularized composite allotransplantation can trigger localized skin inflammation consistent with rejection.

Mesenchymale und neuronale Tumoren geben sich klinisch häufig nur schwer zu erkennen. Farbe, Lage und Tastbefund der Läsion sind zur differenzialdiagnostischen Abwägung hilfreich. Entsprechend der anatomischen Lokalisation mesenchymaler Strukturen wird zwischen Neoplasien des Bindegewebes und Fettgewebes, der glatten und quer gestreiften Muskulatur, des Knorpelgewebes und Knochengewebes sowie peripheren Nervensystems unterschieden. Für die präzise Einordnung dieser Läsionen ist eine repräsentative Gewebeentnahme mit dermatohistopathologischer Untersuchung häufig unerlässlich. Hierbei haben sich zahlreiche immunhistochemische Marker bewährt. Mit Einführung der Molekularbiologie sind bei vielen Entitäten Fluoreszenz-in-situ-Hybridisierung und Reverse-Transkriptase-Polymerase-Kettenreaktion zusätzlich diagnostisch hilfreich geworden. Darüber hinaus haben bei einigen malignen Neoplasien chromosomale Aberrationen prognostische und therapeutische Relevanz.