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Erworbene Lymphgefastumoren sind selten. Das progressive Lymphangiom tritt ublicherweise als kleinere, meist umschriebene Plaque auf und ist durch eine langsame Grosenzunahme gekennzeichnet. Bei dem vorgestellten 13-jahrigen Jungen zeigte sich hingegen eine sehr ausgedehnte singulare Veranderung mit klinisch starkerer Induration ohne extrakutane Beteiligung. Die eingeleitete Systemtherapie mit Kortikosteroiden und Methotrexat zeigte eine Befundverbesserung. In Abhangigkeit vom Erscheinungsbild und der Beschwerdesymptomatik kann bei vergleichbaren Befunden auch eine Therapie mit mTOR-Inhibitoren diskutiert werden.

Syphilis, caused by the bacteria Treponema pallidum subspecies pallidum, is an infectious disease transmitted through direct, most frequently sexual, contact with infected mucosal lesions. In the last two decades the numbers of cases reported to the Robert Koch Institute (RKI) increased from around 2000 cases in 2000 to 7889 cases in 20191 . Syphilis is much more common in men than in women. In 2018, only 6.1% of the reported cases in Germany and 14% in the USA were female patients1,2 .

Basal cell carcinoma (BCC) is the most common malignant tumor among fair-skinned individuals, and its incidence had been steadily rising in the past decades. In order to maintain the highest quality of patient care possible, the German S2k guidelines were updated following a systematic literature search and with the participation of all professional societies and associations involved in the management of the disease. Part 2 addresses issues such as proper risk stratification, the various therapeutic approaches, and prevention as well as follow-up of patients with basal cell carcinoma.

Acquired tumors of lymphatic vessels are rare. Clinically, progressive lymphangioma usually appears as circumscribed plaques of small to medium size. In contrast, our case of a 13-year-old boy demonstrates a case of progressive lymphangioma with a solitary large indurated plaque. No extracutaneous manifestation was found. Systemic therapy with corticosteroids and methotrexate resulted in an improvement of the patient's condition. Dependent on clinical course and appearance of the disease, therapy with mTOR inhibitors may be considered as a therapeutic option.Erworbene Lymphgefäßtumoren sind selten. Das progressive Lymphangiom tritt üblicherweise als kleinere, meist umschriebene Plaque auf und ist durch eine langsame Größenzunahme gekennzeichnet. Bei dem vorgestellten 13-jährigen Jungen zeigte sich hingegen eine sehr ausgedehnte singuläre Veränderung mit klinisch stärkerer Induration ohne extrakutane Beteiligung. Die eingeleitete Systemtherapie mit Kortikosteroiden und Methotrexat zeigte eine Befundverbesserung. In Abhängigkeit vom Erscheinungsbild und der Beschwerdesymptomatik kann bei vergleichbaren Befunden auch eine Therapie mit mTOR-Inhibitoren diskutiert werden.

Basal cell carcinoma is the most common malignant tumor among fair-skinned individuals, and its incidence has been rising steadily in the past decades. In order to maintain the highest quality of patient care possible, the German S2k guidelines were updated following a systematic literature search and with the participation of all professional societies and associations involved in the management of the disease. Part 1 highlights new developments in genetics in particular as well as aspects regarding epidemiology, diagnosis, and histology.

BACKGROUND: Kaposi’s sarcoma was first described in 1872 by Moritz Kaposi. To date, it is considered a malignant disease is originating from the endothelial cells of the lymphatic vessels believed to be infected with HHV-8. The current classification defines four major epidemiological forms of Kaposi’s sarcoma: classical, endemic, AIDS-associated, and iatrogenic. CASE REPORT: A 90-year-old male is presented with multiple plaques- and tumour-shaped brown-violet formations located on an erythematous-livid base in the area of both feet and both shanks. Two samples were taken from the lesions on the skin of the shanks, with histopathological examination and the subsequent immunohistochemistry showing Kaposi’s sarcoma. CONCLUSIONS: Kaposi sarcoma is a disease that causes difficulties both in diagnostic and therapeutic respect. The only sure way to determine the correct diagnosis is immunohistochemical staining with the anti-HHV8 antibody. Despite the wide range of systematic and local treatment options, there is still no unified algorithm and a unified strategy for the treatment of Kaposi’s sarcoma.

Background We investigated 2 cases of deceptively bland cutaneous angiosarcoma (AS), which showed a uniform clinical presentation with a rapidly growing tumor on the nose. It remains unclear whether this was a primary cutaneous manifestation or a metastasis. Both tumors initially presented a high histologic overlap with a benign vascular tumor. The diagnosis was primarily based on the rapidly progressing clinical course and on the results of the staging procedures. Methods Immunohistochemical stains were performed for cytokeratin (AE1/AE3 and MNF116), CD31, ERG, CD34 (HPCA1/my10), D2-40/podoplanin, LYVE-1, Ki67, PHH3, αSMA (1A4), MYC, FOS-B, CAMTA-1, TFE-3, WT1, nestin, VEGFR-2(KDR), VEGFR-3(FLT4), HHV8. MYC amplification was also investigated by fluorescence in situ hybridization. Results The tumor cells were negative for MYC and revealed no D2-40/podoplanin expression. SMA-positive pericytes formed rims around the vessel. The proliferative activity (Ki-67) was elevated, in one case only in a later stage. Discussion Cutaneous ASs can be rather bland and may easily be mistaken for benign vascular tumors. Both cases presented a uniform clinical picture, which implied a malignant vascular tumor. In contrast, the cytomorphology of the endothelial cells and the immunohistochemical profile were not suspicious. We worked out subtle histological criteria, which should allow an early detection of such tumors.

Die elastischen Fasern sind neben den kollagenen Fasern der wichtigste Bestandteil des Bindegewebsgerustes der Haut. Eine Verminderung oder ein Verlust der elastischen Fasern ist bei einer Vielzahl von klinisch sich unterschiedlich prasentierenden Erkrankungen, hereditar oder erworben, beschrieben. Bei den Erkrankungen, die mit einer Entzundung einhergehen ist die Elastophagozytose ein wichtiges histologisches Merkmal. Die Therapie der Erkrankungen dieser Gruppe ist grundsatzlich schwierig.

Along with collagen, elastic fibers are integral components of cutaneous connective tissue. A decrease in elastic fibers or loss thereof has been described in a number of clinically distinct skin diseases, both hereditary and acquired. In disorders associated with inflammation, elastophagocytosis is an important histological hallmark. Treatment is generally difficult.

BACKGROUND: Merkel cell carcinoma (MCC) is an aggressive neoplasm, which is often associated with Merkel cell polyomavirus (MCPyV). Programmed death-1 (PD-1) and its ligand PD-L1 are key players of the tumor microenvironment (TME). METHODS: Fourteen paraffin-embedded tissue samples of MCC were stratified by their MCPyV detection. Apart from PD-L1 and PD-1, the TME was further characterized for the expression of CD33, FOXP3 and MxA. RESULTS: We observed PD-1 in 2 of 12 tumors. PD-L1 expression by tumor cells was found in 7 of 8 MCPyV(+) samples and was detected particularly in the periphery. The tumor cells were surrounded by a shield of PD-L1/CD33 immune cells. Expression of PD-L1 by the tumor cells was higher in areas with a denser immune infiltrate. CD33(+) cells without direct tumor contact were PD-L1 negative. Only a low number of FOXP3(+) regulatory T-cells was admixed. Tumor cells of MCPyV(-) samples were mostly PD-L1 negative. CONCLUSIONS: Our data demonstrate that PD-L1 expression occurs in tumor and immune cells, in areas in which they are close in contact. Interferon seems to play a role in this interaction. We postulate that PD-L1(+)/CD33(+) cells shield the tumor against attacking PD-1(+) immune cells. Therefore, next to anti-PD-1/PD-L1 antibodies, blockade of CD33 seems to be a promising therapeutic approach.

BACKGROUND: The Stewart-Treves syndrome with localisation in the region of the lower extremities is not something unusual as clinical pathology, but the clinical diagnostics is rather difficult, and it can be further complicated maximally because of: the similar locoregional findings in patients with other cutaneous malignancies.CASE REPORT: Presented is a rare form of an epithelioid variant of the Stewart Treves syndrome in a woman, aged 81, localised in the region of the lower leg and significantly advanced only for 2 months. The diagnosis was confirmed histologically and immunohistochemically. Amputation of the affected extremity was planned. Discussed are important etiopathogenetic aspects regarding the approach in patients with lymphedema and possibility for development of the Stewart Treves syndrome.CONCLUSION: Analyzing the evidence from the literature worldwide, we concluded that perhaps the only reliable (to some extent) therapeutic option in patients with Stewart Treves Syndrome is 1) the early diagnostics and 2) the following inevitable radical excision or amputation with the maximal field of surgical security in the proximal direction.

Background The immune checkpoint molecule PD‐L1 represents an important target in oncological immune therapy. The aim of our study was to evaluate PD‐L1 expression and the composition of the tumor microenvironment (TME) in Kaposi sarcoma. Methods Immunohistochemical stains were performed for PD‐L1, CD3, CD33, CD68, and CD168 in 24 Kaposi sarcoma samples. In PD‐L1‐positive cases, the double stains for PD‐L1, CD31, podoplanin, and HHV8 were added. Results PD‐L1 was observed in 71% of the samples and was predominantly located in the TME. PD‐L1 expression was significantly higher in nodular stage than in patch/plaque stage. The TME consisted of CD68+/CD163+ macrophages, CD33+ myloid‐derived suppressor cells and monocytes and CD3+ T‐cells. The TME showed a peritumoral distribution in nodular stage, in contrast to a diffuse distribution in patch/plaque stage. In 12 samples (50%), no plasma cells were found. Conclusion In nodular stage of KS, the TME is pushed back in the periphery of the tumor nodules. The PD‐L1‐positive TME between the tumor cells might protect them from the immune attack. An anti‐PD‐L1 treatment might be promising in KS patients.

Background In 2009, the AJCC issued a revised melanoma staging system. In addition to tumor thickness and ulceration, the mitotic rate was introduced as the third major prognostic parameter for the classification of primary cutaneous melanoma. Given that, according to the 2009 AJCC classification, the detection of one or more dermal tumor mitoses leads to an upstaging - from stage Ia to Ib - of melanomas with a tumor thickness of ≤ 1.0 mm, we set out to investigate the reproducibility of this new parameter. Methods In order to assess interobserver reliability, 17 dermatopathologists und pathologists - all well versed in the diagnosis of cutaneous melanoma - analyzed the mitotic rate in 15 thin primary cutaneous melanomas (mean tumor thickness 0.91 mm) using identical slides. Mitotic rates were determined on H&E and phosphohistone H3 (Ser10)-stained samples. Without knowledge of their previous assessment, five of the aforementioned examiners reevaluated the samples after more than one year in order to ascertain intraobserver reliability. Results Interobserver reliability of the mitotic rate in thin primary melanomas is disappointing and independent of whether H&E or immunohistochemically stained samples are used (kappa value: 0.088 [H&E], 0.154 [IH], respectively). Kappa values improved to 0.345 (H&E) and 0.403 (IH) when using a cutoff of 0/1 vs. 2+ mitoses. Similarly unsatisfactory, kappa values for intraobserver reliability ranged from 0.18 and 0.348, depending on the individual examiner. Discussion Given the unsatisfactory reproducibility and large variations in assessing the mitotic rate, it remains a matter of debate whether this diagnostic parameter should play a role in therapeutic decisions.

ZusammenfassungHintergrund Die Melanomklassifikation wurde 2009 durch die AJCC revidiert. Fur die Klassifizierung primarer Melanome wurde als dritte Grose neben Tumordicke und Ulzeration die Angabe der Mitoserate neu eingefuhrt. Gemas der AJCC-2009-Klassifikation des Melanoms fuhrt der Nachweis nur einer oder mehrerer dermaler Tumormitosen bei Melanomen ≤ 1,0 mm Tumordicke zu einer Umgruppierung des Tumors von T1a nach T1b. Dies erklart, wie wichtig die Frage nach der Reproduzierbarkeit dieses neuen Parameters ist. Methoden Zur Prufung der Interobserver-Reproduzierbarkeit der Mitoserate haben 17 Dermatopathologen und Pathologen, die in der Befundung des kutanen Melanoms sehr erfahren sind, die Mitoserate in 15 dunnen Melanomen mit einer mittleren Tumordicke von 0,91 mm an demselben Tumorschnitt bestimmt. Die Mitoserate wurde am HE-Schnitt und immunhistologisch (IH) mittels des mitosespezifischen Antikorpers Phospho-Histon-H3 (Ser10) bestimmt. Funf Befunder wiederholten die Bestimmung nach mehr als einem Jahr ohne Kenntnis ihres Vorbefundes zur Ermittlung der Intraobserver-Reproduzierbarkeit. Ergebnisse Die Interobserver-Reproduzierbarkeit der Mitoserate bei dunnen Melanomen ist unbefriedigend und unabhangig davon, ob die Mitoserate am HE-Schnitt oder am immungefarbten Schnitt bestimmt wird (κ-Werte: 0,088 [HE] bzw. 0,154 [IH]). Bei einer Diskriminationsschwelle von 0/1 vs. 2+ Mitosen verbesserte sich der κ-Wert auf 0,345 (HE) bzw. 0,403 (IH). Die Intraobserver-Reproduzierbarkeit lag mit κ-Werten zwischen 0,18 und 0,348 je nach Befunder ebenfalls im unbefriedigenden Bereich. Diskussion Wegen der unbefriedigenden Reproduzierbarkeit und der grosen Variation der Befunde zur Mitoserate bleibt es zweifelhaft, ob dieser Befund als Grundlage fur Therapieentscheidungen herangezogen werden kann.

Granulomatous disorders affecting the skin belong to a heterogeneous group of diseases, which were predominantly classified based on pathogenetic features. In infections diseases a granuloma is formed if an agent could not be eliminated by the immune system. Typical agents which cause granulomatous reactions are mycobacteria, fungal infections, especially extra European agent, which could effect the skin by, dissemination (e.g. histoplasmosis) or parasites, like leishmaniasis.

Zusammenfassung Granulomatose Hauterkrankungen gehoren einer heterogenen Gruppe an, die zumeist aufgrund ihrer Pathogenese klassifiziert werden. Im Rahmen von Infektionen treten Granulome insbesondere dann auf, wenn der Erreger durch das Immunsystem schlecht zu eliminieren ist. Klassische Vertreter auf der Seite der Bakterien sind die Mykobakterien, bei den Pilzen finden sich insbesondere extraeuropaische Erreger, die zum Teil durch Dissemination das Hautorgan befallen (z. B. Histoplasmose) sowie die Leishmanien aus der Gruppe der Parasiten.

Bei einer symmetrisch ausgebildeten Dystrophie der Groszehen muss die kongenitale Groszehennageldystrophie beziehungsweise die Spatmanifestation in der Adoleszenz bedacht werden. Fur die Spatmanifestation gibt es die Bezeichnung „Pfeilschwanzkrebs-Onychodystrophie“, die sich jedoch noch nicht durchgesetzt hat.

BACKGROUND: Keratinocyte cancers are malignant diseases with a broad incidence of spread which tends to increase during the last couple of decades. The solar radiation plays a dominant role in the occurrence of BCC, but certain genetic phenotypes appear to be risky from an etiological point of view. Metatypical basal cell carcinoma (MTBCC) is a rare variant of BCC which combines the clinical and histological characteristics of BCC and SCC. Clinically they are indistinguishable from the conventional BCC, and only the histological examination can differentiate them. The MTBCC is a histological subtype which is considered more aggressive due to its ability to produce local recurrences or distant metastases.CASE REPORT: We present a 44-year old patient with multiple BCCs disseminated on the face and body. The biopsy established mixed type histology: three metatypical and four solid BCCs. The lesions were removed via elliptical excision with a field of operational security of 0.5 cm in all directions.CONCLUSIONS: The eruptive (multiple) BCCs are a challenge about the choice of a therapy option. This is because clinically completely identical tumours show different histopathological characteristics, namely those with a tendency to metastasise. Having in mind one of the hypotheses of metatypical BCC emergence - the improper or inadequate radiotherapy (as a choice of therapy) could trigger the transition of a conventional tumour to a metastasising one, the surgical treatment appears to be the most secure treatment method.

Melanotische Flecke sind durch eine umschriebene Vermehrung von Melaninpigment charakterisiert, die Anzahl der epidermalen Melanozyten ist aber weitgehend normal oder nur gering vermehrt. Aufgrund der klinischen Ahnlichkeit sowie der Differenzialdiagnose zu und der haufigen Uberlappung mit den melanozytaren Navi werden beide gemeinsam besprochen. Melanozytare Navi sind gutartige, umschriebene Proliferationen von Melanozyten in der Haut. Die Frage, ob es sich bei den melanozytaren Navi um genetisch determinierte Fehlbildungen (Hamartome) oder um benigne Tumoren der Melanozyten handelt, ist nicht einheitlich zu beantworten. So ist bei einem grosen kongenitalen melanozytaren Navus eher von einem Hamartom auszugehen, wahrend ein unter UV-Strahlung erworbener, sich in der Pubertat manifestierender melanozytarer Navus eher im Sinne einer benignen Neoplasie der Melanozyten interpretiert werden kann. Im klinischen Alltag sind die benignen Pigmenttumoren vor allem wegen der Abgrenzung zum Melanom bedeutsam.

The mitotic rate is an important prognostic criterion in patients with thin melanoma ≤ 1 mm.The aim of this study was to investigate the reproducibility of the mitotic rate in thin melanoma in hematoxylin-eosin (HE) stain and compare it with the detection of mitotic figures by immunohistochemistry.The number of mitoses stated in the routine diagnostic report in 190 pT1 melanomas was compared with the number gained from re-evaluation of HE sections and the number detected after staining with the mitotic marker, phosphohistone H3 (PHH3). Two different approaches were used for choosing the "hot spot" for evaluation (dermal vs epidermal/dermal).Comparing routine HE-stained slides with re-evaluation slides, the number of mitotic figures was slightly variable. However, findings did not result in a change of the tumor stage. In 34% of the tumors with dermal mitotic figures on HE, mitoses could not be found in the corresponding PHH3 slide anymore. In 4% of the cases, stage relevant mitoses could only be found by PHH3 immunohistochemistry.This is a single center study.Immunohistochemical staining for mitotic figures does not replace a careful evaluation of HE-stained slides. Immunohistochemical detection of mitosis is only an additional tool; the time-saving effect is therefore negligible.

Background Lymphoplasmacytic plaque (LPP) is a recently described rare skin disease characterized by a dense dermal lymphohistiocytic infiltrate with polyclonal plasma cells. The clinical picture is distinct with reddish to brownish plaque with a predilection for the lower leg. LPP typically affects children. Objective To define clinical and histologic criteria of LPP and to develop a diagnostic flow chart. Methods We investigated six of our own LPP cases. Immunoglobulin light chains, IgG, IgG4, CD31, CD163 as a histiocytic marker were examined by immunohistochemistry. PCR-based molecular studies were conducted for borrelia sp., mycobacterial and leishmania sp. Moreover, 10 cases, which have been reported in the literature, were checked for the same features. Results We could differentiate three main histological patterns (superficial band-like only, [deep] dermal only and mixed). Acanthosis and interface dermatitis are key features in cases with a superficial band-like or mixed infiltrate. Granulomas and giant cells could be only found in about 30% of the cases. The number of plasma cells was variable accounting for 5–40% of the infiltrate. The number of blood vessels was increased in the majority of the cases. ‘Free-floating’ collagen bundles surrounded by histiocytes (pseudorosettes) were identified as a new histological feature. An infectious agent could be excluded in all cases. Conclusions LPP is a long-standing skin disease, which may also occur in adults and in other body regions than the lower leg. Reproducible clinical and histological criteria allow delineating a diagnostic work-up for LPP.

Granulomatous disorders affecting the skin belong to a heterogeneous group of diseases. With the exception of granulomas induced by infectious agents or foreign bodies, the etiopathogenesis of granulomatous disorders is still poorly understood. The knowledge of histopathologic changes is of great importance for understanding clinical presentation and disease course.

Background: In nodal anaplastic large cell lymphoma, strong expression of galectin-3 (Gal-3) has been found, but only very few cases of primary cutaneous lymphoma have so far been examined. Objectives: To investigate 11 primary cutaneous anaplastic large cell lymphomas (PCALCL), 47 lymphomatoid papuloses (LYP) and 14 cases of transformed mycosis fungoides with CD30 expression (MF-T) for Gal-3 expression. Methods: A Gal-3 score was applied using a photo-based morphometric evaluation program. Double staining for CD30 and Gal-3 was performed. Furthermore, we recorded the cellular and extracellular sublocalization of the signal. Results: The Gal-3 expression in CD30+ tumor cells was significantly lower in MF-T in contrast to CD30+ lymphoproliferative disorders (CD30 LPD; p < 0.001), but we found no differences between PCALCL and LYP (p = 0.42). In PCALCL Gal-3 was more often localized in the cytoplasm in contrast to LYP, in which an equal distribution in the cytoplasm and the nucleus was more common (p = 0.9). Conclusions: The lower Gal-3 expression in MF-T in comparison to CD30 LPD might be an additional criterion to differentiate both entities. The different sublocalization of the Gal-3 signal might reflect a different biological function and behavior.