Leo Schärer

Angioinvasive lymphomatoid papulosis: a new variant simulating aggressive lymphomas.

Lymphomatoid papulosis (LyP) belongs to the spectrum of primary cutaneous CD30-positive lymphoproliferative disorders. Clinically, LyP is characterized by a variable number of self-healing papulo-nodular lesions, with the typical waxing and waning course. Histologically, 4 types (A, B, C, and D) have been delineated. Angioinvasive growth and large ulcers are rare findings in LyP and simulate aggressive lymphoma. We retrospectively analyzed the clinicopathologic and molecular features of angioinvasive LyP in a series of 16 patients. This new form of LyP is characterized by oligolesional papules that rapidly ulcerate and evolve into large necrotic eschar-like lesions with a diameter of 1 to 4 cm and an angiocentric and angiodestructive infiltrate of small-sized to medium-sized atypical lymphocytes expressing CD30 and frequently CD8. As in other forms of LyP, the lesions underwent spontaneous regression after a few weeks. Recurrences were common, but the prognosis was excellent with no extracutaneous spread or disease-related deaths. Complete remission occurred in 9 of 16 patients (56%). This LyP variant should be distinguished from aggressive forms of angiocentric and angiodestructive and cytotoxic T-cell lymphomas. We propose the term LyP type E for this clinically and histologically unusual variant.

Intra-lesional low-dose interferon α2a therapy for primary cutaneous marginal zone B-cell lymphoma

Primary cutaneous marginal zone lymphomas (pcMZL) belong to the primary cutaneous B-cell lymphoma (pCBCL) group. They are characterized by their restriction to the skin and a high likelihood of recurrence after various treatment modalities. First-line therapy consists of surgery and radiotherapy. These therapies may not always be indicated in young patients or in patients with pCBCL located in the face, where surgery or radiotherapy may leave disfiguring scars or radioderma. Eight patients with pcMZL were treated with intra-lesional injections of 3 million units of recombinant IFNα2a three times per week. The patients either did not want to undergo or did not qualify for surgical excision or radiotherapy due to inappropriate localization or age. All patients experienced complete tumor regression after a mean of 8.5 weeks (range 3 – 20). Two patients relapsed 4 and 12 months after treatment, respectively, but tumor regression was repeated after additional cycles of intra-lesional IFNα2a. All other patients remained free of disease. Thus, intra-lesional IFNα2a may represent a valuable alternative to surgery and radiotherapy as first-line treatment of pcMZL.

Progression of cutaneous squamous cell carcinoma in immunosuppressed patients is associated with reduced CD123+ and FOXP3+ cells in the perineoplastic inflammatory infiltrate.

Aims:  Squamous cell carcinoma of the skin (SCC) increases dramatically in organ transplant recipients (OTRs). The aim was to determine whether qualitative and quantitative differences in perineoplastic inflammation in OTRs contribute to the increased carcinogenesis.

Immunosuppression affects CD4+ mRNA expression and induces Th2 dominance in the microenvironment of cutaneous squamous cell carcinoma in organ transplant recipients.

Squamous cell carcinoma (SCC) is the most frequent cancer in organ transplant recipients (OTRs). The immune system plays a major role in the fight against SCC, however, little is known about the local inflammatory response in SCC at all. We analyzed quantity and quality of the perineoplastic inflammatory SCC microenvironment in immunocompetent patients and immmunosuppressed OTRs. RNA expression profile of SCC patients was analyzed for 8 different sets of genes relating to Th1 versus Th2 response using Gene Set Enrichment Analysis. SCC from immunocompetent patients and OTRs were analyzed by real-time polymerase chain reactions for CD4, CD8, TBET, GATA-3, FOXP3, RORC, IFN-γ, IL-4, TGF-&bgr;, IL-10, and IL-17A mRNA expression. Immunohistochemistry was carried out in SCC for CD3, CD4, CD8, and FOXP3 expression. Considerable inflammation was seen in both patient groups. SCC in immunocompetent patients and OTRs was associated with a mixed Th1 and Th2 gene expression signature. CD4+ mRNA was diminished in immunosuppression. Skin adjacent to SCC in OTRs showed Th2 expression pattern as compared with immunocompetent patients. T-BET and IFN-γ mRNA expression were decreased in the OTR group. Although Th17-weighted inflammation was unchanged, IL-17A mRNA level was markedly decreased with immunosuppression. Regulatory T cells, characterized by FOX-P3 and TGF-β mRNA level, were decreased in OTRs. Our findings support the hypothesis that nontumor-bearing skin adjacent to SCC in OTRs is not necessarily normal and that the local microenvironment may contribute to a field effect contributing to higher recurrence rates and more aggressive behavior observed in these patients.

Cutaneous malignant lymphomas: Update 2006

Cutaneous lymphomas represent a unique group of lymphomas and are the second most frequent extranodal lymphomas. As with other neoplasias, the pathogenesis is based mainly on a stepwise accumulation of mutations of suppressor genes and oncogenes caused by genetic, environmental or infectious factors. The diagnostic work‐up includes clinical, histological, imaging and hematological investigations and in many cases immunohistochemical and molecular biological analyses.

Weight of decision-making impairs clinical assessment of melanocytic lesions.

Background and Objective: We studied the weight of decision-making on clinical assessment of melanocytic lesions judging benign, atypical, and malignant lesions; common mistakes; and total removal rates, comparing dermatologists with nondermatologists. Methods: Of 11,246 histopathology specimens, 3,768 had a clinical assessment of melanocytic lesions. Histopathologic diagnosis served as the gold standard. Results: Benign nevi were assessed most accurately (77%). Dermatologists assessed benign nevi better (p < .0001). The accuracy of clinical assessment in atypical nevi and melanoma was lower (23% and 42%, respectively). Seborrheic keratosis was the most common mistaken diagnosis. Complete removal of clinically benign nevi, atypical nevi, and melanoma was 84%, 90%, and 89%. Decision-making impaired clinical assessement of melanocytic lesions by 5% for dermatologists and 9% for nondermatologists. Conclusion: The accuracy of clinical assessment of melanocytic lesions is high for benign nevi, with dermatologists outperforming nondermatologists. Clinicians overestimated malignant potential. Complete removal was more frequent in suspicious lesions. Clinical decision-making impaired assessment by 5 to 9%.

Klarzellsarkom der Haut bei einem 12‐jährigen Jungen

primär kutane Klarzellsarkome sind selten. Ihre histopathologische Abgrenzung insbesondere von atypischen dermalen Spitz-Nävi und spindelzelligen/spitzoiden Melanomen kann Schwierigkeiten bereiten. Hilfreich hierbei kann der Nachweis bestimmter chromosomaler Veränderungen im Bereich des Ewing-Sarkom (EWS)-Gens sein. Ein 12-jähriger Junge wurde mit einem seit fünf Monaten bestehenden Knoten am linken Außenknöchel vorstellig. Dieser sei in den letzten Monaten etwas größenprogredient und schmerzhaft gewesen. Sonstige Beschwerden oder Erkrankungen bestanden nicht. Bei der klinischen Untersuchung zeigte sich ein derber und kaum verschieblicher, scharf begrenzter, ca. 1 cm durchmessender und über das Hautniveau deutlich erhabener, indolenter, erythematös-livider Knoten am linken Außenknöchel (Abbildung 1). Periphere Lymphknoten waren nicht palpabel. In der histologischen Untersuchung zeigt sich unter einem vorgewölbten, leicht akanthotischen Epithel eine überwiegend faszikulär, zum Teil in Nestern aufgebaute, dermal lokalisierte Zellproliferation (Abbildung 2a). Entlang der Junktionszone fi nden sich vereinzelt melanozytäre Nester. Auch in den tieferen dermalen Abschnitten dominiert ein faszikulärer Aufbau. Die Zellen weisen größere ovaläre Kerne und ein blass-eosinophiles Zytoplasma auf. Zudem sind auch in tieferen Anteilen vereinzelte Mitosen nachweisbar (Abbildung 2b). Immunhistochemisch ist die Läsion S100-Proteinund Melan-A-, nicht jedoch HMB45-positiv. Aufgrund der Histomorphologie wurde ergänzend eine Fluoreszenz-insitu-Hybridisierung (FISH) [1] zum Nachweis einer Translokation im Bereich des EWS-Gens durchgeführt. Diese konnte in einem Teil der Zellkerne (10/50) nachgewiesen werden. Anhand der vorliegenden Befunde stellten wir die Diagnose eines primär kutanen Klarzellsarkoms. Es erfolgten Clinical Letter

Cutaneous clear cell sarcoma in a 12‐year‐old boy

Primary cutaneous clear cell sarcomas are rare. Their histologic differentiation particularly from atypical dermal Spitz nevi and spindle cell/ spitzoid melanomas can prove to be difficult. Here the detection of certain chromosomal alterations on the Ewing sarcoma gene (EWS) can be helpful. A 12-year-old boy presented with a nodule on the left lateral malleolus that had been noticed five months ago. It had grown in recent months and had been painful. Other signs and symptoms or diseases did not exist. During clinical examination a solid, hardly-movable, elevated, painless, redviolet nodule about 1 cm in diameter with sharp borders was seen on the left lateral malleolus (Figure 1). Peripheral lymph nodes were not palpable. Histology revealed a domed lesion with slightly acanthotic epithelium with a dermal cell proliferation arranged primarily in a fascicular structure, in part in nests (Figure 2a). Along the junction zone some melanocytic nests were seen. In the deeper dermal regions a fascicular pattern dominated. The cells had large, oval nuclei and a pale eosinophilic cytoplasm. Further, in the deeper portions sporadic mitoses were detected (Figure 2b). Immunohistochemically the lesion was S100proteinand melan-A-positive, but HMB45-negative. Because of the histological findings, fluorescence in situ hybridization (FISH) [1] was performed searching for a translocation Correspondence in the EWS gene. The translocation was found in some of the cell nuclei (10/50). Based upon the findings we diagnosed a primary cutaneous clear cell sarcoma. Subsequently a re-excision with 2 cm safety margins as well as the removal of two sentinel lymph nodes was performed. Marginal sinus infiltration was suspected in both of the nodes (2/2) so they also were subjected to FISH analysis but no translocations in the EWS gene were identified. The sinus changes were thus interpreted as lymph node nevi. An interdisciplinary skin cancer board recommended dissection of the left inguinal lymph nodes, which was performed in the Clinic for Pediatric Surgery; all seven nodes were free of tumor (0/7). Staging (soft tissue sonography of the left lower leg, the lymph nodes and the abdomen, CT of