Lacking CD56 expression in a relapsing cutaneous blastic plasmacytoid dendritic cell neoplasm after allogeneic bone marrow transplantation: FISH analysis revealed loss of 11q.

BACKGROUND: Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare entity characterized by a CD4+/CD56+/CD123+ immunophenotype and a fatal clinical course. The average survival of 12-14 months may be prolonged by allogeneic bone marrow transplantation (BMT). OBJECTIVES: We report about a male patient who suffered from BPDCN with a typical histology and co-expression of CD4/CD123 and a CD56 expression by 80% of the tumour cells. The cutaneous tumour relapse after chemotherapy and allogeneic BMT was completely negative for CD56. METHODS: We performed interphase fluorescence in situ hybridization (FISH) analysis of tumour tissue, asserved before and after BMT, using specific probes for chromosome 11, which encompass the CD56 gene region. RESULTS: The tumour cells revealed a partial loss of 11q as well as a monosomy of chromosome 11. CONCLUSION: This case demonstrates for the first time that loss of CD56 expression can also occur as a secondary event after chemotherapy and BMT. In our case, DNA loss of 11q23 could be responsible for the negativity of 20% of tumour cells as observed before chemotherapy. However, the complete loss of CD56 expression in the relapsed tumour cannot be explained by the loss of 11q23 alone. Additional factors such as chemotherapy-induced mutations might also have contributed.

[Treatment of disseminated granuloma annulare with anthralin]. / Therapie des Granuloma anulare disseminatum mit Anthralin.

Granuloma annulare is a benign, often asymptomatic and self-limiting granulomatous skin disease. In cases of disseminated granuloma annulare, spontaneous regression is considerably less frequent than in localized forms so that therapy is often desired. Systemic treatments should always be assessed critically and reserved for patients who are severely affected and in whom treatment approaches with few side effects such as local application of anthralin do not suffice to achieve a satisfactory effect.

[Uncommon cutaneous ulcerative and systemic sarcoidosis. Successful treatment with hydroxychloroquine and compression therapy]. / Seltene ulzerierende kutane und systemische Sarkoidose. Erfolgreiche Therapie mit Hydroxychloroquin und medizinischer Kompressionstherapie.

Sarcoidosis is a granulomatous multisystemic disease of unclear etiology, which can affect any organ. The cutaneous manifestations are variable, but ulcerative cutaneous sarcoidosis is very rare. One must rule out other granulomatous skin diseases, especially necrobiosis lipoidica. There is no standarized therapy; usually an interdisciplinary approach over years taking multiple side effects into consideration is needed. A 58-year-old woman with a long history of cutaneous, nodal and pulmonary sarcoidosis suddenly developed ulcerations within the disseminated skin lesions on her legs. The combination of systemic hydroxychloroquine and modern wound management lead to complete healing of the ulcers and a significant improvement in the remaining skin lesions.

Papular exanthem discloses acute myeloid leukaemia: interphase fluorescence in situ hybridization revealed deletion of p53 and gain at 8q22/8q24/Tel8q without trisomy 8.

We describe a 79-year-old patient who presented with fatigue, weight loss, pancytopenia and a papular exanthem. Previous attempts to taking bone-marrow biopsies had resulted in a 'dry tap', with no material collected, suggesting idiopathic myelofibrosis. Histological examination of skin biopsies showed dermal infiltration of monocytoid cells, resulting in a diagnosis of acute myeloid leukaemia (French-American-British M5 morphology) with leukaemia cutis (LC). Numerous abnormalities of chromosome 8 (trisomy or tetrasomy) have been identified in association with LC. We performed fluorescent in situ analysis on cutaneous tissue using directly labelled probes for various gene loci often involved in patients with AML; these tests showed deletion of p53 and excluded trisomy 8. However, application of probes for AML/ETO, MYC and telomere 8q revealed a gain at 8q22/8q24/8q telomere in a significant number of infiltrating cells. We hypothesize that a partial gain at 8q rather than trisomy of the whole chromosome 8 exhibits an association with LC in AML.

[A rare case of a sclerodermoid chronic graft versus host disease. Successful treatment with extracorporeal photopheresis (ECP)]. / Ungewöhnliche chronische sklerodermiforme Graft-versus-Host-Erkrankung : Erfolgreiche Therapie mittels extrakorporaler Photopherese (ECP).

A 31-year-old woman presented with progressive deep linear induration on her lower abdomen, forearms and thighs. These symptoms developed three years after allogenic stem cell transplantation. Furthermore, the patient showed multiple hypopigmented lichenoid papules on the extensor surfaces of the forearms consistent with lichen sclerosus. Histological analysis of a biopsy specimen from her left thigh showed dermal sclerosis extending into the fascia, thus establishing the diagnosis of a rare combination of superficial and deep sclerodermoid chronic graft-versus-host disease. After 7 cycles of extracorporeal photopheresis, a marked resolution of the indurations and a reduction of the modified Rodnan skin score from 12 to 7 were noted.

[Unusual combination of clinical forms in a young man. Atypical pityriasis rosea]. / Ungewöhnliche Kombination von klinischen Morphen bei einem jungen Mann. Atypische Pityriasis rosea.

Uncommon forms of pityriasis rosea (PR) are found in a not inconsiderable proportion of patients (totaling approximately 20%) and predominantly affect children and young adults. They are characterized by atypical morphology and distribution of the primary medallion or also of the subsequent exanthematous individual lesions. The etiology of PR is not yet known. It is possible that the underlying cause of PR is viral in origin.

Sentinel lymphonodectomy does not increase the risk of loco-regional cutaneous metastases of malignant melanomas.

With regard to malignant melanoma, the impact of lymph node surgery on the development of loco-regional cutaneous metastases (LCM) has not yet been adequately addressed. However, this aspect is of interest, since sentinel lymphonodectomy (SLNE) has been suspected of causing LCM by inducing entrapment of melanoma cells. We analysed 244 patients with SLNE and compared the data with 199 patients treated with delayed lymph node dissection (DLND) for clinically palpable metastases. Analysis of both groups commenced at the time of excision of the primary tumour, using the Kaplan-Meier method. LCM that appeared as a first recurrence, as well as the overall probability of developing LCM, were recorded. For sentinel-negative patients with a primary melanoma >1mm thick, the 5-year probability of developing LCM as a first recurrence was 6.9 +/- 0.02% (+/-standard error of the mean (SEM)). The probability was 17.6 +/- 0.03% in the DLND group. Comparing the two node-positive subgroups, the probability of developing LCM as a first recurrence was significantly higher in patients with positive SLNE (27.3 +/- 0.05%, P = 0.03). However, the 5-year overall probability of developing LCM did not differ significantly in the node-positive groups (33.3% in the DLND group vs. 33.7% in patients with positive sentinel lymph nodes (SLNs)). Since early excision of lymphatic metastases by SLNE avoids nodal recurrences, thereby prolonging the recurrence-free interval, the chance of LCM to manifest as a first recurrence should inevitably increase. However, the overall in-transit probability is not increased after SLNE.

Results of a surveillance programme for patients at high risk of malignant melanoma using digital and conventional dermoscopy.

Patients with a high number of atypical naevi and a personal and/or family history of melanoma are at high risk of malignant melanoma. The objective of this study was to design a special documentation and surveillance programme using epiluminescence microscopy (ELM) and digital epiluminescence microscopy (DELM) to improve the surveillance of these patients. High-risk patients (n=212) were categorized by the number and phenotype of their naevi and their personal and family history of melanoma. Then patients were screened by the unaided eye, conventional photography, ELM and, in selected cases of atypia, DELM. Median follow-up was 18 months, and 2939 pigmented lesions were followed by DELM. Examination on the first visit identified 17 cutaneous melanomas. During the following observation period, another 17 melanomas were identified. Fifteen of these follow-up melanomas were exclusively identified based upon DELM. In these cases, subtle lesional changes occurred over time, and ELM diagnostic algorithms for differentiating benign melanocytic lesions from melanoma did not score a suspicion of melanoma. All melanomas, either pre-existing or developing during follow-up, were identified in an early, curable phase of tumour growth. We conclude that DELM follow-up for patients at high risk allows the early detection of melanomas that have not yet acquired melanoma-typical ELM features.

CD4+ CD56+ blastic tumor of the skin: cytogenetic observations and further evidence of an origin from plasmocytoid dendritic cells.

We here report on a case of a blastic tumor, recently described to belong to a new entity sharing phenotypic similarities with blood derived plasmocytoid dendritic cells and formerly regarded as belonging to the group of natural killer cell lymphomas. Besides immunophenotypic characteristics such as the absence of T- cell markers and almost complete absence of markers of the myeloid lineage, these tumors express CD4, CD56 and CD123, the receptor for interleukin-3. Moreover, using the comparative genomic hybridisation technique, CGH, we demonstrate a gain of chromosome 7q, 22 and a loss of chromosome 3p and 13q. Since this type of hematologic disorder often shows its primary manifestation in the skin and often runs a rapidly fatal course, it is important to distinguish this from other types of primary cutaneous lymphomas.

Proliferating cell nuclear antigen (PCNA) expression of megakaryocytopoiesis in normal human bone marrow and reactive lesions with special emphasis on HIV-myelopathy.

A morphometric analysis was performed on bone marrow trephine biopsies using sequential double-immunostaining, to evaluate endoreduplicative activity of megakaryocytopoiesis. A total of 104 marrow specimens were studied with employment of monoclonal antibodies PC10 (anti-proliferating cell nuclear antigen-PCNA) and Y2/51-CD61 (anti-platelet glycoprotein IIIa). In addition to the control group patients included non-specific inflammatory changes, HIV-myelopathy with normal or decreased platelet counts, idiopathic thrombocytopenic purpura (ITP), and finally reactive thrombocytosis (TH). To exclude an undue overexpression of PCNA, in a comparative pilot study we also applied MIB1 (Ki-67 antigen) on normal bone marrow specimens. In accordance with the various modalities of cell-cycle marker expression, no significantly different findings were disclosed. PCNA-labelling index was relatively low, ranging from 0.8 to 1.7% of the total megakaryocytopoiesis (promegakaryoblasts to mature platelet-shedding megakaryocytes). A significant relationship between megakaryocyte size and PCNA-expression was determinable. This implies that some of the cases with a prevalence of small megakaryocytes, like ITP, have the tendency to show a higher proportion of positively-stained cells. Moreover, this feature confirms a hypothesis postulating a decrease in the time for DNA-synthesis (S-phase) and a relative prolongation of the G1/G2-phases of the cell-cycle at higher ploidy levels (large-sized megakaryocytes). On the other hand, it may be speculated that some of the hyperpolyploid giant megakaryocytes may have reached their endstage of endoreduplication and enter into G0-phase. In comparison with the control group and the other entities under study, a significant reduction of PCNA-reactivity was recognizable in HIV-myelopathy accompanied by thrombocytopenia.(ABSTRACT TRUNCATED AT 250 WORDS)

Pro-megakaryoblasts in bone marrow tissue from patients with primary (idiopathic) osteo-myelofibrosis (agnogenic myeloid metaplasia). An immunomorphometric study on trephine biopsies.

An immunomorphometric study was performed on bone marrow biopsies from 40 patients with primary osteomyelofibrosis--OMF, (agnogenic myeloid metaplasia) by employment of a monoclonal antibody against glycoprotein IIIa (Y2/51) to determine the number of pro-megakaryoblasts. Specimens from 15 individuals without any hematological disorder served as controls. With reference to the pertinent literature on megakaryocyte precursors and following a pilot study on corresponding smears, in tissue sections pro-megakaryoblasts were characterized by a size of 42.1 +/- 2.6 microns 2 (diameter 7.5 +/- 0.3 microns). In comparison with controls, in OMF no relevant increase in the number of pro-megakaryoblasts per square and cubic millimeter bone marrow was evaluable. The relative frequency of these precursors was significantly reduced due to an increase in the total amount of conspicuously large and abnormal megakaryocytes. Statistical analysis failed to reveal any correlations between counts for pro-megakaryoblasts or the total number of Y2/51--positive megakaryocytic elements with the density of argyrophilic fibers (determined by morphometry) or the platelet values. Our findings imply that in OMF the marked increase in circulating progenitor cells of the megakaryocyte lineage may be generated by extramedullary, probably splenic hematopoiesis. Moreover, the evolution of medullary fibrosis is thought to be associated with the striking predominance of large atypical, possibly overaged and hyperpolyploid megakaryocytes and not with an increase in precursor cells.

Acroangiodermatitis Mali resulting from arteriovenous malformation: report of a case of Stewart-Bluefarb syndrome.

We describe the rare Stewart-Bluefarb syndrome in a 15-year-old boy. This syndrome presents as a congenital arteriovenous malformation of the lower leg with multiple arteriovenous shunts accompanied by the benign acroangiodermatitis of Mali (pseudo-Kaposi's sarcoma). The clinical features of this disorder and the treatment options are reviewed.

[Painful cutaneous leiomyosarcoma]. / Schmerzhaftes kutanes Leiomyosarkom.

Leiomyosarcomas are derived from smooth muscles and only rarely involve the skin. A 73-year-old male presented with progressive tumor painful on the chest which had been present for 3 years and was tender to palpation, a finding more often associated with benign leiomyomas. immunohistochemical staining demonstrated multiple nerve fibers entrapped by atypical myofibrils, perhaps explaining the tenderness. Since 1996, we have excised five painless cutaneous leiomyosarcomas, in which entrapped nerves could not be demonstrated.

Myelodysplastic syndromes: immunohistochemical and morphometric evaluation of proliferative activity in erythropoiesis and endoreduplicative capacity of megakaryocytes.

An immunohistochemical and morphometric analysis was performed on bone marrow trephine biopsies in 40 patients with primary myelodysplastic syndromes (MDS) to evaluate the proliferative activity in erythropoiesis and the endoreduplicative capacity of megakaryocytes. Control groups included normal bone marrow and marrow from cases presenting with pernicious anaemia. Double-immunostaining was applied with a monoclonal antibody (PC10) directed against proliferating cell nuclear antigen (PCNA), followed by antibodies against glycophorin C (Ret40f) or platelet glycoprotein IIIa (Y2/51-CD61) for the identification of the erythroid and megakaryocytic cell lineage. Comparison with normal bone marrow showed a reduction of erythropoiesis accompanied by an increase in atypical (micro-) megakaryocytes. Erythroid precursors displayed significant enhancement of PCNA-immunostaining. Megakaryocytes showed no increase in the relative frequency of PC10-positive cells (PCNA-labelling index). In pernicious anaemia, predominance of macrocytic-megaloblastoid erythropoiesis was associated with a striking increase in PCNA-labelling. Cell kinetic studies in this disorder revealed an abnormal arrest, particularly in S-phase which generates an over-expression of PCNA. Similar conditions were believed to be present in MDS with secondary folate deficiency. This mechanism explains the relatively high rate of positively-reacting pro- and erythroblasts which is not invariably accompanied by an increase in cell proliferation. Determination of megakaryocyte size and PCNA-staining capacity resulted in a significant increase in PC10-positive cells among micromegakaryocytes. Our findings on this cell lineage are in keeping with the assumption of a block in endoreduplicative activity at higher ploidy levels, associated with an apparently not-deregulated endomitosis in small-sized megakaryocytes of lower ploidy stages.

[Cutaneous sinus histiocytosis (Rosai-Dorfman disease)]. / Kutane Sinushistiozytose (Rosai-Dorfman-Erkrankung).

Sinus histiocytosis is as a rule a benign disease of lymph nodes, infiltrated by large histiocytes. These cells show typical cytophagocytosis, particularly lymphophagocytosis. Other organs may be also involved by this disease, often including the skin. Exclusive cutaneous sinus histiocytosis without infiltration of lymph nodes seems to be very rare. To exclude other non-X histiocytoses or histiocytosis-X, it is advisable to use immunohistochemistry. We report on a patient with sinus histiocytosis and discuss the problems of differential diagnosis.

Splenic megakaryocytopoiesis in primary (idiopathic) osteomyelofibrosis. An immunohistological and morphometric study with comparison of corresponding bone marrow features.

An immunohistochemical and morphometric study has been performed on splenic tissue of 10 patients with primary (idiopathic) osteomyelofibrosis (OMF) to determine characteristic features of megakaryocytopoiesis in myeloid metaplasia. Using the periodic acid-Schiff reaction (PAS) and particularly the monoclonal antibody CD61 (Y2/51), all elements of this cell lineage including precursors could be identified. In comparison with bone marrow specimens from our file material (40 patients with OMF, 15 control cases) which were processed in a similar way, megakaryocytes in the spleen revealed significant differences. These differences included smaller cell sizes, a disturbed nuclear-cytoplasmic ratio, and a conspicuous increase in the relative frequency of promegakaryoblasts. In conclusion, extramedullary megakaryocytopoiesis in OMF did not only show more pronounced abnormalities of differentiation, but also a higher degree of immaturity. Our finding of a significant accumulation of megakaryocytic precursors in the spleen as opposed to the bone marrow, corroborates the so-called filtration theory which has been introduced to explain the evolution of splenic myeloid metaplasia in OMF.