Sarcopenia and cardiovascular risk indices: Its impact on cardiovascular events and mortality in dialysis patients.

BACKGROUND: Sarcopenia is a common complication in end-stage renal disease. Low muscle strength and muscle mass are risk factors for cardiovascular disease and mortality in patients undergoing dialysis. We studied the relation between sarcopenia and pre-atherosclerotic markers and its effect on cardiovascular events and death in dialysis patients. METHODS: We measured muscle strength, muscle mass, carotid intima-media thickness, and pulse wave velocity in 106 patients. Sarcopenia was diagnosed according to the EWGSOP-2 suggestions. Patients with low muscle strength and low muscle mass were considered sarcopenic. The follow-up period for cardiovascular events and mortality was 24 months. RESULTS: The mean age and dialysis duration were 57.4 ± 16.6 and 6.5 ± 4.9 years, respectively. Of all patients, 53 (50%) were male and 70 (66%) were on hemodialysis treatment. Sarcopenia and low muscle strength were seen in 47.1% and 88.7%, respectively. Hemodialysis patients were more likely to be sarcopenic than peritoneal dialysis patients (p = 0.001). Ferritin and Kt/V levels were higher, and body mass index was lower significantly in sarcopenic patients (p < 0.001). There was no significant difference in carotid intima-media thickness and pulse wave velocity measurements between the groups (p = 0.62 and p = 0.68, respectively). There was no statistically significant difference in cardiovascular events and mortality in cases with and without sarcopenia (p = 0.43 and p = 0.17, respectively). CONCLUSION: There was no association between sarcopenia and pre-atherosclerotic markers, cardiovascular events, and all-cause mortality in dialysis patients. Techniques to detect low muscle strength and muscle mass need standardization, and new specific cut-off levels must be defined for dialysis patients.

Zunahme des atypischen Fibroxanthoms und pleomorphen dermalen Sarkoms: eine retrospektive Analyse vier deutscher Hauttumorzentren.

HINTERGRUND UND ZIELE: In den letzten Jahren konnten umfassende Erkenntnisse über die Pathogenese, Diagnostik und Behandlung von kutanen Sarkomen, insbesondere des atypischen Fibroxanthoms (AFX) und pleomorphen dermalen Sarkoms (PDS) gesammelt werden. Beide Entitäten zeigten innerhalb der letzten Dekade steigende Inzidenzraten. Die vorliegende Studie diente der Untersuchung, welchen Einfluss die neuen Erkenntnisse auf die Fallzahlen von AFX/PDS im Vergleich zu anderen Sarkom-Entitäten haben. PATIENTEN UND METHODIK: Diese retrospektive Studie wurde an vier deutschen Hauttumorzentren durchgeführt und alle von zertifizierten Dermatopathologen bestätigten histopathologischen Befunde von kutanen Sarkomen (AFX, PDS, Dermatofibrosarcoma protuberans, kutanes Leiomyosarkom, Angiosarkom und Kaposi-Sarkom) in einem Zeitraum von sieben Jahren (2013-2019) evaluiert. Zusätzlich wurde der Einsatz von immunhistochemischen Markern als diagnostische Hilfe (Panzytokeratin, S100, Desmin, CD34, CD10, Prokollagen-1, CD99, CD14 und CD68) erfasst. ERGEBNISSE: Insgesamt konnten 255 kutane Sarkome in die vorliegende Studie eingeschlossen werden. Die Zahl der kutanen Sarkome nahm kontinuierlich von 2013 bis 2019 zu (von 16 auf 52 Fälle im Jahr). Die Diagnose eines AFX/PDS konnte in 2019 4,6-mal häufiger als in 2013 gestellt werden. Das AFX stellte mit 49,3 % aller kutanen Sarkome den häufigsten Sarkom-Subtypen dar. Zusätzlich war der Anstieg von AFX/PDS mit dem Einsatz von Immunhistochemie assoziiert. Der Einsatz von spezifischen Immunhistochemischen Markern stieg von 57,1 % im Jahr 2013 auf 100 % in 2019. SCHLUSSFOLGERUNGEN: Diese retrospektive Studie von vier deutschen Hauttumorzentren demonstriert eine substanzielle Zunahme von AFX/PDS, wahrscheinlich infolge kürzlich etablierter beziehungsweise verbesserter diagnostischer und terminologischer Standards. Dieser Anstieg ist vermutlich mit dem vermehrten Einsatz von bestimmten immunhistochemischen Markern assoziiert. AFX/PDS treten wahrscheinlich häufiger auf als bisher vermutet und repräsentieren möglicherweise den häufigsten kutanen Sarkom-Subtyp.

Increase of atypical fibroxanthoma and pleomorphic dermal sarcoma: a retrospective analysis of four German skin cancer centers.

BACKGROUND AND OBJECTIVES: In recent years, considerable insight has been gained into the pathogenesis, diagnosis and treatment of cutaneous sarcomas, including atypical fibroxanthoma (AFX) and pleomorphic dermal sarcoma (PDS). Both entities have shown increasing incidence rates in the last decade. This study was initiated to evaluate how these new insights impact the number of diagnoses of AFX/PDS compared to other cutaneous sarcoma entities. PATIENTS AND METHODS: In a retrospective study of four German skin cancer centers, all histopathological reports of cutaneous sarcomas (AFX, PDS, dermatofibrosarcoma protuberans, cutaneous leiomyosarcoma, angiosarcoma, and Kaposi sarcoma) confirmed by board-certified dermatopathologists were analyzed during a time-period of seven years (2013-2019). Additionally, utilization of immunohistochemical markers (including pan-cytokeratin, S100, desmin, CD34, CD10, procollagen-1, CD99, CD14, and CD68) as an adjunct to diagnose AFX/PDS was recorded. RESULTS: Overall, 255 cutaneous sarcomas were included in the present study. The diagnosis of a cutaneous sarcoma has consequently risen from 2013 to 2019 (from 16 to 52 annual cases). The results of AFX/PDS revealed 4.6 times more diagnoses in 2019 than in 2013. Atypical fibroxanthoma represented the most common subtype, displaying 49.3 % of all diagnosed cutaneous sarcomas. Additionally, the increase of AFX/PDS was linked to the use of immunohistochemistry, with specific immunohistochemical markers used in 57.1 % of cases in 2013 compared to 100 % in 2019. CONCLUSIONS: This retrospective study of four German skin cancer centers demonstrates a substantial rise of AFX/PDS, possibly due to recently established diagnostic and terminology standards. This rise is probably linked to increased utilization of specific immunohistochemical markers. Atypical fibroxanthoma/PDS may be more common than previously thought and seems to represent the most frequent cutaneous sarcoma subtype.

Instep split skin grafts on muscle flaps to reconstruct pressure exposed soft tissue parts at the lower extremity.

BACKGROUND: Reconstructed mechanically stressed zones of the lower extremity frequently suffer from problems such as hyperkeratotic edges or chronic ulcerations in the transition zone between conventional thigh skin grafts and normal skin. Defect coverage with skin grafts harvested from the instep region and placed on muscle flaps is not yet an established alternative. METHODS: This is a retrospective study of a series of 12 clinical applications of soft tissue reconstruction at mechanically exposed zones of the lower extremity. Locally transposed or transplanted muscle flaps were covered with meshed instep skin instead of meshed thigh skin for the purpose to gain a superior stable skin surface and transition zones adjacent to normal skin. RESULTS: There is no ulceration found at follow-up from 6 to 72 months. Only one case presented with delayed graft take. Different thicknesses of the corneal layers of the healed instep versus thigh skin grafts were verified histologically. Instep skin grafts showed substantial durability as well as advantageous aesthetic appearance with respect to texture and coloring. All donor sites healed without notable scars or sensitivity disorders. CONCLUSIONS: The instep split skin graft is particularly well suited for defect coverage of muscle flaps transposed or transplanted to mechanically stressed zones of the foot or lower leg. The paramount advantage of transplanted instep skin as compared to thigh skin is given by the feasibility to create a durable graft with a thick horny layer and a stable transition zone at its periphery that is bordering normal skin.

Multiple (familial) trichoepitheliomas: a clinicopathological and molecular biological study, including CYLD and PTCH gene analysis, of a series of 16 patients.

Multiple familial trichoepitheliomas (MFT) constitute an autosomally inherited syndrome possibly related to Brooke-Spiegler syndrome (BSS). Although some early studies suggested a role for the PTCH gene on chromosome 9q22.3 in the etiopathogenesis of MFT, recent studies of occasional patients with the MFT clinical phenotype identified mutations in the CYLD gene on chromosome 16q12-q13, a gene responsible for BSS. A systematic investigation of PTCH and CYLD mutations in patients with MFT has never been performed. Our main objective was to collect a reasonably large series of patients with MFT to (1) study the clinicopathological spectrum of the disease, (2) determine whether the PTCH gene is implicated in the pathogenesis of MFT, and if so (3) determine the relative frequency of CYLD and PTCH mutations, (4) establish if there may be any possible genotype-phenotype correlations, and (5) study the spectrum of somatic mutations. Clinical analysis including family histories, histopathological investigations, and molecular genetic studies were performed. There were 9 female and 7 male patients ranging in age from 11 to 63 years. They presented with multiple, small, discrete and sometimes confluent, skin-colored to pink, asymptomatic nodules preferentially located on the face, being especially prominent and confluent in the nasolabial folds and inner aspects of the eyebrows. A total of 66 conventional trichoepitheliomas (TEs) were studied microscopically. Aside from typical features of TE, some also exhibited variant morphological patterns including areas reminiscent of other benign adnexal neoplasms and melanocytic hyperplasia. In none of the 9 patients tested was a germline mutation of the PTCH gene identified. Germline CYLD mutations were detected in 6 of 13 patients tested (identical in 2 unrelated patients) including 2 novel mutations, whereas the remaining 7 individuals showed wild-type alleles. Two patients with germline wild-type CYLD showed, however, a somatic mutation in the gene (1 duplication, 1 substitution mutation). Neither CYLD nor PTCH germline mutations were found in the 5 patients in whom both genes were analyzed. MFT seems to be a phenotypic variant of BSS. The PTCH gene is rarely, if ever, involved in the pathogenesis of MFT. Absence of a germline mutation of the CYLD gene in cases harboring a somatic mutation may be explained by large deletions in the gene or by mutation in intronic sequences or in the promoter region. Considering our 5 patients with no mutation in either gene, the final possibility is that another, as yet undescribed gene (neither CYLD nor PTCH) is implicated in the pathogenesis of some patients with MFT.

Paraneoplastic Filiform Hyperkeratosis and Immunoglobulin-Associated Vasculitis in Myeloma Progression: A Case Report.

Multiple myeloma is a lymphoproliferative disease, which rarely presents with skin involvement or associated symptoms. Better awareness of these dermatological presentations is required for early diagnosis and to guide the patient towards appropriate therapy. We report on a patient with diffuse filiform hyperkeratosis and immunoglobulin-associated vasculitis in a severe progression of a known myeloma.

Highlighting the Prognostic Importance of Measurable Residual Disease Among Acute Myeloid Leukemia Risk Factors

Objective: The optimal timing of measurable residual disease (MRD) evaluation in acute myeloid leukemia (AML) patients has not been well defined yet. We aimed to investigate the impact of MRD in pre- and post-allogeneic hematopoietic stem cell transplantation (AHSCT) periods on prognostic parameters. Materials and Methods: Seventy-seven AML patients who underwent AHSCT in complete morphological remission were included. MRD analyses were performed by 10-color MFC and 10-4 was defined as positive. Relapse risk and survival outcomes were assessed based on pre- and post-AHSCT MRD positivity. Results: The median age of the patients was 46 (range: 18-71) years, and 41 (53.2%) were male while 36 (46.8%) were female. The median follow-up after AHSCT was 12.2 months (range: 0.2-73.0). The 2-year overall survival (OS) in the entire cohort was 37.0%, with a significant difference between patients who were MRD-negative and MRD-positive before AHSCT, estimated as 63.0% versus 16.0%, respectively (p=0.005). MRD positivity at +28 days after AHSCT was also associated with significantly inferior 2-year OS when compared to MRD negativity (p=0.03). The risk of relapse at 1 year was 2.4 times higher (95% confidence interval: 1.1-5.6; p=0.04) in the pre-AHSCT MRD-positive group when compared to the MRD-negative group regardless of other transplant-related factors, including pre-AHSCT disease status (i.e., complete remission 1 and 2). Event-free survival (EFS) was significantly shorter in patients who were pre-AHSCT MRD-positive (p=0.016). Post-AHSCT MRD positivity was also related to an increased relapse risk. OS and EFS were significantly inferior among MRD-positive patients at +28 days after AHSCT (p=0.03 and p=0.019). Conclusion: Our results indicate the importance of MRD before and after AHSCT independently of other factors.

High prevalence of 'Borrelia-like' organisms in skin biopsies of sarcoidosis patients from Western Austria.

BACKGROUND: Sarcoidosis is a multisystem granulomatous disorder of unknown aetiology with frequent skin involvement. OBJECTIVE: To investigate the frequency of 'Borrelia-like' organisms in cutaneous sarcoidosis (CS) by focus-floating microscopy (FFM). METHODS: Retrospective analysis of 38 CS specimens by immunohistochemistry with polyclonal anti-Borrelia antibody and assessment by FFM. RESULTS: Specimens of 34.2% CS were positive for 'Borrelia-like' organisms by FFM. Usually single spirochetes, rarely pairs or small clusters of bacteria were observed between collagen bundles or at the periphery of granulomas. Polymerase chain reaction (PCR) was performed in addition in 11 cases and was negative in all biopsies. Samples of erythema migrans served as positive controls: 92.3% of 39 samples were positive by FFM, but only 46.6% gave positive results by PCR. Of 61 negative controls only one specimen was falsely positive by immunohistochemistry. CONCLUSION: Detection of 'Borrelia-like' organisms by FFM in tissue sections of CS underlines the possibility that such microorganism maybe involved in the pathogenesis of some cases of CS.

Granuloma annulare--a manifestation of infection with Borrelia?

BACKGROUND: Among the theories of origin of granuloma annulare (GA) are those of infection. Reports gave raise to the assumption that there is evidence for Borrelia as the causing agent. METHODS: To assess the evidence for infection with Borrelia in GA, tissue sections were stained with a polyclonal Borrelia antibody. With focus-floating microscopy (FFM), slides were scanned at a 200- to 400-fold magnification. Part of the material was also investigated with a Borrelia-specific polymerase chain reaction (PCR). RESULTS: A total of 157 biopsies of GA have been investigated. Using FFM, Borrelia were detected in 127 cases of GA (80.9%). Borrelia were more prominent in localized (85.2%) than in diffuse GA (62.1%). In 27 cases of GA analysed by PCR, Borrelia-specific DNA could be detected in only one case (3.7%), but was positive in 21 cases by FFM (77.8%). About 93.3% of 15 control cases of borreliosis were positive with FFM and 46.7% with PCR, while all controls other than borreliosis remained negative for spirochetes. CONCLUSION: FFM is a reliable method to show Borrelia in tissue sections of GA, which is more sensitive than PCR. This underlines the possibility that Borrelia are involved specifically in the aetiology and pathogenesis of GA.

Mucinous carcinoma of the skin, primary, and secondary: a clinicopathologic study of 63 cases with emphasis on the morphologic spectrum of primary cutaneous forms: homologies with mucinous lesions in the breast.

We present the largest series of mucinous carcinoma involving the skin, describing the histopathologic, immunohistochemical, electron microscopic, and cytogenetic findings. Our aim was fully to characterize the clinicopathologic spectrum and compare it with that seen in the breast. In addition, we wished to reevaluate the differential diagnostic criteria for distinguishing primary mucinous carcinomas from histologically similar neoplasms involving the skin secondarily, and study some aspects of their pathogenesis. We demonstrate that primary cutaneous mucinous carcinomas span a morphologic spectrum compatible to their mammary counterparts. Both pure and mixed types can be delineated morphologically, and some lesions have mucocele-like configurations. Most lesions seem to originate from in situ lesions that may represent, using mammary pathology terminology, ductal hyperplasia, atypical ductal hyperplasia, or ductal carcinoma in situ or a combination of the three. Inverse cell polarity appears to facilitate the progression of the changes similar to lesions in the breast. The presence of an in situ component defines the neoplasm as primary cutaneous, but its absence does not exclude the diagnosis; although for such neoplasms, full clinical assessment is essential. Mammary mucinous carcinoma involving the skin: all patients presented with lesions on chest wall, breast, axilla, and these locations can serve as clue to the breast origin. Microscopically, cutaneous lesions were of both pure and mixed type, and this correlated with the primary in the breast. Dirty necrosis was a constant histologic finding in intestine mucinous carcinomas involving the skin, and this feature may serve as a clue to an intestinal origin.

Histologic features of cutaneous lupus erythematosus.

Histologic examination of lesions plays a key role in the diagnostics of cutaneous lupus erythematosus (LE). LE has a broad spectrum of histopathological signs, which are related to the stages of the lesions. In addition to the main subtypes of LE, we report on special manifestations like Rowell's-syndrome and Chilblain LE, and give an account of Kikuchi-Fujimoto disease (histiocytic necrotizing lymphadenitis), which may be associated with systemic LE. Furthermore the most considerable histopathologic differential diagnoses are discussed.

[Elastolytic granulomas of the legs in familial visceral lymphangiodysplasia with chronic lymphedema]. / Elastolytische Granulome der Beine bei familiärer viszeraler Lymphangiodysplasie mit chronischem Lymphödem.

Annular elastolytic giant cell granuloma is a rare skin condition of unknown origin characterized by giant cell granulomas with elastophagocytosis and loss of elastic tissue. Sun-exposed areas are most commonly affected. We report on an unusual case of elastolytic granulomas developing in chronic lymphedema of the legs in a female patient with visceral lymphangiodysplasia.