The Predictive Value of Graft Viability and Bioenergetics Testing Towards the Outcome in Liver Transplantation.

Donor organ biomarkers with sufficient predictive value in liver transplantation (LT) are lacking. We herein evaluate liver viability and mitochondrial bioenergetics for their predictive capacity towards the outcome in LT. We enrolled 43 consecutive patients undergoing LT. Liver biopsy samples taken upon arrival after static cold storage were assessed by histology, real-time confocal imaging analysis (RTCA), and high-resolution respirometry (HRR) for mitochondrial respiration of tissue homogenates. Early allograft dysfunction (EAD) served as primary endpoint. HRR data were analysed with a focus on the efficacy of ATP production or P-L control efficiency, calculated as 1-L/P from the capacity of oxidative phosphorylation P and non-phosphorylating respiration L. Twenty-two recipients experienced EAD. Pre-transplant histology was not predictive of EAD. The mean RTCA score was significantly lower in the EAD cohort (-0.75 ± 2.27) compared to the IF cohort (0.70 ± 2.08; p = 0.01), indicating decreased cell viability. P-L control efficiency was predictive of EAD (0.76 ± 0.06 in IF vs. 0.70 ± 0.08 in EAD-livers; p = 0.02) and correlated with the RTCA score. Both RTCA and P-L control efficiency in biopsy samples taken during cold storage have predictive capacity towards the outcome in LT. Therefore, RTCA and HRR should be considered for risk stratification, viability assessment, and bioenergetic testing in liver transplantation.

Tumor of follicular infundibulum - reappraisal in a series of 28 patients with critical review of the literature.

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.

Vasculitides and occluding vasculopathies, challenges in recognizing histopathological patterns, and their solutions.

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.

Hide-and-seek: Neurotropes Plattenepithelkarzinom der periorbitalen Region - eine Fallserie und Übersichtsarbeit aktueller Literatur.

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.

Hide-and-seek: Neurotropic squamous cell carcinoma of the periorbital region - a series of five cases and review of the literature.

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.

Seborrheic Keratosis With Sebaceous Differentiation, a Series of 8 Cases and Critical Review of the Literature.

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.

Long-term outcome after hand and forearm transplantation - a retrospective study.

Between 2000 and 2014, five patients received bilateral hand (n = 3), bilateral forearm (n = 1), and unilateral hand (n = 1) transplants at the Innsbruck Medical University Hospital. We provide a comprehensive report of the long-term results at 20 years. During the 6-20 years follow-up, 43 rejection episodes were recorded in total. Of these, 27.9% were antibody-related with serum donor-specific alloantibodies (DSA) and skin-infiltrating B-cells. The cell phenotype in rejecting skin biopsies changed and C4d-staining increased with time post-transplantation. In the long-term, a change in hand appearance was observed. The functional outcome was highly depending on the level of amputation. The number and severity of rejections did not correlate with hand function, but negatively impacted on the patients´ well-being and quality of life. Patient satisfaction significantly correlated with upper limb function. One hand allograft eventually developed severe allograft vasculopathy and was amputated at 7 years. The patient later died due to progressive gastric cancer. The other four patients are currently rejection-free with moderate levels of immunosuppression. Hand transplantation remains a therapeutic option for carefully selected patients. A stable immunologic situation with optimized and individually adopted immunosuppression favors good compliance and patient satisfaction and may prevent development of DSA.

Defining chronic rejection in vascularized composite allotransplantation-The American Society of Reconstructive Transplantation and International Society of Vascularized Composite Allotransplantation chronic rejection working group: 2018 American Society of Reconstructive Transplantation meeting report and white paper Research goals in defining chronic rejection in vascularized composite allotransplantation.

OBJECTIVES: This report summarizes a collaborative effort between the American Society of Reconstructive Transplantation and the International Society of Vascularized Composite Allotransplantation to establish what is known about chronic rejection in recipients of vascularized composite allografts, with an emphasis on upper extremity and face transplants. As a picture of chronic rejection in hand and face vascularized composite allografts emerges, the results will be applied to other types of vascularized composite allografts, such as uterine transplantation. METHODS: The overall goal is to develop a definition of chronic rejection in vascularized composite allografts so that we can establish longitudinal correlates of factors such as acute rejection, immunosuppressive therapy, de novo donor-specific antibody and trauma/infection and other external factors on the development of chronic rejection. As Dr Kanitakis eloquently stated at the 2017 International Society of Vascularized Composite Allotransplantation meeting in Salzburg, "Before we can correlate causative factors of chronic rejection, we have to define what chronic rejection in VCA is." RESULTS: The first meeting report was presented at the sixth Biennial meeting of the American Society of Reconstructive Transplantation in November 2018. Based on collaborative efforts and descriptions of clinical cases of chronic rejection in vascularized composite allograft recipients, a working definition of chronic rejection in vascularized composite allografts with respect to overt functional decline, subclinical functional decline, histologic evidence without functional decline, and normal allograft function in the absence of histologic evidence of chronic rejection is proposed. CONCLUSIONS: It is the intent of this collaborative working group that these working definitions will help to focus ongoing research to define the incidence, risk factors and treatment regimens that will identify mechanisms of chronic rejection in vascularized composite allografts. As with all good research, our initial efforts have generated more questions than answers. We hope that this is the first of many updates.

Erythema Nodosum, Early Stage-A Subcutaneous Variant of Leukocytoclastic Vasculitis? Clinicopathological Correlation in a Series of 13 Patients.

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.

Bar Code Reader - an algorithmic approach to cutaneous occluding vasculopathies? part II medium vessel vasculopathies.

AIMS: Classifications of occluding vasculopathies (except vasculitis [1]) may exhibit some difficulties. Firstly, classifications may follow different principles, e.g. clinicopathologic findings, etiology or pathogenesis. Secondly, authors may not distinguish between vasculitis and occluding vasculopathies. Thirdly, occluding vasculopathies are systemic diseases. Organ-specific variations make morphologic findings difficult to compare. Moreover, subtle changes are recognized in the skin, but may be invisible in other organs. Our aim was to use the skin and subcutis as a tool and clinicopathological correlation as the basic process for classification. METHODS AND RESULTS: We first differentiate in the skin between small and medium vessel occluding vasculopathies. Here we focus on medium vessel-occluding vasculopathies. In the second step we differentiate the vessel subtypes. In the final step, we differentiate according to the time point of the coagulation/reorganization process and the involved inflammatory cells/stromal features. By applying the same procedure to the various entities and visualizing the findings in the style of bar codes, the overlaps and differences in the clinical picture as well as the histopathology become more apparent. CONCLUSIONS: Occluding vasculopathies are often not separate entities, but reaction patterns and epiphenomena. Distinguishing them from vasculitides is crucial because of the differences in pathogenesis, therapeutic approach and prognosis.

Bar code reader - an algorithmic approach to cutaneous occluding vasculopathies? Part I: small vessel vasculopathies.

AIMS: The classifications of occluding vasculopathies may present some difficulties. Firstly, classifications may follow different principles, e.g. clinicopathological findings, etiology or pathomechanism. Secondly, authors sometimes do not distinguish between vasculitis and vasculopathy. Thirdly, vasculopathies are often systemic diseases. Organ-specific variations make morphologic findings difficult to compare. Moreover, subtle changes may be recognized in the skin, but be invisible in other organs. Our aim was to use the skin and subcutis as tools and clinicopathological correlation as the basic process for classification. METHODS AND RESULTS: In the first step, we differentiate between small and medium vessel occluding vasculopathies in the skin, and focus in this part on small vessel occluding vasculopathies. In the second step, we differentiate among subtypes of small vessels. In the final step, we differentiate according to the time point of the coagulation/reorganization process and the involved inflammatory cells/stromal features. Applying the same procedure to the various entities and visualizing the findings with bar codes makes the similarities and differences more apparent, both clinically and with histopathology. CONCLUSION: Occluding vasculopathies are often not separate entities, but reaction patterns and epiphenomena. Distinguishing them from vasculitides is crucial because of differences in pathogenesis, therapeutic approach and prognosis.

Erosive pustulöse Dermatose der Kopfhaut: Neubewertung einer zu wenig beachteten Entität.

Die erosive pustulöse Dermatose der Kopfhaut (EPDK) ist eine entzündliche Erkrankung unbekannter Ätiologie. Wir besprechen die EPDK und präsentieren unsere eigene klinische und histopathologische Erfahrung von elf Patienten. Die EPDK neigt dazu, spontan die kahle Kopfhaut älterer Patienten zu befallen. Anamnestisch wird häufig - so auch bei vier unserer Patienten - eine vorausgegangene Operation an selbiger Stelle angegeben. Koronare Herzerkrankung, cerebraler Insult, arterieller Hypertonus, Diabetes mellitus und ernste Krebserkrankungen wurden ebenfalls häufig als Komorbidität diagnostiziert. Die meisten Patienten zeigen trotz antiinflammatorischer Lokaltherapie einen schwankenden klinischen Verlauf, bei einigen heilt die Läsion unter Narbenbildung ab. Histopathologisch findet sich eine Kruste oder Erosion mit Granulationsgewebe-ähnlichen Veränderungen im Korium mit späterer Entstehung einer Narbe. Neben einer lokalen und aktinischen Schädigung könnten eine eingeschränkte Immunität und Mikrozirkulation prädisponierende Faktoren der Erkrankung sein. Analog zum Pyoderma gangraenosum muss die EPDK bei nichtheilenden Wunden älterer Patienten bedacht werden, nachdem die Differenzialdiagnosen, die diese Erkrankung simulieren, ausgeschlossen wurden. Da vorausgegangene oder benachbarte Basalzell- und insbesondere Plattenepithelkarzinome häufig sind und infiltrative Varianten jenseits des klinisch sichtbaren Krankheitsprozesses vorkommen, kann im Zweifelsfall eine sogenannte histologische Kartierung der umgebenden Haut ratsam sein.

Erosive pustular dermatosis of the scalp: reappraisal of an underrecognized entity.

Erosive pustular dermatosis of the scalp (EPDS) is an inflammatory dermatosis of unknown etiology. Herein, we present a review of the disease and report our own clinical and histopathological experience in eleven patients. EPDS tends to spontaneously affect bald areas of the scalp in elderly individuals. A history of previous surgery at the same site - as observed in four of our patients - is common. Coronary artery disease, cerebrovascular insult, arterial hypertension, diabetes mellitus, and severe cases of cancer were frequent comorbidities. Most patients show an undulating clinical course despite topical anti-inflammatory treatment; in some individuals, the lesions heal with scarring. Histopathology reveals scaly crusts or erosions and granulation tissue-like changes in the dermis, evolving into a scar in more advanced stages. Apart from actinic/local damage, impaired immunity and microcirculation may be predisposing factors of the disease. Similar to pyoderma gangrenosum, EPDS must be considered in the context of nonhealing wounds in the elderly after the differential diagnoses mimicking EPDS have been ruled out. Given that previous or concomitant adjacent basal cell or squamous cell carcinoma is a common finding and that infiltrative variants extending beyond the clinically visible tumor may occur, histological mapping of the surrounding skin may be advisable in doubtful cases.

Annular Lichenoid Dermatitis (of Youth) Immunohistochemical and Serological Evidence for Another Clinical Presentation of Borrelia Infection in Patients of Western Austria.

Annular lichenoid dermatitis of youth (ALDY) is a more recently described inflammatory disease of the skin of unknown etiology with clinical similarities to morphea. The authors clinically, histopathologically, and immunohistochemically investigated 14 biopsies from 12 patients in western Austria with this disease. There were 6 female and 6 male patients with solitary (n = 7) and multiple lesions (n = 5) affecting the trunk (n = 11), upper arm (n = 2), thigh (n = 1), and calf (n = 1). Clinically, early lesions were erythematous in nature leading to central paleness, scaling, wrinkling, dermal atrophy, slight pigmentation, and telangiectasia later on. Histopathologically, all specimens showed the typical features of ALDY with a superficial lichenoid process with sprinkling of lymphocytes along the basal cell layer and within the epidermis accompanied by mild fibrosis. Pigment incontinence, superficial fibrosis, and dilatation of superficial capillary vessels are prominent features in more advanced stages of disease. Immunohistologically, using a polyclonal antibody against Borrelia, 11/14 specimens revealed spirochetes, either vital (n = 4) or degenerated (n = 7), in close proximity to collagen bundles. Thirteen of 14 specimens in addition showed focal (n = 4) or clustered (n = 9) positivity for CD20 in the papillary dermis. Nine of 12 sera tested for Borrelia with an enzyme-linked immunosorbent assay were positive. Lichen sclerosus et atrophicus and morphea have previously been reported to be possibly related to Borrelia infection. We postulate that a similar relationship to Borrelia infection may be true for ALDY implying that ALDY may be an early superficial stage of morphea.