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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.

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.

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.

SummaryBackground Previous classifications of vasculitides suffer from several defects. First, classifications may follow different principles including clinicopathologic findings, etiology, pathogenesis, prognosis, or therapeutic options. Second, authors fail to distinguish between vasculitis and coagulopathy. Third, vasculitides are systemic diseases. Organ-specific variations make morphologic findings difficult to compare. Fourth, subtle changes are recognized in the skin, but may be asymptomatic in other organs. Our aim was to use the skin and subcutis as a model and the clinicopathologic correlation as the basic process for classification. Methods and Results We use an algorithmic approach with pattern analysis, which allows for consistent reporting of microscopic findings. We first differentiate between small and medium vessel vasculitis. In the second step, we differentiate the subtypes of small (capillaries versus postcapillary venules) and medium-sized (arterioles/arteries versus veins) vessels. In the final step, we differentiate, according to the predominant cell type, into leukocytoclastic and/or granulomatous vasculitis. Conclusions Starting from leukocytoclastic vasculitis as a central reaction pattern of cutaneous small/medium vessel vasculitides, its relations or variations may be arranged around it like spokes of a wheel around the hub. This may help establish some basic order in this rather complex realm of cutaneous vasculitides, leading to a better understanding in a complicated field.

Summary Background Angiomatoid fibrous histiocytoma (AFH) is a rare, low-grade malignant, subcutaneous neoplasm in children or young adults. Methods AFHs in different disease stages were studied histologically, in part, also immunohistologically, and by fluorescence in situ hybridization. Results Depending on the degree of fibrosclerosis, nine AFH were divided into the following categories: classic type (n = 3): well-defined subcutaneous lesions composed of multinodular spindle to epithelioid (histiocytoid) cells surrounding a pseudoangiomatous space filled with blood. Peripherally, there is a fibrous pseudocapsule and an inflammatory infiltrate. Early sclerotic type (n = 4): the fibrous capsule extends more to the inner circle of the lesion, focally replacing the cellular neoplastic component and pseudoangiomatous spaces. Late sclerotic type (n = 2): the architecture of AFH with its zonal arrangement of an outer fibrous and inner cellular component is largely replaced by fibrosis occluding the pseudovascular space in the center of the lesion. Immunohistochemistry was available in 5/9 cases with positivity for EMA (5/5), desmin (3/5), caldesmon (1/2), and CD99 (2/5). One of two cases tested displayed EWSR1 rearrangement. Conclusion Late-stage AFH may present with marked fibrosis obscuring the real nature of the lesion and may easily be misinterpreted by the unwary as a harmless fibrotic condition.

Background We herein investigate critical ischemia times and the effect of novel preservation solutions such as new histidine-tryptophan-ketoglutarate (HTK-N) and TiProtec on the individual tissues of a rat limb isograft. Methods Orthotopic hind-limb transplantations were performed in male Lewis rats after 2 hours, 6 hours, or 10 hours of cold ischemia (CI). Limbs were flushed and stored in HTK-N, TiProtec, HTK, or saline solution. Muscle, nerve, vessel, skin, and bone samples were procured on day 10 for histology, immunohistochemistry, confocal and electron microscopy, and quantitative real-time polymerase chain reaction analysis. Results Histomorphology of the muscle showed a mainly perivascular inflammatory infiltrate, fibrotic degeneration, and neovascularization after 6 hours and 10 hours of CI. However, centrally aligned nuclei observed in muscle fibers suggest for muscle regeneration in these samples. In addition to Wallerian degeneration, nerve injury was significantly aggravated (P = 0.032) after prolonged CI. Proinflammatory and regulatory cytokines were most significantly upregulated after 2-hour CI. Our data suggest no superiority of novel perfusates HTK-N and TiProtec in terms of tissue preservation, compared with HTK and saline. Conclusions Limiting CI time for less than 6 hours is the most significant factor to reduce tissue damage in vascularized tissue transplantation. Signs of muscle regeneration give rise that ischemic muscle damage in limb transplantation might be reversible to a certain extent.

Gastrointestinal stromal tumors (GISTs) rarely metastasize to the skin. We describe 5 patients with GIST with subcutaneous and cutaneous metastases. The mean age at metastasis was 54 years (range 30-68 years) with a male predominance (4:1). Primary tumors occurred in the stomach (n = 3), small bowel (n = 1), and abdomen, not otherwise specified (n = 1). The average time from primary tumor resection to the resection of skin metastases was 59 months (range 11-155 months). The metastases occurred in the scalp (n = 2), cheek (n = 1), and abdomen (n = 2) with 3 patients presenting with solitary nodules and 2 patients with multiple nodules. The average size was 2 cm (range 0.6-4 cm). Histologically, 2 cases were spindled and 3 cases demonstrated mixed epithelioid and spindle cell morphology. All were confirmed to have CD117 reactivity. KIT genotyping was performed in 4 of 5 cases. Two cases harbored a mutation in exon 11, and the remaining 2 cases were wild type in exons 9, 11, 13, and 17. All 5 patients had multiple concurrent or subsequent abdominal and/or hepatic metastases. In 4 patients with an average follow-up of 32 months (range 6-75 months), after the resection of the metastases, 2 were alive with disease and 2 died of disease. Cutaneous metastases seem to be a late complication of GIST, but their presence does not necessarily herald a rapid demise of the patient.

Sweet syndrome is a neutrophilic dermatosis defined by diagnostic criteria that include the lack of evidence for leukocytoclastic vasculitis. Because of the clinicopathological similarities on the one hand and the strict exclusion on the other hand, we were interested in a systematic evaluation of the relationship between these two diseases. We investigated the clinical and histopathological characteristics of 31 patients with Sweet syndrome, comparing our cases with 32 cases of leukocytoclastic vasculitis (including seven cases of urticarial vasculitis) and tried to place them in the background of published cases. There is a close relationship between Sweet syndrome and leukocytoclastic vasculitis in terms of clinical appearance, histopathological pattern, triggers, disease course, and response to treatment. The majority of the cases (23/31; 74%) showed histologic evidence of vasculitis, including nuclear dust, extravasation of erythrocytes, fibrin in and around vessel walls, and degeneration of collagen. Although one original criterion for Sweet syndrome is the absence of vasculitis, we propose that vasculitic changes should not exclude the diagnosis of Sweet syndrome. In contrast, Sweet syndrome can demonstrate vasculitis and may, similarly to urticarial vasculitis, be regarded a variant of leukocytoclastic vasculitis. Clinicopathologic characteristics with acute onset of juicy papules, plaques mostly on the face, shoulder, and trunk, and prominent edema probably reflect modifications of the pathogenetic process based on location and disease acuity.

Cutaneous mastocytosis (CM) or urticaria pigmentosa is characterized by abnormal proliferation and accumulation of mast cells. Clinically, CM usually presents as symmetrically distributed red-brown macules or papules that develop weals, erythema and often pruritus on stroking (Darier's sign). The histological hallmark of the disease is an increase in oval to spindle-shaped mast cells in the dermis located around blood vessels and skin appendages. We describe three patients with a new clinicopathological type of CM, which clinically mimics a histiocytic disorder and histologically mimics leucocytoclastic vasculitis (LV). Three infants (two boys and one girl) developed generalized reddish-yellow-brown macules of 3-10 cm with occasional scaling and crusting on the trunk and extremities without further symptoms or organ involvement except variable itching. Histology revealed diffuse and dense dermal infiltrates of eosinophils, neutrophils and nuclear debris with perivascular accentuation, imitating LV. This infiltrate masked large epithelioid cells, positive for macrophage markers, which by special histochemical stains for metachromatic granules turned out to be mast cells. This is the first report of this new variant of CM, which may cause considerable diagnostic difficulties both clinically and histopathologically.

Teratocarcinosarcoma (TCS) is a very rare and aggressive neoplasm characterized by teratoma and carcinosarcoma components. The authors report on a case of TCS in the oral cavity of a child. Rapid growth and extensive local destruction were prominent features prior to treatment. Histologic examination revealed various tissue elements, such as epithelial, mesenchymal, and neuroectodermal components. Chemotherapy was effective in reducing tumor mass, followed by partial anterior mandibulectomy and reconstruction with composite microvascular tissue transfer. The approach allowed radical resection of the tumor and functional reconstruction with excellent aesthetic results.

Atypical cutaneous fibrous histiocytoma is a rare variant of dermatofibroma/fibrous histiocytoma characterized by striking atypia, thus resembling atypical fibroxanthoma. We studied 9 examples of ACFH histopathologically and immunohistochemically to investigate the nature of these atypical cells. Histology revealed ill-defined skin nodules, which were polypoid in 6 cases. A minority of mononuclear and giant cells (< 5%) revealed striking pleomorphism and showed large nuclei with prominent nucleoli. Immunohistologically, the atypical cells expressed vimentin, but were negative for S-100 protein, the keratin marker MNF116, alpha smooth muscle actin, CD34, factor XIIIa, and monocyte/macrophage markers Ki-M1p, KP1 (CD68), and MAC387. Positivity for MiB1 was very modest (< 1%) and limited to small- and medium-sized, inconspicuous cells. Multinucleate giant cells proved to be heterogenous, on one hand cells with differentiation toward macrophages with positivity for Ki-M1p and KP1, on the other toward fibroblasts positive for vimentin only. These immuno-histochemical results for differentiation markers in atypical cutaneous fibrous histiocytoma are similar to our previous findings and data in atypical fibroxanthoma; MiB1 helps to separate these entities from each other as the latter shows a very high proportion of proliferative atypical cells corresponding to the numerous mitoses seen in routine sections.

Two patients with metastatic melanoma, both with the same bizarre morphology and an unusual, comparatively benign course, are described: a 50-year-old female who more than 20 years after a primary melanoma on the right upper arm, Clark level III, maximum tumor thickness of 1.1 mm, developed multiple metastases in the deep soft tissue and a 62-year-old male with an acrolentiginous melanoma, Clark level III, maximum tumor thickness of 0.55 mm, who 6 months after the excision of the primary tumor developed metastasis in regional lymph nodes. Histology of all metastases revealed extensive central necrosis and hemorrhage with a demarcating granulomatous reaction imitating angiomatoid malignant fibrous histiocytoma but no obvious melanoma tissue. Although extensive immunohistochemistry and ultrastructural examination failed to solve the quandary, careful macroscopy revealed tiny foci of remnants from melanoma in the granulation center. The female developed multiple soft tissue metastases managed by surgery, immunochemotherapy, and autologous vaccination. Both patients are well without internal manifestations 9 and 5 years, respectively, after the first metastatic episode.

Summary Background: Clear cell melanoma is a recently described variant of melanoma characterized by prominent clear cell features similar to clear cell sarcoma. Patients and methods: The present report describes a deeply invasive case of clear cell melanoma clinically, histologically, immunohistochemically, ultrastructurally and with the FISH technique and compares these findings with those in clear cell sarcoma. Results: A 68-year-old male presented with an ulcerated, deeply invasive melanoma on the heel, corresponding to Clark level V, with a maximum tumour thickness of more than 14 mm; follow-up revealed inguinal lymph-node and lung metastases. Apart from characteristic histological features of melanoma with intraepidermal involvement, the lesion was immunohistochemically positive for S100 protein, with HMB45 and A103 (anti-human Melan-A/MART-1), and ultrastructurally showed melanosomes. In deeply invasive parts, the lesion was indistinguishable from clear cell sarcoma, exhibiting nests, fascicles and sheets of pale-staining epithelioid to spindle-shaped cells (‘clear cells’) with scattered Touton-like multinucleated giant cells. Cytogenetic analysis using the FISH technique revealed a 12q13 chromosomal break in the vicinity of the ATF1 gene but without ATF1 disruption. Conclusion: These findings may indicate the possible involvement of the ATF1 gene in clear cell melanoma tumorigenesis, similar to clear cell sarcoma with classical t(12;22) translocation. Zusammenfassung Hintergrund: Klarzellmelanome sind eine kurzlich beschriebene Variante eines Melanoms, gekennzeichnet durch ausgepragte Klarzellveranderungen mit Ahnlichkeiten zum Klarzellsarkom. Patienten und Methodik: Vorliegende Arbeit beschreibt einen Fall von Klarzellmelanom klinisch, histologisch, immunhistochemisch, ultrastrukturell und mit FISH-Technik mit detailliertem Vergleich zum Klarzellsarkom. Ergebnisse: Ein 68-jahriger Mann prasentierte sich mit einem exulzerierten, tief invasiven Melanom, Clark level V, maximale Tumordicke groser als 14 Millimeter, an der Ferse; im Verlauf traten inguinale Lymphknoten- und Lungenmetastasen auf. Abgesehen von charakteristischen Veranderungen eines Melanoms mit intraepidermaler Beteiligung war die Lasion immunhistochemisch positiv fur S100-Protein und mit HMB45 und A103 (anti-humanes Melan-A/MART-1) und zeigte ultrastrukturell Melanosomen. In tief invasiven Abschnitten war die Lasion ununterscheidbar von einem Klarzellsarkom mit Nestern, Faszikeln und diffusen Infiltraten von blas gefarbten, epithelioiden bis spindelformigen Zellen („Klarzellen”) mit vereinzelten toutonartigen Riesenzellen. Zytogenetische Untersuchungen mit FISH-Technik zeigten einen 12q13-Chromosomenbruch in der Nahe des ATF1-Gens, aber ohne Aufsplitterung dieses Gens. Schlusfolgerung: Diese Veranderungen weisen moglicherweise auf die Mitbeteiligung des ATF1-Gens bei der Entstehung des Klarzellmelanoms hin, ahnlich dem Klarzellsarkom mit seiner klassischen t(12;22) Translokation.

Background: Papular xanthoma (PX) is one of several clinicopathologic variants of normolipemic cutaneous non-Langerhans cell histiocytoses (n-LCH). PX represents a monomorphous reaction pattern of n-LCH characterized by the presence of predominantly xanthomatized macrophages. Objective: The purpose of this study was to identify the clinical, histological and immunohistochemical characteristics of PX. Methods: A series of 10 cases of PX was identified and the results compared with the other histologic subtypes, namely the polymorphous and the remaining other monomorphous reaction patterns in n-LCH. Results: In this clinicopathologic study, papular xanthoma presented clinically mainly as solitary papule, with a male to female ratio of4 : 1, in an age range from 13 to 57 years and a biphasic occurrence: in the young adolescence and middle ages. It was predominantly located on the trunk, the extremities, and rarely on the head. Clinically, PX was described as xanthoma, ‘cutaneous tumor’, but also as atheroma, keloid, histiocytoma, Spitz's nevus or clear cell acanthoma. Histology showed moderately well circumscribed exoendophytic papules with a regular epidermis and a dense infiltration of xanthomatized macrophages interspersed by numerous Touton type giant cells. Immunohistochemically mono- and multinucleated macrophages were consistently positive with KiM1p; while only giant cells were labeled with KP1 (CD68), the reactivity with HAM 56 was much more variable. Up to 50% of the xanthomatized cells labeled positive for the lectin peanut agglutinin. In one case the xanthomatized cells stained positive for CD34. Staining for factor XIIIa and CD1a were negative. Conclusions: This series confirms PX as a rare, but distinguished clinicopathologic entity in the spectrum of n-LCH of the skin.

Aims: Based on a series of 25 cases, we define and characterize combined dermatofibroma, a tumour comprising two or more variant patterns of dermatofibroma in a single lesion. Method and results Dermatofibroma may present with a wide variety of architectural, cellular or stromal peculiarities. Architectural peculiarities include deep penetration, atrophy, collarette formation, fascicular to plexiform architecture, massive haemorrhage, prominent haemangiopericytoma-like vascularity and palisading; cellular peculiarities the presence of epithelioid cells, clear cells, granular cells, prominent myofibroblastic differentiation and atypical giant cells (‘monster cells’); or stromal peculiarities such as prominent sclerosis, mucin, haemosiderin and cholesterotic deposits. In combined dermatofibromas two or more of these features are seen in complex or inhomogenous combination such as the silhouette of a deep penetrating dermatofibroma with an ‘ordinary’ storiform pattern in the upper and granular cell differentiation in the lower part of the lesion; or a dermatofibroma with ordinary features in the upper, prominent sclerosis in the middle and clear cells in the lower portion of the lesion; or the characteristic epidermal collarette and cells of epithelial cell histiocytoma with a plexiform (‘neurothekeoma-like’) architecture surrounded by a myxoid stroma with spindle-shaped to stellate cells. Clinically, these lesions preferentially occur on the lower extremities of young to middle-aged females, frequently with the diagnosis of a fibrohistiocytic lesion. Apart from one recurrence follow-up was uneventful in all other cases. Immunohistochemically, lesions are consistently positive with KiM1p, variably positive for factor XIIIa, smooth muscle specific actin and with KP1 (CD68), NK1C3 and E9. Conclusion Recognition of combined dermatofibroma allows the histopathologist to apply a confident benign label to unusual lesions which might otherwise elude diagnosis, or tempt description of ‘new’ entities and to avoid a misdiagnosis of malignancy.

Aims: We describe nine cases of scalloped cell xanthogranuloma, a distinct solitary variant of non-Langerhans cell histiocytoses. Methods and results: In this retrospective clinicopathological study scalloped cell xanthogranuloma mostly occurred on the back or head and neck of young adult males diagnosed as a xanthogranuloma, naevus, or basal cell carcinoma. Histology characteristically revealed a sheet-like infiltrate of predominantly scalloped histiocytes (> 75% of all cell types) in the upper dermis. Other mononuclear (vacuolated, xanthomatized, spindle-shaped, oncocytic) and multinucleate (foreign body, ground glass and Touton) histiocytes were also regularly seen. Immunohistochemically, all cases exhibited a macrophage/dendritic cell lineage positive with KP1 (CD68), KiM1p, HAM 56 and factor XIIIa. Ultrastructurally, numerous intracytoplasmic dense, occasionally also myeloid bodies were present. No associated systemic disease, hyperlipidaemia or recurrence were seen during follow-up. Conclusions: These findings are similar to those of early lesions of xanthoma disseminatum; thus, scalloped cell xanthogranuloma could be regarded as a solitary counterpart of xanthoma disseminatum, and, moreover, fits neatly into a unifying concept of non-Langerhans cell histiocytoses.

Metallothioneins (MTs) are metal binding proteins overexpressed in various human neoplasms which are associated with resistance to cytotoxic drugs. A series of 156 archival human brain tumours were investigated immunohistochemically for expression of MTs; these included 10 low-grade gliomas, 44 high-grade gliomas, 98 meningeal tumours (19 classical, 30 atypical, 38 anaplastic meningiomas, and 11 haemangiopericytomas or papillary meningiomas), and 4 other tumours. Low-grade gliomas showed heterogeneous MT expression; 32 high-grade gliomas (72.7%) showed MT expression of more than 25% of tumour cells without statistically significant differences between first operations and recurrent tumours. In 2 glioblastomas, the presence of MT was confirmed by Western blotting. The extent of MT immunoexpression showed a statistically significant inverse relationship to the degree of p53 immunoreactivity. In meningiomas, a tendency to a higher percentage of MT-expressing cells was observed from classical over atypical to anaplastic meningiomas, but these differences were not statistically significant. In conclusion, MT expression is present in a significant portion of, especially malignant, brain tumours and might be involved in their poor response to antineoplastic drugs.

We report the unusual history of a young lady who, over a period of 9 years, developed 3 epithelioid neoplasms of different histiogenetic origin: a cutaneous epithelioid hemangioendothelioma, an epithelioid cell histiocytoma, and a Spitz nevus. To the best of our knowledge, such an unusual combination of neoplasms has not been reported previously and raises the question of an underlying "epithelioid" reaction pattern responsible for the epithelioid appearance in all 3 tumors; the likelihood of such a combination of tumors occurring in a single patient would be less than 1 in 1 billion.

We report on eight cases of a distinct variant of cutaneous schwannoma characterized by prominent Verocay body formation (75-100% of the tumor bulk) that may cause considerable diagnostic difficulties. Like ordinary cutaneous schwannomas, these lesions preferred the head and neck region of young adults without sexual predilection and were clinically interpreted as cyst, basal cell carcinoma, or nevus. Histological examination revealed well-circumscribed nodules. Three of them consisted exclusively of nodular or ribbon-like Verocay bodies. A variable admixture of Antoni A or B type of differentiation (< 25%) was seen in five other cases. The following patterns were seen: fascicular spindle-shaped, onion-like epithelioid, myxoid-hypocellular, and degenerated ("ancient") with prominent fibrosis/hyalinosis and occasional bizarre giant cells. Immunohistochemically, the lesions were positive for S-100 protein (and vimentin) but negative for a broad panel of neurogenic and intermediate filament markers. The capsule showed focal labeling for EMA and--when it was markedly thickened--also for SMA. Labeling with E9, an anti-metallothionein marker indicative of cell activity, was negative, underscoring the slow growth potential of these lesions. No recurrence was seen in the six patients with follow-up information. The differential diagnosis includes other lesions with prominent palisading. (Amianthoid) myofibroblastoma and palisading leiomyoma are consistently positive for SMA and desmin, respectively. Palisading cutaneous fibrous histiocytoma and myofibroblastic dermatofibroma are variably positive for Factor XIIIa, SMA, and E9 and/or NK1C3 (CD57). Palisaded encapsulated neuromas are primarilly differentiated by the presence of nerve fibers with myelin sheaths.

An extranodal high-grade B-cell lymphoma, centroblastic type, with exclusive involvement of the heart, stomach and small bowel was detected at post-mortem examination following the death of an 80-year-old man. Autopsy revealed massive cardiomegaly with a total heart weight of 1800 g owing to an intramyocardial tumour involving the right ventricle, and multiple mucosal tumour plaques and nodules in the stomach and small bowel. The case highlights the difficulties of diagnosing cardiac lymphoma clinically even in the presence of a large tumour mass.

We report five cases of plexiform fibrohistiocytic tumors, three classic subcutaneous lesions and two dermal ones. Both variants had similar profiles and were clinically indistinguishable. The lesions affected the trunk more than the upper extremities and were found in children and young adults (18.4 +/- 12.8 years). They showed a marked female predominance (4:1, including both dermal variants). Clinically, they were skin-colored, hard nodules of 1-2-cm diameter that resulted in such differential diagnoses as fibroma, histiocytoma, pilomatricoma, or cyst. Interestingly, one subcutaneous case with a painful "worms in the sack" presentation was thought to represent a plexiform neurofibroma. Histology revealed well-circumscribed dermal or subcutaneous plexiform lesions with a characteristic biphasic appearance. Most of the tumor bulk consisted of spindle-shaped to stellate myofibroblasts with a variable admixture of collagen or loosening of stroma. In the center of the plexiform strands and nodules, a few osteoclast-like giant cells as well as epithelioid mononuclear cells (< 10%) were found. Myofibroblasts were positive with HHF35 and for smooth muscle actin in three of five cases. Osteoclast-like giant cells were positive with KP1 in all five cases. Both types of cells stained with the macrophage marker Ki-M1p. A broad panel of other markers was negative. This series expands the spectrum of plexiform fibrohistiocytic tumor, but it also broadens the differential diagnosis of (dermal) plexiform lesions, which at present includes spindle cell nevi, schwannomas, neurofibromas, granular cell tumors, nerve sheath myxomas (neurothekeomas), spindle cell lipomas, and tufted angiomas.

This series presents six cases of a rare variant of dermatofibroma, characterized by marked clear cell change. All lesions occurred on the lower extremities of middle-aged adults (four women, two men), mostly with the clinical diagnosis of fibrohistiocytic lesion. Histological examination revealed well circumscribed, faintly stained dermal to subcutaneous lesions which were due to the overwhelming presence of clear cells (> 90%), some with prominent PAS-positive cytoplasmic granulation. Overlying epidermal hyperplasia as well as storiform arrangement of spindle cells, sclerotic collagen and some interspersed lympho-histiocytic infiltrate at the periphery of the lesion indicated the fibrohistiocytic origin. Individual histopathological peculiarities included: bizarre giant cells in two cases, perifollicular arrangement and haemangiopericytoma-like features with iron deposition in one case each. Immunohistochemically three of four lesions showed moderate reactivity for factor XIIIa and two of four with an anti-metallothionen marker E9, but were otherwise negative with a broad panel of markers. Electronmicroscopy in two cases revealed large pools of glycogen beside focal, prominent endoplasmic reticulum and lysosomes in some granular cells, but only optically translucent cells in cases of clear cells. Recognition of clear cell dermatofibroma is important as the differential diagnosis includes some entities with more serious outcome/considerations such as metastases of renal cell carcinoma, xanthogranulomatous reactions, balloon cell naevus/melanoma and clear cell sarcoma.

We report on our histological experience in 47 patients with lichen planopilaris/frontal fibrosing alopecia. Besides presenting the spectrum of clinical appearance of the disease we emphasize the importance of vertical histologic sections of biopsies in the clinicopathological work-up of these patients and give precise histologic criteria and clues in different stages of the disease. Immunohistologically, we found a marked reduction of epithelial Ki-67 expression next to the inflammatory process especially evident in advanced stages of disease.

An otherwise healthy 50-year-old woman presented with a 6-month history of having developed more than 100 generalized, non-confluent, reddish-brown, partially yellow-coloured papules. A non-epidermotropic, monomorphous infiltrate of vacuolated mononuclear, and occasionally multinuclear, histiocytes, positive for factor XIIIa and macrophage markers HAM56 and KiM1p, was consistent with the clinical impression of generalized eruptive histiocytomas. However, the additional reactivity for S100 protein, in the absence of features of histiocytosis X, suggested a diagnosis of indeterminate cell histiocytosis (ICH). Further immunohistochemical studies, performed on snap-frozen material, characterized the lesions as being diffusely positive with LN3 (HLA-DR), Leu4 (CD3) and Leu3 (CD4), the infiltrate in the upper dermis as reactive for OKT6 (CD1) and IOT6c (CD1c), and the infiltrate in the lower dermis as reactive for a variety of macrophage markers. Ultrastructural studies showed various non-specific features of histocytic disorders, but no Birbeck granules. Our findings confirm those of previous reports suggesting that ICH is a distinct histiocytic entity, characterized by immunophenotypic features of both X- and non-X histiocytoses. Generalized eruptive histiocytoma seems to be an early indeterminate stage of various non-X histiocytic syndromes including ICH, multicentric reticulohistiocytosis, xanthogranuloma and xanthoma disseminatum. The distribution pattern of the various X/non-X histiocytic markers suggests dermal arrest of antigen-presenting cells during their physiological trafficking from the skin to the lymph nodes.

We report a 48-year-old woman with a pleural pseudoneoplasm requiring different diagnostic and therapeutic strategies. After initial presentation with increasing dyspnoea, temperature, dry cough, and interscapular pain diagnostic processing showed a large mediastinal mass with marked pleural effusion and high metabolic activity in the 18F-FDG-PET/CT. Extensive CT-guided biopsy of the tumor reaching from the visceral pleura into the right upper lobe revealed no malignancy, but a marked inflammatory tissue reaction containing foam cells. Initial empiric antibiotic therapy was temporarily successful. However, in the further course the mass relapsed and was resistant to antibiotics and a corticosteroid trial. With the working hypothesis of an inflammatory myofibroblastic tumor the patient underwent surgical tumor resection, finally confirming the suspected diagnosis. Due to residual disease intravenous immunoglobulins were administered leading to sustained response. This case with a pleural localisation of a large inflammatory pseudotumor with responsiveness to immunomodulation after incomplete resection extends the reported spectrum of thoracopulmonary manifestations of this rare entity.

The so called 'sweat gland carcinoma' is a rare skin malignancy. The differentiation between apocrine and eccrine neoplasms remains difficult. Skin tumors of the axilla are often suspected to be metastasis of other neoplasms in particular breast cancer. A 71-year-old man presented with a morphea-like plaque of the right axilla which in punch biopsy was first suspected as metastasis of primary lobular breast carcinoma. After further clinical and laboratory work up including immunohistochemistry the original diagnosis of a breast cancer had to be changed to solid apocrine carcinoma of the skin. Wide excision with en-bloc axillary lymph node dissection was performed. Final tumor stage was pT2 N0 M0 (V0 L0). No adjuvant treatment was necessary, and there is no evidence of disease after 3 years. Solid apocrine carcinoma of the skin is a rare variant with apocrine differentiation. A survey of the stereotypical presentation of this lesion and a comparison with lobular breast carcinoma and other types of apocrine carcinoma of the skin is given.

Background Primary sarcoma of the gallbladder (PGBS) is rare, with only 40 cases reported in the literature. Most of these have been diagnosed as leiomyosarcoma. We aimed to evaluate the histological features of a case series of this rare tumor and correlate these with clinical features. Design Cases recorded as “gallbladder sarcoma” from different institutes were reviewed and the clinicopathological features of these cases were recorded. Only primary gallbladder wall mesenchymal tumors were included. Epithelial tumors, mixed tumors (carcinosarcoma or sarcomatoid carcinoma), and tumors extending into the gallbladder from the abdomen or sarcoma with other known primaries were specifically excluded. Result PGBS occurred in one male and six females with a median age of 70 (range 64–82) years. Patients presented with acute or chronic cholecystitis, abdominal pain, weight loss, and pruritis. They were generally found to have elevated alkaline phosphatase and bilirubin, and leukocytosis. Tumors ranged from 1.1 to 4 cm with a median size of 3 cm. Most PGBS arose in the body but one arose in the fundus. All tumors were associated with ulcerated mucosa. Based on morphological and immunohistochemical features of the PGBS, there were three myxofibrosarcomas (malignant fibrous histiocytoma, MFH, storiform pleomorphic), one leiomyosarcoma (LMS), one angiosarcoma (AS), and two liposarcomas (LS). All patients received cholecystectomy and three received adjuvant chemotherapy. Follow-up revealed that six patients died of the disease 6 weeks to 2 years after diagnosis and one died of unrelated causes. Conclusion PGBS are rare and mainly occur in the gallbladder body in middle-aged females. They generally present with acute cholecystitis and have a very poor prognosis. A variety of sarcoma types are found with MFH being the predominant variant.

Echinococcosis, also known as hydatid disease, is an infection of larval stage animal tapeworm, Echinococcus. The larvae reside in the liver and lungs, producing multiloculated fluid-filled cysts. Imaging findings of Echinococcosis caused by E. granulosus are single, unilocular cyst or multiseptated cysts, showing “wheel-like”, “rosette-like” or “honeycomb-like” appearances. There may be “snow-flakes” sign, reflecting free floating protoscoleces (hydatid-sand) within the cyst cavity. Degenerating cysts show wavy or serpentine bands or floating membranes representing detached or ruptured membranes. Degenerated cysts show heterogeneous, solid-looking pseudotumor that may show “ball of wool sign”. Dead cysts show calcified cyst wall. Echinococcosis caused by E. multilocularis produces multilocular alveolar cysts with exogeneous proliferation, progressively invading the liver parenchyma and other tissues of the body. Imaging findings are ill-defined infiltrating lesions of the liver parenchyma, consisting of multiple small clustered cystic and solid components. On sonography, lesions are heterogeneous with indistinct margins, showing “hailstorm appearance” or “vesicular or alveolar appearance”. CT and MR imaging displays multiple, irregular, ill-defined lesions. Multiple small round cysts with solid components are frequent. Large lesions show “geographical map” appearance. Calcifications are very frequent, appearing as peripheral calcification or punctuate scattered calcific foci. Invasion into the bile ducts, portal vein or hepatic vein may occur. Direct spread of infected tissue may result in cysts in the peritoneal cavity, kidneys, adrenal gland or bones.

Dermatofibromas are common cutaneous lesions. In most cases, they can be readily identified clinically and show a typical histology. In a small percentage of cases they show unusual clinical and more often histologic features that may cause differential diagnostic problems. In addition there are reactive fibrous lesions with neural or smooth muscle features that we speculate may represent dermatofibroma variants.

We report on three exceptional courses of sinus histiocytosis Rosai-Dorfman. Patient one developed regional lymph-node disease subsequent to two independent malignancies in the right head and neck region. Patient two suffered from extensive extranodal disease with more than 100 mucocutaneous lesions over 17 years, which spontaneously resolved. Patient three showed exclusively extranodal disease, including bilateral conjunctival/scleral lesions, before he developed lung cancer. Our cases are unique for three reasons: the association of the disease with solid malignancies in two cases, the extent and persistence of exclusively extranodal disease in one patient and the appearance of thus far undescribed conjunctival/scleral lesions.

Pleomorphic fibroma (PF) and dermatofibroma with monster cells (DFMC) are characterized by the presence of numerous cells with large atypical nuclei. Despite cytologic similarities, the two entities are likely to be unrelated, but their histogenesis is poorly understood. In this study, we examined six cases of PF and eleven cases of DFMC by immunohistochemistry using antibodies against vimentin, alpha-smooth muscle actin, S-100 protein, CD34, factor XIIIa, and the pan-monocytic marker Ki-M1p. Strong vimentin expression was seen in all tumors, whereas none of them expressed S-100 protein. PF consistently exhibited CD34 staining but appeared to be depleted of Ki-M1p positive cells compared with the surrounding normal skin. Conversely, all cases of DFMC contained numerous Ki-M1p positive cells including atypical multinucleate cells, but virtually no CD34 reactivity was observed. A weak staining for alpha-smooth muscle actin was occasionally seen in a subset of the cells of both entities. Our results indicate that PF and DFMC are histogenetically distinct entities that may arise from two different types of dermal dendritic cells defined by their reactivity for CD34 and Ki-M1p, respectively. Immunohistochemistry using these two antibodies permits an easy and reliable discrimination between PF and DFMC.

Aims Cellular neurothekeoma is a rare benign cutaneous neoplasm with conflicting opinions regarding its histogenetic origin (nerve sheath, smooth muscle, myofibroblasts) as well as its relation to myxoid neurothekeoma (nerve sheath myxoma). The present series describes 15 cases whose clinicopathological features indicate a relationship to dermatofibroma. Methods and results In this retrospective clinicopathological study, the lesions preferentially occurred in adolescents to young adults on the upper half of the body, often clinically diagnosed as some kind of fibrohistiocytic tissue response. Besides characteristic whorled nests to fascicles of palely eosinophilic epithelioid cells, all lesions showed variable clues pointing to dermatofibroma: acanthosis, ill-defined storiform periphery, peripherally accentuated prominent sclerosis and lymphocytic demarcation/infiltration. Immunohistochemically, all cases were positive with NK1C3 (CD57), KiM1p and proliferating cell nuclear antigen, seven were positive for neurone specific enolase, five for factor XIIIa, six for smooth muscle specific actin and three for E9, an antimetallothionein marker. These findings are similar to those of conventional dermatofibromas, the variability of the profile being best explained by time cycle and function dependent changes. Ultrastructurally, two cases showed microfilaments, attachment plaques, prominent pinocytosis and focal remnants of basal lamina. A careful study of the data and photomicrographs from the literature reveals that in many cases similar conclusions could be reached. Obvious discrepancies are most likely due to the confusion with myxoid neurothekeoma, a well circumscribed, more spindly and myxoid, S100 positive lesion of Schwannian origin. Conclusion The appearance of dermatofibromas is markedly influenced by architectural, e.g. in deep penetrating dermatofibroma, and/or cellular/stromal criteria, e.g. in epithelioid cell histiocytoma or sclerosing dermatofibroma. Cellular neurothekeoma seems to be a variant of dermatofibromas with both architectural and cellular/stromal peculiarities, i.e. plexiform pattern, epithelioid cytology and stromal sclerosis.

background Primary malignant melanomas, recurrences, and metastases thereof can present with a wide variety of clinicopathologic aspects. objective The present series describes eight primary malignant melanomas and/or 10 local recurrences/metastases (from eight patients) misdiagnosed as various types of soft tissue tumors: two dermatofibrosarcoma protuberans, two atypical fibroxanthomas, rim storifoirmplcomorphic malignant fibrous histiocytomas, one myxofibrosarcoma (“myxoid malignant fibrous histiocytoma”), two malignant hemangiopericytomas, and nine malignant schwannomas. methods In three cases correct diagnosis was established by clinicopathologic correlation during follow-up; all the others were only discovered during a retrospective work-up of all soft tissue tumors diagnosed at the Dermatohistopathological Laboratory of the Department of Dermatology, University of Innsbruck. results Helpful clues derived from subtle intraepidermal, irregular spread of melanocytes, focal nested arrangement of tumor cells, sparse melanin deposition, neurotropism, and prominent peripheral lymphohistiocytic response, partially forming lymph follicles. Besides clinicopathologic correlation, histology of serial sections as well as iminunohistodiemistry (S100 protein more important than NK1/C3; HMB45 without benefit) and electron microscopy (melatiosomes) proved helpful for definitive diagnosis. In contrast to the general assumption that spindle cell/desmoplastic malignant melanomas have an unequivocal bad prognosis, our series, as well as evidence from the literature, document a better prognosis than that of other types with comparable tumor thickness (70% us 50% 5-year survival). Moreover, labeling with E9, an antimetallothionein marker, confirmed its usefulness for prognosis being strongly positive in primary lesions followed by rapid progression, but mostly negative in those without. conclusion These cases document that malignant melanoma may mimic various types of soft tissue tumors; correct interpretation is important as prognosis and therapeutic management differ considerably between these entities.

Aims We report a series of five unusual subcutaneous lipomas characterized by prominent stromal sclerosis in a storiform arrangement. Methods and results All lesions occurred in young male adults (23.0 +/- 9.5 years), three lesions were on the scalp and two on the hands. Clinically, lipoma, chondroma or some form of cyst were suspected. In contrast to sclerotic fibroma ('circumscribed storiform collagenoma') a variable number of adipocytes were interspersed within the fibrosclerotic background. These cells also showed immunoreactivity for S100 protein as well as intracytoplasmic lipid deposits ultrastructurally. None of the lesions recurred within a follow-up period of between 0.5 and 9 years. Conclusions Our series suggests that sclerotic lipomas should be classified with fibro- and myxolipomas, angiolipomas, spindle cell and pleomorphic lipomas, as an additional characteristic subtype of lipoma. Sclerotic lipomas are often misdiagnosed as a sclerotic fibroma, but are essentially fatty tumours and are, at least in our small series, not associated with Cowden's disease.

We report on eleven cases of a distinctive dermal spindle cell lipoma characterized by a mixture of mature adipocytes and spindle-shaped cells in a fibromucinous background. Six lesions showed a moderately well circumscribed plexiform pattern, five a well demarcated nodular pattern with compression of surrounding connective tissue and prominent stromal fibrosis. Clinically, the plexiform type mostly occurred in the thigh-groin-buttock area and the nodular type in the head-neck or acral location. While plexiform lesions were predominantly seen in middle-aged females, nodular types occurred in young adults of either sex. No recurrence was seen in five patients with follow-up. The tumour cells were vimentin positive and a thin cytomplasmic rim of S-100 protein positivity was seen in mature adipocytes. Ultrastructural studies revealed lipoblastic differentiation of spindle-shaped cells with lipid droplets and basal lamina formation. Dermal spindle cell lipomas seem to be the dermal counterpart of the most subcutaneously located spindle cell lipoma.

Dermal atrophy of more than 50% of the locoregional dermis may be the predominant histopathological feature in dermatofibroma and dermatofibrosarcoma protuberans. This may cause diagnostic difficulties. In the present study 26 cases of atrophic dermatofibroma were compared with three cases of atrophic dermatofibrosarcoma protuberans. Clinically, both conditions mostly occurred on the (upper) trunk of females. While atrophic dermatofibroma usually presented as a reddish, umbilicated lesion (0.5-1cm), often suspected to be a basal cell carcinoma, atrophic dermatofibrosarcoma protuberans showed irregularly arranged tan-brown plaques (3-6 cm). Histologically, atrophic dermatofibroma showed a regular silhouette with a smooth nodular (9/26) or scalloped lower margin with an intervening lace-like pattern of superficial fatty tissue infiltration (17/26) and variable sclerosis: atrophic dermatofibrosarcoma protuberans showed a deep, irregular infiltration of fatty tissue in a lacelike/honeycomb and/ or multilayered pattern, but no sclerosis. Immunohistochemically, atrophic dermatofibroma was mostly negative with QBEnd 10 (CD34;24/26), variably positive for factor XIIIa (20/26) and metallothionein (11/26). Labelling for factor XIIIa and metallothionein was usually seen in 'early' (metabolically active) lesions, while 'late' sclerotic ones were negative. In contrast to atrophic dermatofibroma all three atrophic dermatofibrosarcoma protuberans showed a consistently uniform profile: CD34 positive, factor XIIIa and metallothionein negative. Our study delineates atrophic dermatofibroma and atrophic dermatofibrosarcoma protuberans as distinct entities clearly distinguishable from each other by clinicopathologic criteria.

Infantile myofibromatosis (IMF) is a distinct clinicopathologic entity characterized by solitary or multicentric tumors present at birth or in early infancy with a typical biphasic (central hemangiopericytoma-like, peripheral leiomyoma-like) histologic pattern. We present a case of IMF in two siblings with onset of disease in late childhood. Histology of the primary as well as several later tumors was characterized by a monophasic cellular appearance with a prominence of tiny capillaries initially suggesting an unusual vascular tumor. Diagnosis was established by the development of more characteristic biphasic lesions during the course of disease. Immunocytochemistry (Ulex, factor VIII, JC/70A [CD31], PAL-E, BMA120, EN4, QBEnd10 [CD34], SMS actin) and ultrastructural studies showed no (marked) differences between different types of IMF. The monophasic cellular pattern should be recognized as an unusual histologic manifestation of IMF, in particular in patients outside the classical setting or presentation.