Generalized Eruptive Histiocytoma With S100 Protein-Positive Histiocytes and Prominent Eosinophilic Infiltration: A Rare Case Report.

ABSTRACT: Generalized eruptive histiocytoma (GEH) is a very rare benign disorder belonging to the group of non-Langerhans cell histiocytosis (non-LCH). GEH is characterized by a nearly uniform infiltrate of histiocytes with classic immunological phenotype (CD68+, S-100- and CD1a-). Prominent eosinophilic infiltration and S100-positive histiocytes are rarely associated in GEH. In this article, we reported a middle-age man presented with disseminated reddish papules distributed on the trunk and proximal extremities. A skin biopsy of the papule showed a dense histiocytic infiltration with prominent eosinophils. By immunohistochemistry, the histiocytes revealed strongly positive for CD68 and S100 protein and negative for CD1a and Langerin (CD207). Based on clinical and histopathological criteria, the diagnosis of GEH was established. We presented this rare case of GEH with such distinctive features to strengthen the awareness of this uncommon form of non-LCH. Classical histopathological and immunological features cannot reliably distinguish GEH from other non-LCH.

Invasive histiocytoma in the ear canal of a dog.

BACKGROUND: Cutaneous histiocytomas (CH) are derived from epidermal Langerhans cells. Single CH are generally associated with a good prognosis in dogs because most undergo spontaneous remission. However, aggressive behaviour and lymph node metastasis have been reported in a small number of dogs with single CH. OBJECTIVE: To describe the clinical presentation, treatment and disease progression of an aggressive CH located in the ear canal of a dog. ANIMAL: An 8-year-old intact male Rottweiler dog. METHODS AND MATERIALS: A unilateral ear canal mass was identified as a CH on routine haematoxylin and eosin stained samples. The diagnosis was confirmed by the demonstration of markers associated with Langerhans cells (Iba-1, E-cadherin and CD18) and the absence of markers associated with B cells (CD79a, CD20, Pax5), T cells (CD3), plasma cells (Mum-1) and macrophages (CD11d, CD204). RESULTS: A total ear canal ablation was performed, but tumour cells extended throughout the horizontal canal and to the deep surgical margin. Due to the locally invasive nature of the mass and incomplete excision, adjunctive chemotherapy with CCNU was pursued. No measurable local disease was appreciable at the time of the last treatment. At 250 days post-surgery the dog was euthanized owing to the development of multiple abdominal masses. No evidence of local tumour recurrence was noted. CONCLUSIONS AND CLINICAL IMPORTANCE: Although single CH are typically associated with benign behaviour, the mass in this dog demonstrated locally invasive behaviour. Cutaneous histiocytomas in the ear canals of dogs may represent a particularly aggressive variant of the condition.

Fibroblastic Rheumatism Versus Variant Disease of Multinucleate Cell Angiohistiocytoma.

We report an unusual case of a 49-year-old woman who presented with persistent papulonodules over bilateral fingers and inframammary region in conjunction with features of connective tissue disease including symmetrical polyarthritis and Raynaud phenomenon. Skin biopsy showed an upper-to-mid dermal proliferation of bland spindled cells with thickened collagen bundles and occasional multinucleated giant cells. Dermal blood vessels were only marginally increased. On immunohistochemistry, both the spindled cells and multinucleated giant cells stained negatively for smooth muscle actin. Some of the spindled cells stained positively with CD68 and CD163, whereas the multinucleated giant cells stained negatively for both stains. Elastic fibers were absent on elastic Van Gieson. The clinical and histopathologic features raise a diagnostic dilemma between fibroblastic rheumatism and multinucleate cell angiohistiocytoma. The patient responded well to cyclosporine and methotrexate therapy, with gradual improvement of the finger nodules.

Cutaneous plasmacytosis and multinucleate cell angiohistiocytoma-like lesion in a patient with hepatitis B: A fortuitous triad?

A 28-year-old woman of Chinese descent, with congenital chronic hepatitis B presented with a 7-year history of erythematous-brown papules and plaques on her groins, axillae, and forehead. A first skin biopsy showed findings consistent with two concomitant, yet highly uncommon cutaneous diseases. The presence of lymphoid nodules with germinal centers and clustered polyclonal plasma cells was consistent with cutaneous plasmocytosis. Second, a diffuse proliferation of non-atypical small vessels (CD31+, CD34+, and HHV8-) in a hypercellular stroma peppered with angulated giant cells (CD163+, CD68-) was suggestive of multinucleate cell angiohistiocytoma (MCAH). Interestingly, the second biopsy of a different plaque on the forehead showed only plasmacytosis and the clinical appearance of both plaques and papules alluded to the distinct presence of both concurrent entities. We speculate the immune modulating effects of chronic hepatitis B may have led to a polyclonal plasmacytic proliferation within the dermis. Furthermore, MCAH has been reported in conjunction with other inflammatory skin diseases such as hidradenitis suppurativa and as such we propose that the MCAH lesion in our case may have arisen as a secondary, reactive process to the cutaneous plasmacytosis.

Multinucleate cell angiohistiocytoma: Case report and literature review.

Multinucleate cell angiohistiocytoma is a rare, vascular, fibrohistiocytic proliferation that has a benign but progressive course. The clinical presentation is that of grouped red-purple papules and nodules characteristically located on the lower extremities in women. The histopathology shows a proliferation of narrow vessels within thickened collagen bundles associated with multinucleate giant cells. These lesions are probably reactive in nature, and several mechanisms of pathogenesis, including hormonal, have been proposed. Different modalities, including intense pulsed light and pulsed-dye laser, have been used for treatment of these lesions. We report a case of a 74-year-old Caucasian woman with long-standing multinucleate angiohistiocytoma on her bilateral thighs that eluded diagnosis for several years. Upon biopsy and histopathological analysis, the diagnosis was made. Treatment options were entertained, although ultimately not pursued by the patient. We report this case to increase clinical awareness of this rare disease and to contribute to the ongoing literature aimed to further characterize this condition.

An unusual case of interstitial lung disease in a patient with cardiopulmonary syndrome as the initial presentation of Erdheim-Chester disease.

Erdheim-Chester disease (ECD) is a very rare disorder with only approximately 600 cases reported in the literature. ECD has been recently reclassified as a histiocytic dendritic cell neoplasm. The clinical spectrum ranges from asymptomatic tissue accumulation of histiocytes to invasive tissue infiltration, which can cause fulminant multisystem failure. It typically presents with bone pain and constitutional symptoms. Extraosseous manifestations are not uncommon. ECD-associated interstitial lung disease has been described in 20%-35% of patients. Diagnosis is primarily by tissue biopsy and immunohistochemistry showing xanthogranulomas composed of foamy histiocytes that stain positive for CD68, CD14 and CD163 and negative for CD1á and langerin. We report a case of ECD in a young man with cardiopulmonary involvement who presented with haemoptysis and dyspnoea.

Xanthomatous Posttraumatic Fibro-Osseous Lesion of the Rib: A Rare and Underrecognized Entity. Case Report and Literature Review.

Posttraumatic fibro-osseous lesion (PTFOL) is a rare lesion that typically affects the ribs and is probably a posttraumatic reactive process. Because PTFOL is often misdiagnosed as fibrous dysplasia, osteoid osteoma, benign fibrous histiocytoma or rib metastases, chest wall resection, leading to a significant morbidity, is the main treatment modality. We report the case of a 30-year-old male patient with no history of previous trauma presenting with chest pain. Computed tomography scan showed an eighth left rib well-defined ovoid and hypodense lesion with circumferential sclerotic margin and no cortical breakthrough. Posterolateral thoracotomy was performed and a histological diagnosis of xanthomatous posttraumatic fibro-osseous lesion of the rib was made. PTFOL is a benign lesion that should be recognized to avoid unnecessary surgical treatment and complications. We provide a summary of clinical, histopathological, and radiological aspects of PTFOL and discuss differential diagnoses.

Treatment of tumor in lymph nodes using near-infrared laser light-activated thermosensitive liposome-encapsulated doxorubicin and gold nanorods.

Tumor metastasis to lymph nodes is an important contributory factor for cancer-related deaths despite recent developments in cancer therapy. In this study, we demonstrate that tumor in the proper axillary lymph node (PALN) of the mouse can be treated by the application of external laser light to trigger the unloading of doxorubicin (DOX) encapsulated in thermosensitive liposomes (TSLs) administered together with gold nanorods (GNRs). GNRs + DOX-TSLs were injected into a mouse lymph node containing cancer cells (malignant fibrous histiocytoma-like cells) and intranodal DOX release was activated using near-infrared (NIR) laser irradiation. The temperature changes arising from the laser-irradiated GNRs triggered the release of DOX from the TSLs. A greater degree of inhibition of tumor growth was found in the co-therapy group compared to the other groups. The treatment effect was achieved by a combination of chemotherapy and NIR-activated hyperthermia. In vivo bioluminescence imaging and histological analysis confirmed tumor necrosis in response to combined treatment. This work presents a theranostic approach with excellent treatment results that has the potential to be developed into an alternative to surgery for the treatment of breast cancer metastasis.

Antitumor effect of YM155, a novel small-molecule survivin suppressant, via mitochondrial apoptosis in human MFH/UPS.

Survivin is a member of the inhibitor of apoptosis family, which is known to inhibit mitochondrial apoptosis. Survivin is highly expressed in cancers and plays an important role in cancer cell survival, and increased survivin expression is an unfavorable prognostic marker in cancer patients. YM155, a novel small-molecule survivin suppressant, selectively suppresses survivin expression, resulting in the induction of apoptosis in various malignancies. However, the roles of survivin in human malignant fibrous histiocytoma/undifferentiated pleomorphic sarcoma (MFH/UPS) have not been studied. In the present study, we examined survivin expression in human musculoskeletal tumor tissues, and the effect of survivin inhibition by siRNA or YM155 on apoptotic activity in human MFH/UPS cell lines. In tumor tissues, mRNA expression of survivin was significantly higher in MFH/UPS samples than in benign schwannomas. Moreover, in vitro studies revealed that both survivin siRNA and YM155 suppressed survivin expression and inhibited MFH/UPS cell proliferation in a dose- and a time-dependent manner. Further, the numbers of apoptotic cells significantly increased with YM155 treatment. in vivo, tumor volume in YM155-treated groups was significantly reduced without significant bodyweight loss. Increased apoptotic activity along with decreased survivin expression was also observed in YM155-treated tumors. The findings in this study strongly suggest that survivin suppressants, including YM155, contribute to the suppression of human MFH/UPS cell growth via promoting mitochondrial apoptosis, and that survivin may be a potent therapeutic target for the novel treatment of human MFH/UPS.

Scrotal tumors in dogs: a retrospective study of 676 cases (1986-2010).

The objective of this study was to determine common tumor types that occur on the canine scrotum in relation to other cutaneous locations and to identify potential risk factors for specific scrotal tumor development. A retrospective study was conducted and the database of pathology reports from the Surgical Pathology Service of the Department of Pathology and Toxicology, School of Veterinary Medicine, University of Pennsylvania from 1986 to 2010 was searched for canine neoplastic scrotal and non-scrotal cutaneous lesions. Neoplastic lesions were evaluated based on diagnosis, breed, age, and number and location of tumors (scrotal versus non-scrotal cutaneous). Mast cell tumor, melanocytoma, malignant melanoma, vascular hamartoma, hemangiosarcoma, hemangioma, and cutaneous histiocytoma were the most common tumor types identified on the canine scrotum. Breed predispositions and mean age at diagnosis were identified for each tumor type and should be considered when planning surgical excision of a canine scrotal tumor.

Tumeurs scrotales chez les chiens : étude rétrospective de 676 cas (1986­2010). Cette étude avait pour objectif de déterminer les types communs de tumeurs qui se produisent sur le scrotum canin par rapport à d'autres endroits cutanés et d'identifier les facteurs de risque potentiels pour le développement de tumeurs scrotales spécifiques. Une étude rétrospective a été réalisée et une recherche a été effectuée dans la base de données des rapports de pathologie du Service de pathologie chirurgicale du Département de pathologie et de toxicologie de l'École de médecine vétérinaire de l'Université de la Pennsylvanie de 1986 à 2010 pour les lésions scrotales néoplasiques et les lésions cutanées non scrotales canines. Les lésions néoplasiques ont été évaluées en fonction du diagnostic, de la race, de l'âge ainsi que du nombre et de l'emplacement des tumeurs (scrotales par opposition à cutanées non scrotales). Les tumeurs à mastocytes, les mélanocytomes, les mélanomes malins, les hamartomes vasculaires, les hémangiosarcomes, les hémangiomes et les histiocytomes cutanés étaient les types les plus communs de tumeurs identifiées sur le scrotum canin. Les prédispositions des races et l'âge moyen lors du diagnostic ont été identifiés pour chaque type de tumeur et devraient être considérés lors de la planification de l'excision chirurgicale d'une tumeur scrotale canine.(Traduit par Isabelle Vallières).

Epithelioid fibrous histiocytoma EMA positivity: a case report.

A case of epithelioid fibrous histiocytoma diagnosed in a 5-year-old female with a skin lesion: morphological description and immunohistochemical investigations performed.

Regression of canine cutaneous histiocytoma is associated with an orchestrated expression of matrix metalloproteinases.

Canine cutaneous histiocytoma (CCH) is a common benign skin tumour originating from epidermal Langerhans cells. These tumours often display spontaneous regression and therefore represent a valuable animal model for investigation of tumour regression. Based on previous studies it was hypothesized that up-regulation of cytokines during CCH regression leads to up-regulation of matrix metalloproteinases (MMPs) favouring infiltration of lymphocytes and enhanced tumour regression. The expression of MMPs and their inhibitors (tissue inhibitors of metalloproteinases, TIMPs) was investigated immunohistochemically in 27 CCHs. The tumours were classified into four groups defined as having no regression (group 1), early regression (group 2), intermediate regression (group 3) or late regression (group 4). The distribution and expression intensity of MMP-1, -2, -3, -7, -9, -13 and -14 and TIMP-1 and -2 were determined in peripheral and central areas of each tumour. Group 3 and 4 CCHs showed up-regulation of expression of MMP-1, -9 and -14 at the periphery. Variable expression of MMP-2 and -3 was observed. Expression of the remaining MMPs and TIMPs showed no group-specific changes. Most MMPs and TIMPs displayed significantly higher expression at the tumour periphery compared with the centre, independently of the stage of regression and indicating more pronounced proteolysis in the peripheral areas. The results are consistent with cytokine-enhanced MMP expression, particularly of MMP-9, leading to enhanced lymphocyte recruitment in combination with elevated cleavage of extracellular matrix and basement membranes.

Generalized eruptive histiocytoma: a rare disease in an elderly patient.

Generalized eruptive histiocytoma is considered an extremely rare subtype of non-Langerhans cells histiocytosis. In the literature, there are few reports of this disease that mainly affects adults. In this report, we present a case of generalized eruptive histiocytoma in an elderly patient who had presented symptoms for over two months. Multiple erythematous papules, asymptomatic and symmetrically distributed were observed on the trunk and limbs. Histological examination showed a dense mononuclear cell dermal infiltrate. In the immunohistochemical analysis, the cells were CD68 positive, but CD1a, S100 and CD34 negative. A diagnosis of generalized eruptive histiocytoma was established. The aim of our paper is to report a case of a very rare disease, whose subtype and affected age group are even more unusual.