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.

Spindle cell variant of epithelioid cell histiocytoma (spindle cell histiocytoma) with ALK gene fusions: Cases series and review of the literature.

BACKGROUND: Epithelioid fibrous histiocytoma (EFH) is an uncommon dermal neoplasm expressing anaplastic lymphoma kinase (ALK) protein. Rarely a histopathological variant of this entity exhibits exclusively spindle cells. We report three cases of EFH that do not completely fulfill phenotypic criteria featuring spindle cell morphology and expressing ALK protein. We also analyze the fusion partner genes rearranged with ALK in these cases. METHODS: ALK expression and rearrangement status were evaluated by immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and next generation sequencing based gene fusion analysis. RESULTS: Three cases, all from females between 25 and 55 years old, have been biopsied from back, left arm, and thumb. All three cases showed tumor with exclusively spindle cell morphology without any epithelioid cells. The tumor cells exhibited strong ALK expression by IHC and FISH study confirmed ALK gene rearrangement in all three cases. DCTN1-ALK fusion was identified in two cases. CONCLUSION: EFH is not always purely epithelioid and its spindled cell variant, spindle cell histiocytoma, should be included in the differential diagnosis of superficial dermal spindled cell neoplasms. ALK immunostain is a useful diagnostic marker for this entity and further studies may be useful to investigate whether DCTN1-ALK fusion mutations are specific to EFH with spindled cell features.

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.

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.

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.

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.

Histiocytic neoplasms in the era of personalized genomic medicine.

PURPOSE OF REVIEW: Since the discovery of B-Raf proto-oncogene (BRAF) V600E mutations in histiocytic neoplasms, diverse kinase alterations have been uncovered in BRAF V600E-wildtype histiocytoses. The purpose of this review is to outline recent molecular advances in histiocytic neoplasms and discuss their impact on the pathogenesis and treatment of these disorders. RECENT FINDINGS: Activating kinase alterations discovered in BRAF V600E-wildtype Langerhans (LCH) and non-Langerhans cell histiocytoses (non-LCH) result in constitutive activation of the mitogen-activated protein kinase and/or phosphoinositide 3-kinases-Akt murine thymoma pathways. These kinase alterations include activating mutations in A-Raf proto-oncogene, mitogen-activated protein kinase kinase 1, neuroblastoma rat sarcoma viral oncogene homolog, Kirsten rat sarcoma viral oncogene homolog, and phosphatidylinositol-4,5-bisphosphate 3 kinase, catalytic subunit α kinases in LCH and non-LCH; BRAF, anaplastic lymphoma receptor tyrosine kinase, and neurotrophic tyrosine kinase, receptor type 1 fusions, as well as the Ets variant 3-nuclear receptor coactivator 2 fusion in non-LCH; and mutations in the mitogen-activated protein kinase kinase kinase 1 and Harvey rat sarcoma viral oncogene homolog kinases in LCH and histiocytic sarcoma, respectively. These discoveries have refined the understanding of the histiocytoses as clonal, myeloid neoplasms driven by constitutive mitogen-activated protein kinase signaling and identified molecular therapeutic targets with promising clinical responses to rapidly accelerated fibrosarcoma and mitogen-activated protein kinase kinase inhibition. SUMMARY: Genomic analyses over the last 6 years have identified targetable kinase alterations in BRAF V600E-wildtype histiocytic neoplasms. However, despite this progress, the molecular pathogenesis and therapeutic responsiveness of non-BRAF V600E kinase alterations are still poorly defined in these disorders.

Hot spleen: hypervascular lesions of the spleen.

The differential diagnosis of splenic masses is broad and often hinges on the enhancement characteristics of the lesions. Most radiologists are familiar with the differential diagnosis of hypovascular lesions such as fungal infections, sarcoidosis/granulomatous disease, infarctions, and cysts. However, to our knowledge, there is no review article that presents the specific multimodality imaging features of vascular splenic lesions as a group. Vascular splenic lesions may be considered those that enhance more or similarly to the background splenic parenchyma. In this review, we illustrate the spectrum of imaging features of both benign and malignant vascular splenic lesions. The benign lesions include hemangiomas, hamartomas, and sclerosing angiomatoid nodular transformation of the spleen. The malignant lesions are divided into primary and metastatic lesions, ranging from lymphoma, angiosarcoma to pleomorphic sarcoma. While lymphoma and metastases may commonly present as hypoenhancing lesions relative to the background parenchyma, we are addressing them here as their appearance can be varied and hence deserve consideration. Littoral Cell angiomas are discussed separately, as they were originally considered benign, but recent studies have shown that they can have malignant potential.

Inflammatory Myofibroblastic Tumor of the Oral Cavity. A Great Mimicker.

Inflammatory myofibroblastic tumor (IMT) is a seldom-described tumor of indefinite etiology and pathogenesis. It occurs primarily in the lungs, but has occurred in other extra-pulmonary sites. Histologically, these lesions appear as an inflammatory infiltrate within a variably myofibrotic background. Current evidence shows that inflammatory myofibroblastic tumors are neoplastic processes resulting from chromosomal translocations that frequently cause an overexpression of ALK kinase, often assessed using immunohistochemical studies. Currently, the biological behavior of oral IMT is still uncertain. This article illustrates the clinical, histological and operative features of a case of IMT of the oral cavity.

Oral contraceptive use, parity, and constitutional characteristics in soft tissue sarcoma: a Swedish population-based case-control study 1988-2009.

PURPOSE: The study was designed to investigate the influence of surrogate factors associated with sex (SH) and growth hormones (GH) on the risk of developing soft tissue sarcomas (STS). BACKGROUND AND METHODS: The etiology of soft tissue sarcoma is largely unknown. We have studied the effect of hormone related factors on STS in the Swedish population between 1988 and 2009 using a population-based matched case-control design. RESULTS: Our study is the largest on this topic to date, including 634 cases in a primary matched analysis and 855 cases in an unmatched sensitivity analysis. We identified protective effects connected to constitutional characteristics, hormonal and reproductive factors. Being shorter than your peers at age 11 was associated with an odds ratio (OR) of 0.51 (0.36-0.74). Having used oral contraceptives (OC), OR 0.75 (0.49-1.15), and high parity, OR 0.16 (0.04-0.63), comparing three or more children to two or less, also appeared to reduce the risk of STS. The risk was further reduced with the duration of OC use (p = 0.01), comparing use for 11 years or more to use for 3 years or less yielded an OR of 0.10 (0.02-0.41). No effect was observed for ever having had perimenopausal hormone therapy OR 1.02 (0.70-1.47). The effect of BMI varied significantly with subtype (p = 0.03) and tumor location (p < 0.001). CONCLUSIONS: We observed surrogates of SH, GH, and insulin-like growth factor 1 to be associated with STS development. These findings are important as they may connect STSs to the group of hormone-dependent tumors, potentially revealing common treatment and prevention targets.

Understanding semantic mapping evolution by observing changes in biomedical ontologies.

Knowledge Organization Systems (KOSs) are extensively used in the biomedical domain to support information sharing between software applications. KOSs are proposed covering different, but overlapping subjects, and mappings indicate the semantic relation between concepts from two KOSs. Over time, KOSs change as do the mappings between them. This can result from a new discovery or a revision of existing knowledge which includes corrections of concepts or mappings. Indeed, changes affecting KOS entities may force the underline mappings to be updated in order to ensure their reliability over time. To tackle this open research problem, we study how mappings are affected by KOS evolution. This article presents a detailed descriptive analysis of the impact that changes in KOS have on mappings. As a case study, we use the official mappings established between SNOMED CT and ICD-9-CM from 2009 to 2011. Results highlight factors according to which KOS changes in varying degrees influence the evolution of mappings.

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).

Epidemiology of canine cutaneous round cell tumours on the canary archipelago in Spain.

In this study we undertook a comprehensive analysis of a Pet Tumour Registry of the Canary Archipelago (PTR-CA) in Spain to investigate the epidemiology of canine cutaneous round cell tumours. From a database of 2526 tumours collected from 2003 to 2020, we conducted a longitudinal analysis of the main trends in diagnosis, age, multiplicity and anatomical distribution as well as a case-control study comparing these cases with the contemporaneous canine population of the Canary Archipelago to analyse breed distribution. In line with former studies, we found histiocytomas mostly affect young dogs (2, IQR 1-5) and mast cell tumours affect middle-to-old dogs (8, IQR 6-10) with grade 1 affecting at younger ages (6.5, IQR 6-8) than both grade 2 (8, IQR 6-10 years) and grade 3 (9, IQR 7-11). Histiocytomas and plasmacytomas showed a similar anatomical distribution appearing mainly on the face, head and neck regions while mast cell tumours occur mainly on limbs and trunk. Higher risk for mast cell tumours and histiocytomas were found for Bulldog-related breeds such as Boxer (ORMCT = 23.61, CI95%: 19.12-29.15, ORHCT = 10.17, CI95%: 6.60-15.67), Boston Terrier (ORMCT 19.47, CI95%: 7.73-49.05, ORHCT 32.61, CI95%: 11.81-90.07) and Pug (ORMCT 8.10, CI95%: 5.92-11.07, ORHCT 7.87, CI95%: 4.66-13.28) while Chihuahua dogs showed significantly less risk (ORMCT 0.18, CI95%: 0.09-0.33, ORHCT 0.41, CI95%: 0.21-0.78). Notably, the Canarian Mastiff, a local breed, had a low risk of suffering from a mast cell tumour which raises the question of whether this relates to a genetic peculiarity of this breed or some husbandry and environmental factor.

Expanding Our Knowledge of Molecular Pathogenesis in Histiocytoses: Solitary Soft Tissue Histiocytomas in Children With a Novel CLTC::SYK Fusion.

The histiocytoses comprise a histopathologically and clinically diverse group of disorders bearing recurrent genomic alterations, commonly involving the BRAF gene and mitogen-activated protein kinase pathway. In the current study, a novel CLTC :: SYK fusion in 3 cases of a histopathologically distinct histiocytic neoplasm arising as solitary soft tissue lesions in children identified by next-generation sequencing and fluorescence in situ hybridization is described. Morphologically, all 3 neoplasms were composed of sheets of cells with round-oval nuclei and vacuolated eosinophilic cytoplasm but, in contrast to classic juvenile xanthogranuloma (JXG), Touton giant cells were absent. A separate cohort of classic JXG cases subsequently profiled by fluorescence in situ hybridization were negative for the presence of a CLTC::SYK fusion suggesting that CLTC::SYK fusion-positive histiocytoma is genetically and histologically distinct from JXG. We postulate that the CLTC::SYK fusion leads to aberrant activation of the SYK kinase, which is involved in variable pathways, including mitogen-activated protein kinase. The identification of a novel CLTC::SYK fusion may pave the way for the development of targeted therapeutic options for aggressive disease.

Granular cell variant of epithelioid cell histiocytoma.

Classic granular cell tumors (GCTs) stain strongly and uniformly positive for S100 protein and are believed to show Schwann cell derivation. Polypoid cutaneous tumors composed of cells with large nuclei and abundant granular cytoplasm that do not stain for S100 protein or show apparent Schwannian differentiation have been reported by several groups under names including "primitive polypoid granular cell tumors," "dermal nonneural granular cell tumor," and "primitive nonneural granular cell tumors of skin." We report a polypoid tumor composed of S100-negative epithelioid cells with abundant eosinophilic granular cytoplasm that meets diagnostic criteria for (primitive polypoid dermal) nonneural GCT but also meets criteria for a granular cell variant of epithelioid cell histiocytoma. We have identified a single previous report of a similar lesion. We report the immunohistochemical characteristics of these lesions and address how they are best classified.

A case of congenital solitary Langerhans cell histiocytoma.

A newborn baby boy was referred to the Paediatric Dermatology Unit with a solitary asymptomatic nodule overlying his right nasolabial fold. Complete physical examination, full blood count, serum chemistry, liver function tests and baseline imaging were unremarkable. Histopathological examination showed an atypical dermal infiltrate of mononuclear cells that stained positive with CD1a and S100. A diagnosis of congenital solitary Langerhans cell histiocytoma was made. The lesion completely resolved by 4 months of age. The baby is now 15 months old and repeat systemic evaluation has remained normal.