Extracutaneous Sites Research Articles

Juvenile Xanthogranuloma of the Cauda Equina

Juvenile xanthogranuloma is a form of histiocytic proliferative disorder that usually affects the skin and tends to occur during infancy. On rare occasions, it has been reported at extracutaneous sites and in other age groups. Isolated juvenile xanthogranuloma of the nervous system is extremely rare, especially in the cauda equina. A case of juvenile xanthogranuloma of the cauda equina in a 14-year-old boy is reported, and the literature is reviewed.

Intravascular Capillary Hemangioma of the Skin

Capillary hemangiomas are very common benign vascular neoplasms which frequently occur in the skin and intraoral mucous membranes. The intravascular variant of this lesion, however, is distinctly uncommon and has been reported rarely in the English literature. Those reported cases describe this tumor as arising in veins in cutaneous and extracutaneous sites. Here we report two cases of intravascular capillary hemangioma arising in the skin.

The Impact of Therapeutic Management and Prognostic Factors on the Outcome of Primary Cutaneous B-Cell Lymphomas (PCBCL) (IELSG 11 Study)

Primary cutaneous B-cell lymphomas (PCBCL) are a distinct group of primary cutaneous lymphomas with few and controversial reports on their treatment and prognostic factors. The aim of this retrospective study of a large international series of PCBCL patients was to analyze the patient and lymphoma characteristics as well as treatment-related variables associated with clinical outcome. From 1980 to 2006, 507 patients were referred to 19 cancer centers of 6 countries all over the world. The median age was 55 years (range,16–92 years) and the M/F ratio was 1.4. According to the WHO-EORTC classification indolent lymphomas included 341 FCL and 122 MZL, while aggressive NHL were represented by DLBCL, leg type (n=44). Sixty patients (12%) had stage II. The majority of cases was diagnosed in trunk/arms (52%), while in 29% in head/neck and in 13% in the legs; 7% of patients had a generalized disease (>1 site). The maximal lesion diameter was >4 cm in 21% of cases and ≥2 lesions were recorded in 39%. The prevailing type of lesions were nodules (74%), while only a minority of patients (6%) were affected by tumors. Few patients had B symptoms (5%), poor ECOG-PS (9%) or elevated LDH (7%). Two hundred eighty-four out of 446 patients (64%) were treated only with surgery (n=86) or chemotherapy (n=95), mostly consisting of a short course of anthracyclin containing regimens, or radiotherapy (30–50 Gy) (n=103). One hundred sixty two cases (36%) received combined therapy, mostly including surgery or chemotherapy, followed by radiotherapy. A small subgroup of 35 patients were given rituximab alone (n=19) or in combination with other treatments. The remaining 26 patients did not receive any therapy. The response rate of 446 patients was the following: 402 achieved CR (86%), 38 PR and 6 were in SD. Neither histology nor treatment significantly influenced CR rate. Among 402 responders, 128 (32%) eventually relapsed, 86% in the skin, 10% in extracutaneous sites and 4% in both. The relapse rate varied according to histology, ranging from 52% in DLBCL leg-type to 29% in MZL and 28% in FL. Moreover, combined treatments significantly reduced relapse rate (24% vs. 37%; p=0.008). The achievement and maintenance of CR significantly influenced the long-term disease specific survival (at 20 year 99 % vs. 45%; p=0.0001). The CR rate of subgroup of 35 patients treated with rituximab, was 74%, while the relapse rate was 35%. These results were not influenced by the addition of other therapies to rituximab. After a median follow-up of 53 months (range, 2–333 months), 5 and 10-year estimate of OS, disease-specific survival, PFS and DFS were 91%, 92%, 61%, 65% and 82%, 88%, 49% and 56%, respectively. Cox multivariate analysis, stratified for age with a stepwise selection of the significant variables, identified DLBCL, leg-type histology, elevated LDH, type of lesion (nodules and tumors), B symptoms and female gender, as significant predictors of a poor OS. In conclusion this retrospective analysis confirms, on a large series of cases, that patients with PCBCL belong to different risk categories requiring a tailored treatment approach. These data can be usefully taken into account for an adequate management strategy of PCBCL patients.

Coincidence of cutaneous follicle center lymphoma and diffuse large B‐cell lymphoma

Primary cutaneous follicle center lymphoma (PCFCL) is a neoplasm with differentiation of centrocytes and centroblasts presenting in the skin. At the time of initial manifestation, extracutaneous involvement is absent. PCFCL is considered as an indolent variant of primary cutaneous B-cell lymphomas since dissemination to extracutaneous sites is rare and the prognosis is favorable. Here we describe a 30-year-old man who was diagnosed with a cutaneous FCL and did not show extracutaneous affection at the time of occurrence. Six months later, however, he developed a diffuse large B-cell non-Hodgkin lymphoma localized in several lymph nodes of the neck that most likely reflects the occurrence of a second primary tumor in the same patient.

Lymphome cutané de la zone marginale : étude histologique et immunophénotypique de 49 cas

No histological or clinical criteria allow distinction between primary cutaneous marginal zone B-cell lymphoma (MZL) and secondary cutaneous forms of systemic marginal zone B-cell lymphoma. Consequently, staging alone can indicate the origin of lymphoma. Lymphoma is considered as primary cutaneous only if no other extracutaneous sites are found. We studied the histological appearance of 49 cutaneous lymphomas in order to find distinctive criteria indicative of an extracutaneous origin. This was a retrospective descriptive study of histological appearance for 49 patients with cutaneous marginal lymphoma: 29 cases of the primary form and 20 cases with extracutaneous involvement. Comparison of histological criteria did not reveal any differences between the primary cutaneous form and others forms. No prognostic criteria for relapse were found. A cutaneous tropism of primary MZL suggested the hypothesis of specific cutaneous receptors on B-cells that could have led to different histological appearances depending on the origin of the lymphoma. However, our study did not confirm this hypothesis.

Lymphoepithelioma-like carcinoma of the skin: New case of an exceedingly rare primary skin tumor

Lymphoepithelioma-like carcinoma of the skin (LE-lCS) is a very rare, primary skin neoplasm of uncertain origin. The tumor reveals striking morphological similarity to undifferentiated nasopharyngeal carcinoma (lymphoepithelioma). However, the primary skin tumors have never been associated with Epstein-Barr virus (EBV), in contrast to those at some extracutaneous sites. Since the first description by Swanson et al. in 1988, only 46 cases have been documented over the last 20 years. This case report presents an 89-year-old woman with a 0.5 cm plaque-like, discolored lesion on her left cheek of one-month duration. The patient underwent surgical excision and is disease free one year later. The histopathological, immunohistochemical and EBV in situ hybridization features are described. The clinical and pathological differential diagnosis is discussed. This case supports the contention that LE-lCS is not associated with EBV.

Differential Expression of TRAF1 Aids in the Distinction of Cutaneous CD30-Positive Lymphoproliferations

Lymphomatoid papulosis (LyP), primary cutaneous anaplastic large T-cell lymphoma (cALCL), and cutaneous infiltrates of systemic anaplastic large cell lymphoma (sALCL) are CD30-positive lymphoproliferative disorders of the skin that overlap clinically, histopathologically, immunophenotypically, and genetically but differ considerably in their prognosis. In particular, lesions of LyP regress spontaneously, whereas those of cALCL and sALCL persist and may progress and spread to extracutaneous sites. In contrast to patients with cALCL, LyP patients do not benefit from an aggressive radio- and/or chemotherapeutic approach. We generated a novel tumor necrosis factor receptor (TNFR)-associated factor 1 (TRAF1) antibody that recognizes a formalin-resistant epitope (Ber-TRAF1A) and investigated the expression of TRAF1, an intracellular component of TNFR signaling, in LyP and ALCL. We could show a strong TRAF1 expression in the tumor cells of most LyP cases (42/49, 84%). In contrast, tumor cells of primary and secondary cALCL revealed TRAF1 expression in only a few cases (3/41, 7%) as shown for sALCL without skin manifestation. The data indicate that TRAF1 expression reliably distinguishes LyP from primary or secondary cALCL. This might be of crucial diagnostic importance and has a strong impact on the treatment decision for patients with cALCL and LyP.

Necrobiotic Xanthogranuloma

Necrobiotic xanthogranuloma (NXG) is an uncommon granulomatous disease involving the skin and extracutaneous tissues. In its typical clinical presentation, it consists of multiple indurate yellow-brownish plaques or nodules, usually located on the periorbital area. The lesions often are bilateral and symmetric and frequently show tendency to atrophy and ulceration. Most cases are asymptomatic, and oral mucosal erosions are sometimes present. Ophthalmologic complications are observed in many patients, and NXG may involve other extracutaneous sites. Paraproteinemia is closely associated with NXG, demonstrating a monoclonal gammapathy, and other hematologic or lymphoproliferative disorders also may appear in association with NXG. Large areas of degenerated collagen alternating with granulomatous inflammation, multinucleate giant cells, cholesterol clefts, and lymphoid follicles are the most outstanding histopathologic characteristics of NXG. The prognosis for NXG is good, but no curative treatment is available. Chemotherapy with alkylating agents is the most frequently administered treatment, but oral and intralesional corticosteroids, interferon alpha, plasmapheresis, surgical excision, and radiation therapy also have been used for treatment of this disorder, with variable results.

Systemic Juvenile Xanthogranulomatosis Imitating a Malignant Abdominal Wall Tumor With Lung Metastases

Juvenile xanthogranulomatosis (JXG) is a rare benign condition, which usually presents with characteristic skin lesions and can be diagnosed clinically. However, systemic JXG may involve a wide range of extracutaneous sites and may pose a diagnostic dilemma for the clinician, radiologist, and pathologist. In particular it may simulate malignancy. Here, we report a case of systemic JXG within the abdominal wall musculature and lungs, which imitated a sarcoma with pulmonary metastases on computerized tomography. To the best of our knowledge, this is the first such reported case. In particular, systemic disease presenting without skin lesions is unusual.

Mycobacterium haemophilum osteomyelitis: case report and review of the literature

BackgroundMycobacterium haemophilum is a slow-growing, fastidious, iron-requiring microorganism that, relative to other non-tuberculous mycobacterial species, has rarely been documented as a cause of human infection. This microorganism appears to be acquired via environmental exposure although its natural habitat and mode of acquisition are unknown. It has primarily been implicated as a cause of ulcerating cutaneous or subcutaneous nodular skin lesions, particularly in immunocompromised patients, although infections at extracutaneous sites have also been described. Osteomyelitis, while rarely documented, appears to be an important complication of infection with M. haemophilum in these patients.Case presentationWe describe a unique case of culture-confirmed M. haemophilum osteomyelitis in an adult woman with polycythemia vera and review the world literature on bone infections due to this organism.ConclusionMycobacterium haemophilum is an important but infrequently encountered cause of osteomyelitis in immunocompromised patients, often requiring months to years of medical therapy, with or without surgery, to effect a clinical cure.

Melanoma risk in congenital melanocytic naevi: a systematic review

The risk of malignant melanoma in congenital melanocytic naevi (CMN) is a matter of controversial and ongoing debate. The purpose of this systematic review is to provide a careful and detailed summary of the published data, including several recently published studies. Articles on CMN (n=1424) were retrieved from Medline, 1966-October 2005. Case reports and studies lacking relevant clinical information were excluded. Only systematic collections of cases were taken into consideration. Series with fewer than 20 patients or studies with a mean follow-up of <3 years were regarded as epidemiologically less significant. Fourteen articles were finally chosen for further analysis. The studies varied significantly with respect to study design (source of cases; retrospective vs. prospective analysis), age of patients, follow-up time, and naevus characteristics. The frequency of melanomas ranged between 0.05% and 10.7% and was significantly higher in smaller studies (P<0.0001). In a total of 6571 patients with CMN who were followed for a mean of 3.4-23.7 years, 46 patients (0.7%) developed 49 melanomas. The mean age at diagnosis of melanoma was 15.5 years (median 7). By comparison with age-adjusted data from the Surveillance, Epidemiology and End Results database, we calculated that patients with CMN carry an approximately 465-fold increased relative risk of developing melanoma during childhood and adolescence. Primary melanomas arose inside the naevi in 33 of 49 cases (67%). In seven cases (14%), metastatic melanoma with unknown primary was encountered; in four cases (8%) the melanoma developed at an extracutaneous site. The risk of developing melanoma and the rate of fatal courses were by far highest in CMN>or=40 cm in diameter. The overall risk of melanoma of 0.7% in all 14 studies was lower than expected. The higher incidence of melanomas in smaller studies indicates selection bias. The melanoma risk strongly depends on the size of CMN and is highest in those naevi traditionally designated as garment naevi. The median age of 7 years at diagnosis of melanoma points to a risk maximum in childhood and adolescence. Future studies on CMN should report: (i) diameter, percentage of body surface, and localization of the CMN; (ii) percentage of naevus area removed by excision or subject to dermabrasion or other superficial treatments; (iii) mean and median age at entry into the study; (iv) mean and median follow-up time; (v) details on each melanoma case; (vi) standardized morbidity ratio of melanoma; and (vii) percentage of neurocutaneous melanosis.

Lymphoepithelioma-Like Carcinoma of the Skin in a Tunisian Patient

Lymphoepithelioma-like carcinoma of the skin (LELCs) is a rare cutaneous neoplasm with histologic features resembling lymphoepitheliomatous tumors of the nasopharynx. The association of lymphoepitheliomas with Epstein-Barr Virus (EBV) at some extracutaneous sites is well documented. In contrast, the presence of EBV in LELCs has never been shown in either Caucasians or Asian patients. We present the first case of LELCs in a Tunisian patient, a 78-year-old woman who presented with a nodule of the right cheek of 2 months' duration. The patient underwent surgical excision and there was no evidence of local recurrence 6 months later. Histologically, the entire dermis was occupied by lobules composed of atypical epithelial cells surrounded by a dense lymphoplasmacytic infiltrate. Immunohistochemical examination showed that the epithelial tumor cells were positive for cytokeratin and epithelial membrane antigen. In situ hybridization investigations for the presence of EBV-encoded RNA showed negative results. Our findings suggest that LELCs is not related to EBV among North African patients.

Diagnosis of lyme borreliosis.

A large amount of knowledge has been acquired since the original descriptions of Lyme borreliosis (LB) and of its causative agent, Borrelia burgdorferi sensu stricto. The complexity of the organism and the variations in the clinical manifestations of LB caused by the different B. burgdorferi sensu lato species were not then anticipated. Considerable improvement has been achieved in detection of B. burgdorferi sensu lato by culture, particularly of blood specimens during early stages of disease. Culturing plasma and increasing the volume of material cultured have accomplished this. Further improvements might be obtained if molecular methods are used for detection of growth in culture and if culture methods are automated. Unfortunately, culture is insensitive in extracutaneous manifestations of LB. PCR and culture have high sensitivity on skin samples of patients with EM whose diagnosis is based mostly on clinical recognition of the lesion. PCR on material obtained from extracutaneous sites is in general of low sensitivity, with the exception of synovial fluid. PCR on synovial fluid has shown a sensitivity of up to >90% (when using four different primer sets) in patients with untreated or partially treated Lyme arthritis, making it a helpful confirmatory test in these patients. Currently, the best use of PCR is for confirmation of the clinical diagnosis of suspected Lyme arthritis in patients who are IgG immunoblot positive. PCR should not be used as the sole laboratory modality to support a clinical diagnosis of extracutaneous LB. PCR positivity in seronegative patients suspected of having late manifestations of LB most likely represents a false-positive result. Because of difficulties in direct methods of detection, laboratory tests currently in use are mainly those detecting antibodies to B. burgdorferi sensu lato. Tests used to detect antibodies to B. burgdorferi sensu lato have evolved from the initial formats as more knowledge on the immunodominant antigens has been collected. The recommendation for two-tier testing was an attempt to standardize testing and improve specificity in the United States. First-tier assays using whole-cell sonicates of B. burgdorferi sensu lato need to be standardized in terms of antigen composition and detection threshold of specific immunoglobulin classes. The search for improved serologic tests has stimulated the development of recombinant protein antigens and the synthesis of specific peptides from immunodominant antigens. The use of these materials alone or in combination as the source of antigen in a single-tier immunoassay may someday replace the currently recommended two-tier testing strategy. Evaluation of these assays is currently being done, and there is evidence that certain of these antigens may be broadly cross-reactive with the B. burgdorferi sensu lato species causing LB in Europe.

Primary cutaneous follicular center cell lymphoma of the nose with maxillary sinus involvement in a pediatric patient

We report a primary cutaneous follicular center cell lymphoma (PCFCCL) that arose on the nose and the left naso-labial fold, spread to the left cheek, the left maxillary sinus, and the soft palate in a 16-year-old boy. Polychemotherapy was performed and the patient is disease-free after 41 months. This case is unusual because PCFCCL rarely arises on the nose, only occasionally disseminates to extracutaneous sites, and, to our knowledge, has never been described in pediatric patients.

Primary Mucinous Carcinoma of the Scalp-A Case Report

Primary mucinous carcinoma of the skin is a rare tumor with only cases reported in the literature since the first description of a case by Lennox et al. in 1952. This tumor is a histologic subtype of sweat gland carcinoma. Because of the histopathologic appearance, primary mucinous carcinoma of skin can be mistaken for metastasis from extracutaneous sites. Most cases occur mainly between the fifth and the seventh decade of life. They are growing slowly with a propensity for local recurrence and metastasis. This tumor has not been widely reported in the plastic surgery literature. We describe a 59-year-old woman with a tumor on the right scalp. This lesion enlarged progressively and showed a reddish, elevated, dome-shaped surface. Excisional biopsy of the tumor revealed mucinous carcinoma. Further treatment involved wide local excision and reconstruction. In attempt to improve the recognition of this clinical entity, we discuss the histopathology, clinical course, surgical management and prognosis. Mucinous carcinoma can occur in noncutaneous visceral sites and metastasize to the skin. Systemic investigation were undertaken to exclude the possibility of metastatic mucinous carcinoma.

Intramuscular Juvenile Xanthogranuloma in an Adult

Abstract Juvenile xanthogranuloma (JXG) is a self-limited cutaneous lesion that most often occurs in infancy. Approximately 10% to 30% of JXGs occur in adult patients, where most cases present as cutaneous papulonodular lesions, with only rare cases involving extracutaneous sites. Intramuscular JXG is extremely rare and has received little attention. On review of the literature, all of the 6 previously reported intramuscular JXGs were noted in the pediatric population. The authors hereby describe a case of adult intramuscular JXG that occurred in a woman who initially had a dermal JXG in the nasal skin at the age of 48 years and then developed a slow-growing painless intramuscular JXG in the right forearm 4 years later. Both the dermal and intramuscular lesions revealed similar histologic features and consisted of diffuse infiltrates of histiocytes with eosinophilic and foamy cytoplasm, lymphocytes, eosinophils, and Touton giant cells in varying proportions. However, central fibrosis and a focal storiform arrangement of spindled fibroblast-like cells in the intramuscular lesion resulted in a histologic pattern reminiscent of a fibrous histiocytoma. Immunohistochemically, the intramuscular JXG was positive for CD68, factor XIIIa, CD31, and vimentin. This case underscores the fact that intramuscular JXG can also involve adult patients and its morphologic variation is more likely to be time dependent rather than site specific or age related.

Mucoepidermoid Carcinoma of the Skin: A Distinct Entity From Adenosquamous Carcinoma

Mucoepidermoid carcinoma (MEC) of the skin is an exceedingly rare but distinctive neoplasm with respect to its histopathologic features. It is similar if not identical in most respects to MEC of the salivary gland, a neoplasm whose prognosis is correlated with the pathologic grade. We report a case of MEC of the skin in a 79-year-old white woman who presented with an axillary mass. Beneath an unremarkable epidermis, a circumscribed, cystic neoplasm, unattached to the surface, was characterized by the presence of vague lobules of low-grade-appearing squamous cells accompanied by mucigenic and clear cells. A mucin stain highlighted the mucigenic cells and immunohistochemistry revealed pan-cytokeratin, cytokeratin 7, polyclonal carcinoembryonic antigen, and epithelial membrane antigen positivity. The cytokeratin 20 and gross cystic disease fluid protein were nonreactive. Inconsistency was encountered in the literature where some confusion existed as to whether MEC is synonymous with adenosquamous carcinoma of the skin. Elsewhere in the body, the latter tumor type is a squamous and gland-forming neoplasm with intermediate- to high-grade features rather than a tumor with mucigenic cells intermingled among intermediate and squamous cells. As in the case of MEC and adenosquamous carcinoma elsewhere in extracutaneous sites, we would propose that a pathologic distinction should be made in the skin for the sake of consistency and for prognostic purposes. Additionally, the immunophenotype of our case is similar to at least two other cases of cutaneous MEC, as well as MEC of the salivary gland, to support the hypothesis that this neoplasm is adnexal rather than epidermal in origin.

Cutaneous and Systemic Plasmacytosis

Background: Plasmacytosis is a rare entity, which may manifest with cutaneous patches and plaques and may subsequently progress to involve extracutaneous sites. First described in Japan by Kimura K et al in 1983, most cases have been reported in patients of Asian descent. Observation: We report a case of plasmacytosis in a 52‐year‐old Hispanic woman, who presented ten years ago with cutaneous infiltrates of plasma cells and polyclonal hypergammaglobulinemia. Numerous (immunohistochemical, molecular, serologic) studies failed to demonstrate a clonal lymphoplasmacellular neoplasm, collagen vascular disease or chronic infection. Her course has been slowly progressive with new plaques developing on the integument. Plasma cells have since infiltrated gastric and esophageal mucosa, the left temporal artery and lymph nodes. The disease has been resistant to various therapeutic approaches. Conclusions: Our case provides long‐term follow‐up of a patient with plasmacytosis and illustrates the chronic progressive course of this disease over a 10‐year course with unique involvement of the temporal artery and gastrointestinal mucosa.

鼻前庭に生じた単発型若年性黄色肉芽腫の1例

An 8-year-old girl complained of a nodule in her nasal vestibule. The nodule was a well-demarcated, dome-like, nodule, reddish-purple in color and elastic soft. The nodule was surgically excised for diagnostic and cosmetic reasons. Histological examination led to a diagnosis of juvenile xanthogranuloma. Juvenile xanthogranuloma is the most common type of non-Langerhans cell histiocytosis. It appears as benign, reddish-yellow, solitary or multiple nodules on the skin, commonly on the face, neck, scalp, or upper trunk. Xanthogranuloma occurs most frequently in infants and children, although adults may also be affected. It is not associated with metabolic abnormalities, hyperlipemia or diabetes but sometimes presents in association with neurofibromatosis and juvenile chronic myelogenous leukemia. No treatment is required because of its self-healing character, although isolated xanthogranulomas are often excised for diagnostic or cosmetic reasons. Xanthogranulomas that cause functional disorder may also be excised. Histologically, histiocytes densely infiltrate mainly the dermis. The cellular infiltrate includes giant cells, Touton cells, lymphocytes, eosinophils and neutrophils. The pathogenesis of xanthogranulomas is not clear, although it is generally considered a reactive granuloma caused by an unknown stimulus. Some reports have described isolated xanthogranulomas occurring at the site of an operation scar or insect bite, suggesting that an external stimulus may be involved in the pathogenesis of some xanthogranulomas. Xanthogranulomas in extracutaneous lesions and visceral involvement have also been reported, the most common extracutaneous site being the eye. Xanthogranulomas in the ear-nose-throat area are relatively rare. To our knowledge, the formation of a xanthogranuloma in the nose, especially in the nasal vestibule, is very rare. We report a rare case of isolated juvenile xanthogranuloma occurring in the nasal vestibule. We believe that an external stimulus may have been involved in the pathogenesis of xanthogranuloma in the present case, since children often touch their nasal vestibules with their fingers.

Uncommon histiocytic disorders: The non‐Langerhans cell histiocytoses

Histiocytic disorders are currently identified by their component cells. The non-Langerhans Cell Histiocytoses (non-LCH) are a group of disorders defined by the accumulation of histiocytes that do not meet the phenotypic criteria for the diagnosis of Langerhans cells (LCs). The non-LCH consist of a long list of diverse disorders which have been difficult to categorize. A conceptual way to think of these disorders that make them less confusing and easier to remember is proposed based on immunophenotyping and clinical presentation. Clinically the non-LCH can be divided into 3 groups, those that predominantly affect skin, those that affect skin but have a major systemic component, and those that primarily involve extracutaneous sites, although skin may be involved. Immunohistochernically many of the non-LCH appear to arise from the same precursor cell namely the dermal dendrocyte. Juvenile Xanthogranuloma (JXG) is the model of the dermal dendrocyte-derived non-LCH. Other non-LCH with differing clinical presentation and occurring at different ages but with an identical immunophenotype appear to form a spectrum of the same disorder, deriving from the same precursor cell at different stages of maturation. They should be considered as members of a JXG family. Non-JXG family members include Sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease). The non-LCH can be classified as JXG family and non-JXG family and subdivided according to fairly clear-cut clinical criteria. Utilization of this type of approach will allow better categorization, easier review of the literature and more accurate therapy decision-making.