Langerhans'-cell histiocytosis in adults

Guided by a long-term retrospective observation, the clinical course and treatment of Langerhans'-cell histiocytosis (LCH) in adult patients are represented. The series included 19 patients meeting the histopathologic criteria of presumptive LCH who were followed for 1.5–20 years (average 7.7 years). Most frequently, skeletal lesions (16 patients), diffuse interstitial lung infiltrates (seven patients), and pituitary gland involvement with diabetes insipidus (four patients) were present. Bone lesions of the skull and axial skeleton were associated with an infiltration of adjacent soft tissues in 10 of 16 patients. Liver, lymph node, and bone marrow involvement appeared sporadically. LCH was divided into localized or multifocal form. Localized disease took a benign course with remission of bone (n = 4) or lymph node lesions (n - 2). Also, in isolated pulmonary LCH (n = 2), spontaneous transition to inactive disease occurred. With the exception of isolated bone lesions (n = 27), which remained asymptomatic or showed a remission to treatment, multifocal LCH had a more aggressive course. Osseous lesions with adjacent soft tissue infiltration (n = 20) showed a relapse rate in excess of 80% independent of the treatment applied. Pulmonary involvement led to a more marked functional impairment compared to the isolated form, and systemic treatment yielded no convincing effect. In three patients with liver or bone marrow involvement, LCH showed a persistent, serious disease activity. One patient died of transition into acute monomyelocytic leukemia 18 months after diagnosis without preceding chemotherapy. In adults, LCH seems to be limited to a few organ systems. Multifocal LCH represents the more aggressive form with unfavorable prognosis in patients with bone lesions spreading into the adjacent soft tissue and liver or bone marrow involvement. © 1997 Wiley-Liss, Inc.     

Reactivation and risk of sequelae in Langerhans cell histiocytosis

OBJECTIVE: To evaluate disease reactivation in patients with Langerhans cell histiocytosis (LCH) and its impact on adverse sequelae. MATERIALS AND METHODS: A retrospective evaluation of 300 patients diagnosed with LCH between 1987 and 2002 with complete response to initial treatment was performed. RESULTS: Mean age at diagnosis was 5.3 years. With a mean follow-up of 4.8 years, reactivation of the disease occurred in 29.7% (89/300) of the patients, with two or more reactivations in 34.8% (31/89) of those. Reactivation occurred in 17.4, 36.8, 46.5, and 53.5% of the patients with single-system unifocal disease (Group A: 161 patients), single-system multifocal disease (Group B: 53 patients), multi-system disease without (Group C: 58 patients), and with (Group D: 28 patients) risk-organ involvement, respectively. The differences between the incidence rates of Groups A and B (P < 0.0004), A and C (P < 0.0001), and A and D (P < 0.0001) were highly significant. The most common reactivation sites involved were bone, middle ear, and skin; reactivation was rare in risk organs (9.5%). The median time between initial complete response and the first reactivation episode was 1 year for Group A, 1.3 years for Group B, and 9 months for Groups C and D. Most reactivation episodes (88%) occurred within the first 2 years of follow-up. Adverse sequelae were recognized in 242/300 patients: 71% (49/69) of patients with and 25.4% (44/173) without reactivations developed these adverse sequelae (P < 0.0001), respectively. Sites most commonly showing sequelae were bone, middle ear, and hypothalamus (Diabetes Insipidus). CONCLUSIONS: Incidence of reactivation correlates with the stage of the disease at diagnosis. Incidence of sequelae correlates with the occurrence of reactivations.     

Multifocal osteosarcoma: an unusual presentation

PURPOSE: Report the unusual presentation, clinical course, and cytogenetic abnormalities in a child with multifocal osteosarcoma. PATIENTS AND METHODS: A 10-year-old boy had multifocal osteosarcoma involving the entire skeleton, pleura, bone marrow, and lungs. He had marked anemia, thrombocytopenia, and severe hypocalcemia at diagnosis. RESULTS: Despite aggressive chemotherapy, he died from progressive disease 1 month after diagnosis. Cytogenetic analysis of tumor cells within the pleural fluid showed multiple chromosomal abnormalities with amplification of the c-myc oncogene. CONCLUSION: Multifocal osteosarcoma should be considered in the differential diagnosis of a child with pancytopenia and multiple bone lesions. Amplification of the c-myc oncogene may have had a significant role in the pathogenesis, etiology, and rapid progression of this patient's multifocal disease. Additional studies will be needed to determine the biologic significance of c-myc amplification in multifocal osteosarcoma.     

Chronic recurrent multifocal osteomyelitis in children: report of 17 cases]

Chronic recurrent multifocal osteitis (OCRM) is a rare condition in children, of unknown aetiology, which may be misdiagnosed as osteomyelitis, arthritis or tumour. PATIENTS AND METHODS: We present a retrospective multicentric study of 17 patients (five boys and 12 girls) with an average follow-up of 7.5 years (six months-25 years). RESULTS: A spectrum of presenting features is possible, ranging from bone lesions alone to lesions combined with arthritis, palmoplantar pustulosis or psoriasis. The diagnosis was delayed from two weeks to five years. Roentgenographic evaluation was often normal at the beginning of the disease or showed nonspecific bone reactions. Radioisotope bone scans assisted in establishing the diagnosis and in identifying lesions that were initially clinically silent. Bone biopsies were performed in seven cases. Histopathological examination showed only mild inflammatory nonspecific changes. Microbiological cultures were always negative. Treatments were different according to the evolution of the disease and the hospital. There was no response to antibiotics in seven patients. The response to nonsteroidal anti-inflammatory agents and steroids was moderate and often transient. Salazopyrine and pamidronate treatment used in two patients allowed a durable remission. We lost sight of four patients, pain persisted in three in spite of treatment, it disappeared in two with treatment, mild pain persisted in five without treatment and remission occurred in three without treatment. CONCLUSION: This study clarifies the clinical and radiologic features of chronic recurrent multifocal osteomyelitis. The recognition of this rare entity is often delayed and difficulties in patient management sometimes emerge from its usual protracted course.     

Histiocytosis X in children: Patterns of disease and results of treatment

The pathologic materials and clinical courses of 36 children aged 1 month-22 years, with histiocytosis × (H-X) seen at the Philadelphia Children's Cancer Research Center from 1970 to 1979 were reviewed. The pathologic subtype of H-X was favorable (type II) in 31 patients, unfavorable (type I) in one patient, and unclassified in four patients whose specimens were limited to a skin biopsy. Sixteen patients had localized H-X involving bone (14 patients), soft tissue (1 patient), or skin only (1 patient); all are alive and well after treatment with surgery alone (12 patients), radiation therapy (RT) (3 patients), or observation (1 patient); only 1 of the 16 developed recurrent H-X. The other 20 patients presented with multifocal H-X involving the skeleton alone (3 patients); the skeleton and soft tissues other than liver (7 patients); soft tissue exclusive of the liver (3 patients); soft tissue including the liver (4 patients); or soft tissues, skeleton, and liver or multiple drugs ± RT (15 patients). Seven of the 20 patients are alive and well without recurrence at a median of 4 years after diagnosis. Nine of the 20 patients, including 3 with liver dysfunction, responded completely to initial therapy but developed recurrence; each was retreated with drugs and is alive and well at a median of 4 years. The remaining 4 patients had widespread disease with dysfunction of the liver and/or hematopoietic system at diagnosis, failed to respond, and died. We conclude that (1) patients with multiple bony lesions with or without associated soft tissue disease or skin involvement have a favorable outlook and do not require systemic chemotherapy; (2) systemic treatment also is unnecessary for patients with localized H-X since recurrence is rare; (3) drugs can benefit patients with multifocal H-X, although the optimal duration of therapy is unclear; and (4) favorable response to treatment indicates high probability of disease-free survival. However, organ dysfunction at diagnosis is ominous: four of seven patients with liver dysfunction are dead, as are all three patients who prsented with peripheral blood count depression.     

Treatment strategy for disseminated langerhans cell histiocytosis

Treatment of Langerhans cell histiocytosis (LCH) remains problematic. To test the hypothesis that rapid initiation and longterm continuation of chemotherapy can improve survival and reduce recurrence and late consequences of disseminated LCH, we have completed a prospective clinical trial (DAL HX-83). One hundred six newly diagnosed patients were stratified into three risk groups (A: multifocal bone disease [n = 28]; B: soft tissue involvement without organ dysfunction [n = 57]; C: organ dysfunction [n = 21]). All patients received an identical initial 6-week treatment (etoposide [VP-16], prednisone, and vinblastine), and continuation treatment for 1 year, slightly adapted according to stratification at diagnosis. It included oral 6-mercaptopurine and eight pulses of vinblastine and prednisone for all patients, plus VP-16 in group B and VP-16 and methotrexate in group C. Eighty-nine percent and 91% of patients in groups A and B and 67% of the most severely affected group C, achieved complete resolution of disease. The speed of resolution was rapid (median 4 months) and independent of disease severity. The frequency of recurrence after initial resolution was low (12%, 23%, and 42% in groups A, B, and C); overall fully 77% of patients have remained free of recurrence. Permanent consequences developed after diagnosis in 20% of the patients. Diabetes insipidus after initiation of treatment occurred in only 10% of patients. Mortality (9%) was limited to patients of groups B (two patients) and C (eight patients). Finally, among the 106 patients treated by DAL HX-83 none have developed a malignancy (median follow-up 6 years, 9 months). The shorter duration of active disease, low rate of recurrence and permanent consequences, and improved survival among patients with poor prognosis support the strategy of rapid initiation of a predefined prolonged treatment upon the diagnosis of disseminated LCH. © 1994 Wiley-Liss, Inc.     

Whole-body MRI of Langerhans cell histiocytosis: comparison with radiography and bone scintigraphy

Background In Langerhans cell histiocytosis (LCH) evaluation of the extent of disease is one of the major predictors of patient outcome. Historically this is undertaken using plain radiography and bone scintigraphy. Recently, whole-body (WB) MRI has been reported to be useful in detecting skeletal and extraskeletal metastases in both adults and children. Objective To evaluate the usefulness of WB MRI in patients with LCH in comparison with plain radiography and bone scintigraphy. Materials and methods In nine children (1–7 years of age; mean 3.3 years) who had a pathological diagnosis of LCH and had either plain radiography or bone scintigraphy for comparison, 43 WB MR examinations were performed. Skeletal and extraskeletal lesions of the disease on WB MRI were compared with those on plain radiography and bone scintigraphy. Results LCH showed unifocal single-system involvement in one patient, multifocal single-system involvement in three, and multifocal multisystem disease in five. WB MRI identified additional skeletal lesions in three (38%) of eight patients, compared with plain radiography, and in two (25%) of eight, compared with bone scintigraphy. WB MRI detected extraskeletal lesions of the disease in five (56%) of the nine patients exclusively, except for one patient whose lung lesions were also detected on plain radiography. In two patients, treatment was changed according to WB MRI findings. Conclusion WB MRI is a useful initial and follow-up diagnostic method to assess the extent of LCH because WB MRI not only identifies more skeletal lesions of the disease than do plain radiography and bone scintigraphy, but also detects extraskeletal lesions of the disease.     

Use of indomethacin in Langerhans cell histiocytosis

BACKGROUND: Because prostaglandin (PG) E2 has been identified in the bone lesions of Langerhans cell histiocytosis (LCH), we speculated that indomethacin, a potent PG inhibitor, may be useful in patients with symptomatic LCH involving the bony skeleton. PROCEDURE: We used indomethacin to treat patients in whom we wanted to avoid steroids or chemotherapy, or in whom these treatments did not provide complete symptom relief. Ten children with bony LCH between 1984 and 1995 were treated; six had single-system bone disease and four had multisystem disease involving the bony skeleton and other organs. RESULTS: The dose of indomethacin ranged from 1 to 2.5 mg/kg/day (9-200 mg/day) in divided doses and was given for 1-16 weeks (mean, 6 weeks). Eight patients had a complete response to treatment, defined as complete resolution of symptoms for 4 weeks. One patient was withdrawn from treatment because of concern regarding the potential of indomethacin to induce seizures and a second patient, with suppurative skin lesions overlying a lytic skull defect, did not respond. CONCLUSIONS: Indomethacin is a useful therapy for LCH involving the bony skeleton and may have a role as first-line treatment in single-system bone disease. Whether it has a specific role in slowing disease progression or merely acts as an analgesic has not yet been established.     

Risk factors for diabetes insipidus in langerhans cell histiocytosis

BACKGROUND: Diabetes insipidus (DI) is the most frequent central nervous system (CNS)-related permanent consequence in Langerhans cell histiocytosis (LCH), which mostly requires life-long hormone replacement therapy. In an attempt to define the population at risk for DI, 1,741 patients with LCH registered on the trials DALHX 83 and DALHX 90, LCH I and LCH II were studied. RESULTS: Overall 212 of 1,741 patients (12%) was reported to have DI. In 102 of 1,741 patients (6%) DI was present at diagnosis of LCH. One thousand one hundred eighty three of 1,539 patients without DI at diagnosis had follow up information. One hundred ten of these (9%) later developed DI. The risk of developing DI was 20% at 15 years after diagnosis. Multisystem disease patients at diagnosis carried a 4.6-fold risk for DI compared to single system patients. Craniofacial lesions, in particular in the "ear," "eye," and oral region were associated with a significantly increased risk for DI (relative hazard rate, RHR 1.7), independent of the extent of disease. No influence of the duration of therapy could be determined, but the duration of initial disease activity (RHR 1.5) and the occurrence of reactivations (RHR 3.5) significantly increased the risk for DI. CONCLUSIONS: Patients with multisystem disease and craniofacial involvement at diagnosis, in particular of the "ear," "eye," and the oral region carry a significantly increased risk to develop DI during their course. This risk is augmented when the disease remains active for a longer period or reactivates.     

Cat-scratch disease. An overview based on a study of 1,200 patients

This study by one individual of 1,200 patients with cat-scratch disease provides a heretofore unavailable realistic evaluation of a common infectious disease. All patients had lymphadenopathy, a prerequisite for diagnosis. Suppuration occurred in 11.8% of patients. Cat contact was established for 99.1%, and the cat was immature in the vast majority. An inoculation site, the most neglected feature in the study of the patients, was detected in 92.6%. The results of a skin test, considered as specific as the standard tuberculin test and to be safe but not standardized, was positive in 99%. The 12 patients with negative skin tests probably were tested too early in the course of the disease to have developed reactivity. Skin tests of 578 family members of patients, who served as controls, gave positive results in 18.5%. Of 60 patients with unusual manifestations, 48 had the oculoglandular syndrome of Parinaud. Other manifestations included erythema nodosum, encephalopathy, osteolytic lesions, thrombocytopenic purpura, and erythema marginatum. Most patients in this series had received antibiotics of many types during the course of the disease. None appeared beneficial. The disease is benign in character in a majority of patients. Surgical removal of involved lymph nodes or biopsy of lymph nodes or inoculation sites is not necessary for diagnosis or management. A survey of hospitals in the United States discharging more than 750 pediatric patients annually indicates that cat-scratch disease is a problem in all sections of the country.     

BCG VACCINATION AS A CAUSE OF MULTIFOCAL OSTEOMYELITIS IN A 12-YEAR-OLD GIRL

ABSTRACT. A 12-year-old girl with multifocal skeletal sclerosis has been investigated. She was BCG vaccinated at birth and developed regional lymphadenitis in her left groin at two months of age. She was healthy until approximately 10 years of age, after which deficient height and weight gain occurred. BCG-itis was diagnosed in skeleton lesions. No evidence of immunodeficiency was found in the patient. After antituberculous treatment, the skeleton lesions, previously seen at bone scan, had disappeared. There has been a dramatic effect on her weight gain, growth and general well-being.     

Primary skeletal non-Hodgkin's lymphoma in the pediatric age group

The authors discuss rare primary skeletal non-Hodgkin's lymphoma in 16 patients treated from 1973 to 1989. The symptoms of these patients related to bone lesions in 95% of the cases. These bone lesions were monostotic or polyostotic, with or without regional and distant metastases. The locations of these lesions were long bones in 13 patients, pelvic bones in seven patients, and skull and vertebral bodies in two patients. The anatomical locations of these lesions in the bones were diaphysis alone in one patient, epiphysis in two patients, metaphysis in three patients, and a combination of diaphyseal, epiphyseal, and metaphyseal lesions in seven patients. Extraskeletal involvement was present in nine patients; extraskeletal sites included regional or distant lymph node involvement in seven cases, the mediastinum in two, lung nodules in two patients, the skin and subcutaneous regions in four patients; bone marrow in three patients, and peripheral nervous system (PNS) in one patient. Two patients had stage I disease, three had stage II disease, eight had stage III disease, and three had stage IV disease. The majority of patients had large noncleaved cell diffuse lymphomas or DHL by Rappaport classification. All patients were treated with the LSA₂-L₂ protocol; six patients received radiation therapy to the affected bone, and ten patients received no radiation therapy. Three patients failed on treatment within the first 4 months of therapy. Two patients developed a second tumor, one in the radiation therapy field and the other in a patient who received no radiation therapy. Eleven patients are alive without evidence of disease, with a median observation time of 6.5 years. The event-free survival for the 16 patients receiving LSA₂-L₂ was 73%, and the lymphoma-free survival was 81%. Extension of disease to multiple sites or location of the primary site was not of prognostic significance, but the finding of central nervous system (CNS), PNS, or bone marrow disease at diagnosis was. Whether the skeletal lesions were uni- or multifocal, with regional or distant metastases, the prognosis for lymphoma-free survival was good. The role of radiation therapy for all patients and intensive treatment for earlystage disease is discussed. The authors conclude that chemotherapy is the most important modality of treatment for any stage, histology, or location of the tumor. This chemotherapy shou ld include drugs that have been shown to be effective in the treatment of pediatric lymphoma, such as cyclophosphamide, cytosine arabinoside, vincristine, methotrexate, and daunomycin, in dosages sufficient to produce marrow suppression and early recovery, allowing for continuous or intermittent therapy. Radiation therapy should be used if there is no response or progression of disease (demonstrated either clinically or by scans, confirmed by a biopsy) within the first few months of treatment. © 1992 Wiley-Liss, Inc.     

African histoplasmosis. A case

The case reported concerns a 12 year-old girl, native of the Cameroons, hospitalized in France for the treatment of the most severe disseminated type of African histoplasmosis (Histoplasma duboisii). In addition to a severe infectious syndrome, the child presented with 3 associated typical involvements: diffuse lymphadenopathy, skin lesions consisting of nodules of the face and trunk and suppurative osteo-articular lesions with an impressive radiological appearance: extensive bone lysis and metaphyseal fractures, without any sign of bone reconstruction, even after several months of treatment. This is rare a disease, but one that should be recognized, especially in its onset localized form, in a patient presenting with infectious osteoarthritis with a torpid evolution leading to the diagnosis of tuberculous or pyogenic infection, or even of osteosarcoma. The disseminated lesions may be difficult to distinguish from the multifocal bone lesions of sickle-cell disease osteomyelitis.     

De novo malignances in pediatric organ transplant recipients

A study of 10813 types of cancer that occurred in 10151 organ transplant recipients showed that the pattern of malignancies that occurred in pediatric recipients was very different from the general pediatric population and from adult recipients. Tumors (527) occurred in 512 pediatric patients (aged 18 years or less), and 9639 adults developed 10286 neoplasms. Post-transplant lymphoproliferative disease (PTLD) was the predominant neoplasm in pediatric recipients and comprised 52% of all tumors compared with 15% in adult recipients. Eighty-four percent of PTLD in the former patients presented during childhood. There was a disproportionately high incidence among nonrenal allograft recipients compared with renal recipients (81% vs. 31% of all tumors). The second most common malignancy in pediatric patients was skin cancer (19% of tumors), but this was less frequent than in adult recipients, in whom it comprised 39% of neoplasms. Only 16 pediatric patients (16%) with skin cancers developed their tumors during childhood (6 had malignant melanomas), with an average time of appearance after transplantation of 126 months (range 5.5-292). Malignant melanomas were more common in pediatric than adult recipients (12% vs. 5% of skin cancers), as were lip cancers (23% vs. 12%). Spread to lymph nodes was also more common in pediatric than in adult recipients (9% vs. 6%). Sarcomas comprised 4% of tumors compared with 1% in adults. Carcinomas of the vulva and perineum also comprised 4% of tumors. Females outnumbered males in a ratio of 8.5:1. These tumors appeared beyond childhood at an average of 142 months (range 42-262 months) post-transplantation. Other cancers observed in recipients transplanted during childhood were thyroid carcinomas (15), Kaposi's sarcomas (15), carcinomas of the liver (13), leukemias (13), carcinomas of the cervix (10), brain tumors (7), renal carcinomas (7), ovarian carcinomas (5), and miscellaneous tumors (19). Of all 527 malignancies, 314 (60%) appeared during childhood and 213 (40%) manifested themselves between the ages of 19 and 40 years. By far the most common tumor diagnosed during childhood was PTLD, which comprised 230 of the 314 (73%) malignancies.     

Primary skeletal non-Hodgkin's lymphoma in the pediatric age group.

The authors discuss rare primary skeletal non-Hodgkin's lymphoma in 16 patients treated from 1973 to 1989. The symptoms of these patients related to bone lesions in 95% of the cases. These bone lesions were monostotic or polyostotic, with or without regional and distant metastases. The locations of these lesions were long bones in 13 patients, pelvic bones in seven patients, and skull and vertebral bodies in two patients. The anatomical locations of these lesions in the bones were diaphysis alone in one patient, epiphysis in two patients, metaphysis in three patients, and a combination of diaphyseal, epiphyseal, and metaphyseal lesions in seven patients. Extraskeletal involvement was present in nine patients; extraskeletal sites included regional or distant lymph node involvement in seven cases, the mediastinum in two, lung nodules in two patients, the skin and subcutaneous regions in four patients; bone marrow in three patients, and peripheral nervous system (PNS) in one patient. Two patients had stage I disease, three had stage II disease, eight had stage III disease, and three had stage IV disease. The majority of patients had large noncleaved cell diffuse lymphomas or DHL by Rappaport classification. All patients were treated with the LSA2-L2 protocol; six patients received radiation therapy to the affected bone, and ten patients received no radiation therapy. Three patients failed on treatment within the first 4 months of therapy. Two patients developed a second tumor, one in the radiation therapy field and the other in a patient who received no radiation therapy.(ABSTRACT TRUNCATED AT 250 WORDS)     

Langerhans' cell histiocytosis (histiocytosis X): experience at the Children's Hospital of Philadelphia, 1970-1984

Sixty-four patients with biopsy-proven Langerhans' cell histiocytosis (LCH, formerly designated as histiocytosis X) were managed at the Children's Hospital of Philadelphia from 1970 through 1984. Their median age was 3 yr (range, 0.1-22 yr). Thirty-three patients had localized lesions affecting a bone (27) or soft-tissue region (6). Twenty-two patients had multifocal disease affecting bones (17) or soft, nonosseous tissues (5). None of these patients had evidence of dysfunction of liver or lungs, and none had abnormal peripheral blood cell counts. The remaining nine patients had multifocal LCH plus dysfunction of liver or lungs (6) or abnormal blood counts (3). Treatment consisted primarily of surgical excision for patients with localized lesions and of drug therapy with or without irradiation and surgery for those with multifocal disease. Recurrence was infrequent (7%) in those with localized LCH, and all survived. Recurrence was frequent (74%) in those with multifocal LCH but without organ dysfunction or abnormal blood counts, but 21 of the 22 survived. By contrast, only three of the nine patients with organ dysfunction or abnormal blood counts survived. Thus organ dysfunction and abnormal blood counts at diagnosis emerged as the major adverse prognostic factors in children with LCH.     

Central diabetes insipidus as presenting symptom of Langerhans cell histiocytosis

BACKGROUND AND OBJECTIVES: Central diabetes insipidus (CDI) is a rare disorder associated with various underlying diseases. Among the systemic diseases that may cause CDI, Langerhans cell histiocytosis (LCH) is the most common. Therefore, in patients with endocrinologically proven CDI, a comprehensive diagnostic evaluation is crucial to identify possible extracranial sites of LCH. The goal of the diagnostic evaluation is to yield histopathological proof of the underlying disease. If possible, this histopathological proof should be provided by a biopsy of extracranial lesions to avoid a potentially hazardous biopsy of the pituitary stalk. STUDY DESIGN: In this retrospective study we included 54 patients registered at the LCH study reference center in whom the onset of CDI preceded the diagnosis of LCH, and we investigated their presentation and course to define a clinical pattern characteristic for LCH. RESULTS: In 49/54 patients (91%) the detection and biopsy of extracranial lesions led to the diagnosis of LCH. The most frequently involved organs were bones, skin, and lungs; 86% of the patients with bone lesions had skull lesions. In 18% of the patients extracranial lesions were already found at presentation of CDI, in another 51% of the patients extracranial lesions were found within 1 year from onset of CDI. CONCLUSIONS: These observations underline that a comprehensive search for extracranial lesions at presentation and during the first year thereafter may help to achieve a specific diagnosis without a pituitary stalk biopsy.     

Allogeneic stem cell transplantation in a patient with relapsed Ewing sarcoma

Ewing sarcoma (ES) can express tumor antigens which can be recognized by T cells, making allogeneic stem cell transplant (SCT) a potential option for those patients with refractory disease. A 6-year old with multifocal ES developed a recurrence of pulmonary metastases and underwent an allogeneic bone marrow transplant from her human leukocyte antigen (HLA) 10/10 matched mother. During a taper of her immunosuppression, she developed grade 1 skin and oral graft versus host disease (GVHD). CT scans performed 9 months post-transplant revealed a marked decrease in the size of her pulmonary lesions compared to scans 2 months post-transplant. This case highlights the possibility of treating patients with refractory metastatic ES with allogeneic SCT.     

A randomized trial of treatment for multisystem Langerhans' cell histiocytosis

OBJECTIVE: To compare 2 active agents, vinblastine and etoposide, in the treatment of multisystem Langerhans' cell histiocytosis (LCH) in an international randomized study. STUDY DESIGN: One hundred forty-three untreated patients were randomly assigned to receive 24 weeks of vinblastine (6 mg/m(2), given intravenously every week) or etoposide (150 mg/m(2)/d, given intravenously for 3 days every 3 weeks), and a single initial dose of corticosteroids. RESULTS: Vinblastine and etoposide were equivalent (P > or = .2) in all respects: response at week 6 (57% and 49%); response at the last evaluation (58% and 69%); toxicity (47% and 58%); and probability of survival (76% and 83%) [corrected], of disease reactivation (61% and 55%), and of developing permanent consequences (39% and 51%) including diabetes insipidus (22% and 23%). LCH reactivations were usually mild, as was toxicity. All children > or = 2 years old without risk organ involvement (liver, lungs, hematopoietic system, or spleen) survived. With such involvement, lack of rapid (within 6 weeks) response was identified as a new prognostic indicator, predicting a high (66%) mortality rate. CONCLUSIONS: Vinblastine and etoposide, with one dose of corticosteroids, are equally effective treatments for multisystem LCH, but patients who do not respond within 6 weeks are at increased risk for treatment failure and may require different therapy.