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Background
The histiocytoses have been known by a variety of terms. Broadly speaking, they can be divided into Langerhans and non-Langerhans cell histiocytoses. Langerhans cell histiocytoses are all defined by the presence of a unique ultrastructural organelle, the Birbeck granule. This tennis racquet shaped cytoplasmic organelle has an unknown function. Currently, the preferred term is Langerhans cell histiocytosis.
Langerhans Cell Histiocytoses (LCH)
Histiocytosis X
Eosinophilic granuloma
Hand-Schuller-Christian Disease
Letterer-Siwe Disease
Hashimoto-Pritzker Disease (Congenital Self-Healing Langerhans Cell Histiocytosis)Non-Langerhans Cell Histiocytoses
Benign Cephalic Histiocytosis
Crystal-Storing Histiocytosis
Erdheim-Chester diseaseThe International Lymphoma Study Group has identified the following classification scheme:
CATEGORY DISEASES Macrophage/Histiocytic neoplasms Histiocytic sarcoma Dendritic Cell Neoplasms Langerhans Cell Tumor
Langerhans Cell Sarcoma
Interdigitating Cell Tumor/Sarcoma
Follicular Dendritic Cell Tumor/SarcomaUnclassifiable
DISEASE Histiocytic sarcoma Langerhans cell tumor/sarcoma Interdigitating cell tumor/sarcoma Follicular dendritic cell tumor/sarcoma
Adapted from Pileri SA, Grogan TM, Harris NL, etal. Histopathology 2002;31:1-29.OUTLINE
DISEASE ASSOCIATIONS CHARACTERIZATION MYELODYSPLASTIC SYNDROME
- Langerhans cell histiocytosis associated with myelodysplastic syndrome in adults.
Billings SD, Hans CP, Schapiro BL, Martin RW 3rd, Fivenson D, Fruland JE, Moores WB, Cotton J.
Departments of Pathology and Dermatology, Indiana University School of Medicine, Indianapolis, IN.
J Cutan Pathol. 2006 Feb;33(2):171-4. Abstract quote
Background: Myelodysplastic syndrome (MDS) is a group of bone marrow disorders associated with dyplasia of myeloid elements that may have cutaneous manifestations including infections, vasculitis, Sweet's syndrome, pyoderma gangrenosum, erythema elevatum diutinum, and leukemia cutis. These cutaneous manifestations are attributed to the underlying bone marrow defect. Langerhans cell histiocytosis (LCH) is primarily a pediatric disease, and rarely LCH has been described in association with pediatric MDS. We are aware of only a single case report of LCH associated with MDS in an adult.
Methods: We report two new cases of LCH in elderly patients with underlying MDS. The specimens were examined by routine microscopy as well as immunohistochemical stains for S100 protein and CD1a.
Results: Both patients were elderly men with established diagnoses of MDS. One presented with a solitary pruritic papule while the other had a 2-year history of erythematous papules involving the trunk and extremities. Histologic examination revealed intraepidermal and dermal collections of mononuclear cells with reniform nuclei. The cells were strongly positive for S100 and CD1a, confirming their identity as Langerhans cells.
Conclusion: Cutaneous LCH may be associated with underlying MDS in adults and should be considered in the differential diagnosis of cutaneous eruptions in patients with MDS.
PATHOGENESIS CHARACTERIZATION GENERAL Differentiation of Langerhans cells in Langerhans cell histiocytosis.
Geissmann F, Lepelletier Y, Fraitag S, Valladeau J, Bodemer C, Debre M, Leborgne M, Saeland S, Brousse N.
Institut Federatif de Recherche Necker-Enfants Malades (Service d'Anatomie Pathologique EA 219, Unite Mixte de Recherche 8603 CNRS/Universite Paris-V, Paris, France.
Blood 2001 Mar 1;97(5):1241-8 Abstract quote
Langerhans cell histiocytosis (LCH) consists of lesions composed of cells with a dendritic Langerhans cell (LC) phenotype. The clinical course of LCH ranges from spontaneous resolution to a chronic and sometimes lethal disease.
We studied 25 patients with various clinical forms of the disease. In bone and chronic lesions, LCH cells had immature phenotype and function. They coexpressed LC antigens CD1a and Langerin together with monocyte antigens CD68 and CD14. Class II antigens were intracellular and LCH cells almost never expressed CD83 or CD86 or dendritic cell (DC)-Lamp, despite their CD40 expression. Consistently, LCH cells sorted from bone lesions (eosinophilic granuloma) poorly stimulated allogeneic T-cell proliferation in vitro. Strikingly, however, in vitro treatment with CD40L induced the expression of membrane class II and CD86 and strongly increased LCH cell allostimulatory activity to a level similar to that of mature DCs. Numerous interleukin-10-positive (IL-10(+)), Langerin(-), and CD68(+) macrophages were found within bone and lymph node lesions. In patients with self-healing and/or isolated cutaneous disease, LCH cells had a more mature phenotype. LCH cells were frequently CD14(-) and CD86(+), and macrophages were rare or absent, as were IL-10-expressing cells.
We conclude that LCH cells in the bone and/or chronic forms of the disease accumulate within the tissues in an immature state and that most probably result from extrinsic signals and may be induced to differentiate toward mature DCs after CD40 triggering. Drugs that enhance the in vivo maturation of these immature DCs, or that induce their death, may be of therapeutic benefit.
APOPTOSIS
- Immunohistochemical detection of the apoptosis-related proteins FADD, FLICE, and FLIP in Langerhans cell histiocytosis.
Bank MI, Gudbrand C, Rengtved P, Carstensen H, Fadeel B, Henter JI, Petersen BL.
Department of Pathology, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, DK-2100 Copenhagen O, Denmark.
J Pediatr Hematol Oncol. 2005 Jun;27(6):301-6. Abstract quote
Langerhans cell histiocytosis (LCH) is characterized by an accumulation of dendritic Langerhans cells in granulomatous lesions in various organs. The etiology of LCH remains enigmatic. Fas/APO-1/CD95 belongs to the "death receptor" family of apoptosis regulators and has been implicated in the downregulation of immune responses.
The authors examined the expression of three proteins that are engaged in the Fas signaling cascade-FADD/Fas-associated death domain-containing protein, FLICE/FADD-like interleukin-1beta-converting enzyme (both pro-apoptotic), and FLIP/FLICE-inhibitory protein (anti-apoptotic)-in lesions from LCH patients. Immunohistochemistry was performed on paraffin-embedded tissue specimens from 43 children with LCH. The infiltrates were scored according to the amount of positive pathologic Langerhans cells (pLCs). In all investigated specimens, the majority of the pLCs expressed FADD, active FLICE, and FLIP. The clinical outcome of the disease could not be correlated to the expression of the investigated proteins. This study shows a high expression of the apoptosis-related proteins FADD, active FLICE, and FLIP in pLCs.
The authors previously showed that pLCs express Fas and Fas ligand. Taken together, these findings suggest that the Fas signaling pathway may be involved in the pathogenesis of LCH.CHROMOSOMAL ABNORMALITIES
Genotypic analysis of pulmonary Langerhans cell histiocytosis.
Dacic S, Trusky C, Bakker A, Finkelstein SD, Yousem SA.
Department of Pathology, Division of Anatomic Pathology, University of Pittsburgh Medical Center, PA 15213, USA.
Hum Pathol. 2003 Dec;34(12):1345-9 Abstract quote.
Reported studies show that the systemic form of Langerhans cell histiocytosis (LCH) is a clonal expansion of Langerhans cells (LC) associated with aberrant expression of several oncogenes or tumor-suppressor genes. LCH of the lung is a heterogenous group of lesions thought to be a reactive rather than neoplastic process. The histogenesis of the LCH of the lung is uncertain, and to date there are no studies investigating its underlying molecular abnormalities.
We performed comparative genotypic analysis by using allelic loss (LOH) of polymorphic microsatellite markers associated with tumor suppressor genes. Fourteen cases of formalin-fixed, paraffin-embedded LCH of the lung were studied. Microdissection of a total of 26 nodules from 14 patients and paired reference lung tissue was performed under stereomicroscopic visualization.
To evaluate allelic loss, we used a panel of 11 polymorphic microsatellite markers that were situated at or near tumor suppressor genes on chromosomes 1p, 1q, 3p, 5p, 9p, 17p, and 22q. The PCR products were analyzed by using capillary electrophoresis to identify germline heterozygous alleles and LOH. Allelic loss at 1 or more tumor suppressor gene loci was identified in 19 of 24 nodules. The total fractional allelic loss (FAL) ranged from 6% (1q) to 41% (22q), with a mean of 22%. The FAL in individual cases ranged from 0 (7 nodules) to 57% (1 nodule). Fifteen discordant allelic losses at 1 to 3 chromosomal loci were identified in 8 patients with multiple synchronous nodules.
Our results show that LOH of tumor suppressor genes is present in the LCH of the lung, and they indicate that the putative tumor suppressor genes situated on chromosomes 9p and 22q may play a role in the development of a subset of the LCH of the lung.
Detection of molecular cytogenetic aberrations in langerhans cell histiocytosis of bone.Murakami I, Gogusev J, Fournet JC, Glorion C, Jaubert F.
Department of Pathology, INSERM U507, Pediatric Orthopedic Department, Hopital Necker-Enfants Malades, Paris, France
Hum Pathol 2002 May;33(5):555-60 Abstract quote Langerhans cell histiocytosis (LCH) is a disorder of unknown etiology that gives rise to clonal expansion of Langerhans-like cells or their precursors. The molecular basis include aberrant expression of several adhesion molecules and elevated expression of p53, c-myc, and H-ras.
To identify new locations of LCH-related oncogenes or tumor-suppressor genes, we performed comparative genomic hybridization (CGH) and loss of heterozygosity (LOH) analysis on a series of 7 bone LCH lesions. Recurrent abnormalities were found by the CGH in all cases representing losses of DNA sequences on chromosomes 1p, 5, 6, 7, 9, 16, 17, and 22q. Gain of DNA copy number was seen on chromosomes 2q, 4q, and 12. The CGH data were supplemented by LOH analysis by means of 85 polymorphic microsatellite markers distributed along chromosomes 1, 7, 9, and 22. The highest frequency of LOH was found on 1p region in 3 of 7 informative cases and on chromosome 7 in 4 cases. Allelic loss was also detected on chromosomes 9 in 2 of 7 informative cases and on 22q in 1 of 7 cases.
These results indicate that the deleted chromosomal segments may contain genes important in LCH initiation and progression.
DISEASE ASSOCIATIONS CHARACTERIZATION DIABETES INSIPIDUS
Pediatr Blood Cancer. 2005 Jul 26; [Epub ahead of print] Abstract quote
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.Diabetes insipidus in Langerhans cell histiocytosis: results from the DAL-HX 83 study.
Grois N, Flucher-Wolfram B, Heitger A, Mostbeck GH, Hofmann J, Gadner H.
St. Anna Children's Hospital, Vienna, Austria.
Med Pediatr Oncol 1995 Apr;24(4):248-56 Abstract quote
Diabetes insipidus (DI) in Langerhans cell histiocytosis (LCH) is a common complication of unclear etiology.
The incidence varies among different publications from 15% to 50%. In the prospective DAL-HX 83 study, 19 out of 199 patients (9.5%) registered with newly diagnosed LCH were diagnosed to have DI. All patients were stratified according to uniform criteria. One hundred and six patients with disseminated disease were treated with standardized polychemotherapy promptly after diagnosis. At the time of diagnosis of LCH, DI was already established in 8 out of 199 patients (4%). After diagnosis, DI occurred in only one out of the remaining 91 patients with localized disease (1%) and in 10 out of 100 remaining patients with disseminated disease (10%). In 8 patients, the onset of DI was associated with other signs of active LCH.
The cumulative risk to develop DI after a median observation time of 5 years 3 months was 11%. Retrospective analysis of clinical features revealed multisystem involvement, skull and orbital lesions, and in particular intracranial extension from osseous lesions to constitute risk factors for DI. Magnetic resonance imaging studies (MRI) were available in 12 patients and showed abnormalities of the pituitary region in 10 children.
In none of the patients with established DI was it reversed or ameliorated by any treatment. However, the rapid institution of systemic chemotherapy for disseminated disease seems to prevent the occurrence of DI and may be responsible for the low frequency of DI in the DAL-HX83 study.
Late manifestation of diabetes insipidus in "pure" cutaneous Langerhans cell histiocytosis.
Hoeger PH, Janka-Schaub G, Mensing H.
Department of Paediatrics, University of Hamburg, Germany.
Eur J Pediatr 1997 Jul;156(7):524-7 Abstract quote
We report a case of congenital Langerhans cell histiocytosis (LCH), presenting with a generalized varicelliform rash in an otherwise well newborn. No signs of organ involvement were found on repeated skeletal radiography, abdominal ultrasonography and laboratory studies. A diagnosis of "pure cutaneous" LCH was established. Skin manifestation was unusually severe and recurred during the first 20 months of life, but responded well to combination chemotherapy (methylprednisone, vinblastine) while the child continued to thrive. At the age of 2 years the patient presented with acute onset diabetes insipidus due to infiltration of the hypothalomo-pituitary stalk region. He died for reasons unknown at the age of 28 months.
CONCLUSION: "Pure cutaneous" LCH, frequently also referred to as congenital self-healing LCH, is a variable disorder which may be complicated by late organ involvement. Close follow up and thorough diagnostic evaluation is therefore mandatory.
CNS sequelae in Langerhans cell histiocytosis: progressive spinocerebellar degeneration as a late manifestation of the disease.
Cervera A, Madero L, Garcia Penas JJ, Diaz MA, Gutierrez-Solana LG, Benito A, Ruiz-Falco ML, Villa M.
Department of Pediatric Oncology, Hospital del Nino Jesus, Madrid, Spain.
Pediatr Hematol Oncol 1997 Nov-Dec;14(6):577-84 Abstract quote
Central nervous system involvement in Langerhans cell histiocytosis (LCH), formerly known as histiocytosis X, is manifested mainly by diabetes insipidus reflecting local infiltration of Langerhans cells into the posterior pituitary or hypothalamus.
We describe two patients with progressive spinocerebellar degeneration appearing 4 and 6 years after the initial diagnosis of LCH. No correlation was found between the clinical course of the disease or its treatment and the neurological impairment. An extensive search for metabolic, toxic, neoplastic, and hereditary etiologies for progressive cerebellar degeneration was negative.
LEUKEMIA Langerhans cell histiocytosis in a child while in remission for acute lymphocytic leukemia
Lenore R. Chiles, MD
Mary M. Christian, MD
Danny K. McCoy, MD
Hal K. Hawkins
Angela H. Yen, MD
Sharon S. Raimer, MDGalveston, Texas
J Am Acad Dermatol 2001;45:S233-4 Abstract quote
The occurrence of Langerhans cell histiocytosis (LCH) and malignancy in the same patient is rare. When LCH occurs concomitantly with acute leukemia, distinct temporal patterns often exist; acute myelogenous leukemia (AML) typically succeeds LCH, whereas acute lymphocytic leukemia (ALL) usually precedes it.
We report a case of LCH developing in a child while in remission for ALL. Unique features of this case include the disseminated nature of the LCH and the death of the patient from LCH rather than ALL.
LYMPHOMA CD79a(+) T-cell lymphoblastic lymphoma with coexisting Langerhans cell histiocytosis.
Li S, Borowitz MJ.
Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA.
Arch Pathol Lab Med 2001 Jul;125(7):958-60 Abstract quote
Although there is a close association between Langerhans cell histiocytosis and malignant neoplasms, simultaneous occurrence of lymphoblastic lymphoma and Langerhans cell histiocytosis in the same lymph node is an extremely rare finding.
Herein, we describe such a case in a 26-year-old woman who presented with progressive cervical lymphadenopathy.
The lymphoma cells have an immature T-cell phenotype (terminal deoxynucleotidyl transferase(+), HLA-DR(+), CD34(+), CD38(+), and CD7(+)) with expression of both CD3 and CD79a on immunohistochemical stain. The Langerhans cells are present focally with the characteristic morphologic features and immunophenotype (CD1a(+) and S100(+)). The significance of CD79a coexpression in T-cell lymphoblastic lymphoma and the association between lymphoblastic lymphoma and Langerhans cell histiocytosis are discussed.
CHARACTERIZATION Langerhans cell histiocytosis presenting in the neonatal period: a retrospective case series.
Stein SL, Paller AS, Haut PR, Mancini AJ.
Department of Dermatology, Northwestern University Medical School, Chicago, IL 60614, USA.
Arch Pediatr Adolesc Med 2001 Jul;155(7):778-83 Abstract quote
OBJECTIVES: To describe the morphologic characteristics of skin lesions, extent of extracutaneous disease, and outcomes in patients with neonatal presentation of Langerhans cell histiocytosis (LCH), and to examine clinical predictors of disease prognosis.
DESIGN: Retrospective validation cohort study. Maximum duration of follow-up was 10 years.
SETTING: A tertiary care children's hospital in Chicago, Ill.
PATIENTS: Nineteen children with cutaneous findings in the first 4 weeks of life and subsequently diagnosed with LCH based on compatible tissue histologic analysis, confirmed by electron microscopy and/or immunohistochemical analysis.
MAIN OUTCOME MEASURE: Cutaneous lesion morphologic characteristics, extracutaneous manifestations, treatments, and outcomes were tabulated and compared.
RESULTS: The most common initial skin lesion was erythematous, often crusted, vesiculopustules. Skin lesion morphologic traits did not correlate with extent of extracutaneous disease. One third of patients had disease limited to the skin and/or mucous membranes. All of these patients are alive and well, and 1 has developed diabetes insipidus. Twelve of the 19 patients had multisystem disease, and 2 died of disease. The results of a multiorgan workup performed at the time of diagnosis were predictive of which patients in this cohort manifested multisystem disease. The overall incidence of diabetes insipidus was 21%.
CONCLUSIONS: Vesiculopustular lesions are common in congenital/neonatal LCH, but the morphologic characteristics of lesions are not helpful in predicting the extent of disease. A multiorgan evaluation at the time of diagnosis may be predictive of the probability of multisystem involvement with LCH.
Fatal, multisystemic, life-threatening lymphoproliferative disorders
Christian diseaseClassic triad of exopthalmos, diabetes insipidus, and bone destruction Solitary bone lesion Langerhans' cell histiocytosis (histiocytosis X) of bone. A clinicopathologic analysis of 263 pediatric and adult cases.
Kilpatrick SE, Wenger DE, Gilchrist GS, Shives TC, Wollan PC, Unni KK.
Division of Anatomic Pathology, Mayo Clinic, Rochester, Minnesota, USA.
Cancer 1995 Dec 15;76(12):2471-84 Abstract quote
BACKGROUND. Langerhans' cell histiocytosis (LCH) of bone is a disorder of histiocytic proliferation with variable and often unpredictable behavior.
METHOD. The authors evaluated the clinical and pathologic features of 263 patients (172 children, 91 adults) with biopsy-proven LCH examined during an 80-year period at the Mayo Clinic. Only patients with bone involvement pathologically and/or radiographically were included in the study. Clinical follow-up was available for 245 patients and ranged from 3 months to 50 years (mean, 12 years; median, 10 years). Chi-square tests were used to determine associations between age, gender, extent of osseous involvement, visceral disease, and pathologic features. Survival analyses were performed by univariate and multivariate Cox regression methods.
RESULTS. Age at presentation ranged from 2 months to 71 years with a clear predominance in children. The most common presenting complaint was pain, often worse at night. The skull was the most frequent osseous site in children and adults. Diabetes insipidus was documented in 40 patients. Forty-four children developed skeletal recurrence and/or new bone lesions, 19 of whom had diabetes insipidus. Fourteen children and 3 adults died either directly or indirectly from LCH. One adult patient developed systemic amyloidosis. All but two of these pediatric patients were 3 years of age or younger at presentation. All children with hepatosplenomegaly (7 patients) and/or thrombocytopenia (9 patients) died. Nine of the 14 children who died presented initially with three or more bone lesions.
CONCLUSIONS. The clinical behavior of LCH of bone is often unpredictable; however, young age at diagnosis, hepatosplenomegaly, thrombocytopenia, and polyostotic (> or = 3 bones involved) disease are associated with a poor prognosis (P < 0.005). Recrudescence in children, but not in adults, strongly correlates with the presence of diabetes insipidus (P < 0.0005).
Department of Pathology, Children's Medical Center Dallas, Texas, USA.
The real incidence of congenital self-healing reticulohistiocytosis (CSHR) may be underreported because of its high rate of spontaneous resolution and lack of clinical recognition. Currently, there are no criteria other than clinical that can reliably distinguish CSHR from cutaneous involvement by disseminated Langerhans cell histiocytosis (LCH).
In this study we investigate the role of E-cadherin, Ki-67, and phosphorylated histone H3 (PHH3) immunohistochemical stains in distinguishing CSHR from disseminated LCH.
We found that no significant difference was seen in the histologic features and the expression of E-cadherin, Ki-67, and PHH3 between the two groups; thus supporting the theory that CSHR and LCH represent different ends of a spectrum of the same condition.
(Congenital Self-Healing Langerhans Cell Histiocytosis/
Reticulohistiocytosis)Arch Dermatol 1973;107:263
Clinical appearance resembling TORCH infection in neonates
Papules, plaques, and occasionally vesicles in an otherwise healthy child
Varies from isolated lesions in 25% of cases to widely disseminated lesions
Typically involute within weeks to months and are not associated with internal involvementCongenital "self-healing" Langerhans cell histiocytosis: the need for long-term follow-up.
Longaker MA, Frieden IJ, LeBoit PE, Sherertz EF.
Department of Dermatology, University of California, San Francisco 94143-0316.
J Am Acad Dermatol 1994 Nov;31(5 Pt 2):910-6 Abstract quote
Congenital self-healing Langerhans cell histiocytosis (CSHLCH) is a rare disorder initially seen at birth or in the newborn period with spontaneously involuting skin lesions. In contrast to other forms of Langerhans cell histiocytosis in infancy, such as Letterer-Siwe disease, the prognosis of CSHLCH is generally good.
We describe four children with widespread CSHLCH at birth. In all patients a congenital infection was initially suspected. All patients, except one who had transient lower extremity edema and pulmonary symptoms, had an uncomplicated neonatal course, and in all patients skin lesions resolved spontaneously. Two patients showed no further evidence of disease, but one had a cutaneous relapse at age 3 months, and in another a bony relapse that required systemic therapy developed at 6 months of age.
CSHLCH is usually a benign, self-limited condition, but careful evaluation for systemic disease must be performed. Long-term follow-up for evidence of relapse or progression of disease is essential.
NON-LANGERHANS CELL HISTIOCYTOSIS
Institute of Dermatological Sciences, University of Milan-Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Milan, Italy.
Histiocytic syndromes represent a large, heterogeneous group of diseases resulting from proliferation of histiocytes. In addition to the classic variants, the subset of non-Langerhans cell histiocytoses comprises rare entities that have more recently been described. These last include both forms that affect only the skin or the skin and mucous membranes, and usually show a benign clinical behavior, and forms involving also internal organs, which may follow an aggressive course.
The goal of this review is to outline the clinical, histologic, and ultrastructural features and the course, prognosis, and management of these unusual histiocytic syndromes.BONE
- Solitary Langerhans cell histiocytosis of the
sternum in a 6-year-old girl: how should it be treated?
Wilson GJ,
Versluys AB, Bax KN.
Department of Pediatric
Surgery, Wilhelmina
Children's Hospital,
University Medical
Centre, 3508 AB
Utrecht, The Netherlands.
J Pediatr Surg. 2005 Jul;40(7):e13-5. Abstract quote
We report a 6-year-old girl with Langerhans cell histiocytosis (LCH) of the sternum successfully managed with intralesional methylprednisolone. Sternal LCH is a rare condition with only 8 cases published to date.
Management has included partial sternectomy, radiotherapy, and chemotherapy. Recent literature regarding the solitary osseous focus of LCH supports conservative management with excellent outcome after intralesional steroid administration and reports of spontaneous resolution of disease.
We advocate that conservative management should also be applied to LCH of the sternum.
Langerhans cell
histiocytosis involving epiphysis of a long bone.
Caballes RL, Caballes RA Jr, McKeon JJ.
Ann Diagn Pathol. 2004 Apr;8(2):91-5 Abstract quote.
Eosinophilic granulomas of long tubular bones, a form of Langerhans cell histiocytosis, occurs in metaphyses and diaphyses with equal frequency. Epiphyseal location is unusual, with only 13 cases previously reported in the literature.
The present case involves the epiphysis of the upper end of the left femur in a 12-year-old boy with pain and limp in the affected area. Radiographic findings were an oval, radiolucent rarefaction with nonsclerotic border, measuring approximately 3.5 x 3.0 cm.
Microscopic examination identified aggregates of histiocytes, multinucleated giant cells, scattered eosinophils, and few plasma cells and lymphocytes. Ultrastructural studies demonstrated Birbeck granules within cytoplasm of histiocytes diagnostic of Langerhans cell histiocytosis.
Whether Langerhans cell histiocytosis is a neoplastic disorder or a reactive process remains controversial. The true nature of the Langerhans cell, the proliferating cells and hallmark of this disease, is likewise under scrutiny.Langerhans cell histiocytosis of the female genital tract.
Axiotis CA, Merino MJ, Duray PH.
Warren Grant Magnuson Clinical Center, Bethesda, Maryland.
Cancer 1991 Mar 15;67(6):1650-60 Abstract quote
Langerhans cell histiocytosis (LCH) of the female genital tract is rare.
Four new cases are reported, and there is a review of the 38 cases in the literature. This disease may involve the vulva, vagina, cervix, endometrium, and ovary.
Four distinct patient groups, segregated on the basis of initial presentation and subsequent anatomic extent of disease, were categorized as follows: (1) "pure" genital LCH, (2) genital LCH with subsequent multi-organ involvement, (3) oral or cutaneous LCH with subsequent genital and multi-organ involvement, and (4) diabetes insipidus with subsequent genital and multi-organ disease. Although involvement of the genital tract can occur at any age, it is most common in young adulthood. Clinically, LCH may mimic either primary neoplasia or various inflammatory lesions; the major pathologic differential diagnosis is venereal and other inflammatory diseases. The pure genital form may have a distinct nosologic position in the spectrum of LCH similar to the "pure," self-limited cutaneous histiocytosis seen in infants. There is no correlation between histologic findings and the outcome of the genital lesions. There is also no correlation between clinical presentation and/or the extent of involvement and outcome of genital lesions; complete regression, partial improvement, persistent lesions, and recurrences were seen in all four groups of patients. The treatment of genital LCH is not well defined and is highly individualized.
Therapy has included surgery, radiation, topical corticosteroids, topical nitrogen mustard, systemic chemotherapy, and combination therapy; mixed results were obtained with all treatment modalities. Although no modality has been shown to yield a superior outcome, complete surgical excision is advocated as initial therapy.
Cutaneous Langerhans cell histiocytosis of the genitalia in the elderly: a report of three cases.
Meehan SA, Smoller BR.
Department of Pathology, Stanford University School of Medicine, California, USA.
J Cutan Pathol 1998 Aug;25(7):370-4 Abstract quote
Langerhans cell histiocytosis (LCH) is a disease with a broad spectrum of clinical presentations. All of the variants have in common the proliferation of cells which are morphologically, biochemically, and immunophenotypically indistinguishable from Langerhans cells.
A retrospective study of three elderly patients revealed the unique presentation of cutaneous Langerhans cell histiocytosis limited to the genitalia.
These cases produced a diagnostic challenge because of their unusual clinical presentation and their morphological similarity to certain other entities, including extramammary Paget's disease and malignant melanoma, which may also show S-100-positive atypical cells. All three cases showed infiltrates of histiocytic-appearing cells with folded nuclei and moderate amounts of cytoplasm which involved the epidermis, dermis, or both. Immunoperoxidase studies using antibody to S-100, CD1a and CD68 in each case showed positive staining.
TRACTDigestive tract involvement in Langerhans cell histiocytosis. The French Langerhans Cell Histiocytosis Study Group.
Geissmann F, Thomas C, Emile JF, Micheau M, Canioni D, Cerf-Bensussan N, Lazarovits AI, Brousse N.
Unite d'Immunologie et d'Hematologie, Hopital Necker-Enfants Malades, Universite Rene Descartes, Paris, France.
J Pediatr 1996 Dec;129(6):836-45 Abstract quote
BACKGROUND: Langerhans cell histiocytosis (LCH) is a rare disease with a wide clinical spectrum. Although little is known of gastrointestinal involvement in LCH, it may be a major clinical problem. We investigated clinical, pathologic, and immunohistochemical features of digestive tract LCH involvement in children.
PATIENTS: Selection criteria consisted of the presence of LCH with digestive symptoms, and histologic confirmation of gastrointestinal involvement. Seven children (2%) met the criteria among 348 cases of LCH in a French national retrospective survey from 1983 to 1993. Two children whose LCH was diagnosed in 1994 were also selected.
RESULTS: Nine children with LCH and digestive tract involvement were studied. Clinical features at presentation included skin (9/9) and mucosal (4/9) involvement, failure to thrive (5/9), diarrhea (7/9), bloody stools (4/7), vomiting (4/9), and hypoalbuminemia (8/9). Five of the nine children died; factors associated with a poor prognosis included young age, organ dysfunction (stage 4), and need for parenteral nutrition. Unlike control biopsy specimens, LCH cells of children with digestive tract involvement disclosed expression of the mucosal homing receptor integrin alpha 4 beta 7 on frozen skin and digestive tract biopsy specimens.
CONCLUSION: Cutaneous, mucosal, and digestive tract involvement in LCH is a clinicopathologic entity. The prognosis and treatment of LCH depend on the extent of the disease; therefore the treatment of these disseminated forms should not be delayed. Thus children with cutaneous LCH and digestive symptoms should undergo digestive tract biopsies. Studies of homing receptors may contribute to our understanding of the mechanisms of dissemination in LCH.
Colon involvement in Langerhans' cell histiocytosis.
Nanduri VR, Kelly K, Malone M, Milla P, Pritchard J.
Department of Haematology and Oncology, Great Ormond Street Hospital for Children, London, United Kingdom.
J Pediatr Gastroenterol Nutr 1999 Oct;29(4):462-6 Abstract quote
BACKGROUND: Langerhans' cell histiocytosis (LCH), a granulomatous disorder of unknown cause, most often affects the bony skeleton and skin. Obvious gut involvement is uncommon, and colon involvement has been cited in only a small number of case reports, probably because most patients who have LCH with diarrhoea and/or failure to thrive are not investigated by colonoscopy and biopsy. The current study was conducted to determine the incidence of symptomatic colon involvement among patients with multisystem LCH treated at a single institution.
METHOD: A retrospective review of cases in hospital records and the literature.
RESULTS: Of the 275 children with LCH in the database, 5 were identified as having biopsy-confirmed colonic involvement. Another 14 cases were identified by a literature review.
CONCLUSION: Colonic involvement in patients with multisystem LCH is probably more common than currently recognised. In addition to the other investigations recommended by the Writing Group of the Histiocyte Society, it is recommended that patients with any symptoms suggestive of gut involvement undergo colonoscopy and biopsy of the colonic mucosa.
Langerhans cell histiocytosis of the thyroid: a report of two cases and review of the literature.
Behrens RJ, Levi AW, Westra WH, Dutta D, Cooper DS.
National Cancer Institute, Bethesda, Maryland, USA.
Thyroid 2001 Jul;11(7):697-705 Abstract quote
Langerhans cell histiocytosis (LCH) is a monoclonal disease of histiocytes that can involve many or very few organ systems. It is a relatively benign disorder with a 3% mortality in adults. LCH rarely involves the thyroid gland. We report two cases, both presenting in males with a goiter. Both patients were treated with subtotal thyroidectomy. The first patient also received radiotherapy to his thyroid bed and scalp.
We summarize the prior reported cases of LCH involving the thyroid and review the current treatment modalities used for LCH.
Mod Pathol 2001;14:111-115
Case report
Document histologically, for the first time, concurrent involvement of the thyroid and parathyroid glands by LCH. A young Chinese woman with a history of diabetes insipidus and hypogonadism underwent a total thyroidectomy for enlarged thyroid gland secondary to LCH causing airway obstruction. Microscopic examination of the excised specimen disclosed CD1a- and S-100–positive LCH cells involving the thyroid and parathyroid glands.Conclusion:
In a patient with LCH affecting the thyroid gland, parathyroid gland disease should be suspected when the serum calcium levels are depressed in association with an inappropriate serum parathyroid hormone level, such as a normal parathyroid hormone level in this case.Pulmonary Langerhans' Cell Histiocytosis Molecular Analysis of Clonality
Samuel A. Yousem, etal.
Am J Surg Pathol 2001;25:630-636 Abstract quote
Pulmonary Langerhans' cell histiocytosis (LCH) is a form of Langerhans' cell disease that primarily affects smokers in the third to fifth decade. Extrapulmonary manifestations are rare. Its clinical course is typically characterized by stabilization or regression of bilateral micronodular infiltrates seen on chest radiographs; progression to honeycomb fibrosis is rare.
Because the clinical course of pulmonary LCH is distinct from systemic multiorgan LCH, currently thought to be a clonal proliferative disorder, we examined the X-linked polymorphic human androgen receptor assay (HUMARA) locus to assess clonality in female patients with one or more discrete LCH cell nodules in open lung biopsies. Langerhans' cells (LCH cells) were excised from formalin-fixed, paraffin-embedded tissue by microdissection to assure a relatively pure cellular population, and studies for differential methylation patterns at the HUMARA locus were performed.
Twenty-four nodules in 13 patients were evaluated. Seven (29%) were clonal and 17 (71%) were nonclonal. Of six cases with multiple discrete nodules, three (50%) showed a nonclonal LCH cell population. In one biopsy with five nodules, two nodules were clonal with one allele inactivated, one nodule was clonal with the other allele inactivated, and two nodules were nonclonal.
In contrast to systemic LCH, pulmonary LCH appears to be primarily a reactive process in which nonlethal, nonmalignant clonal evolution of LCH cells may arise in the setting of nonclonal LCH cell hyperplasia. Cigarette smoking may be the stimulus for pulmonary LCH in contrast to other forms of LCH.
LYMPH NODE
Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Twenty cases of Langerhans cell histiocytosis (LCH) involving lymph nodes with no other sites of disease are presented. The patients were 12 men and 8 women between 3 months and 68 years of age. Seven patients were younger than 11 years; the other 13 patients were older than 16 years. Clinically, all patients presented with lymphadenopathy and underwent excisional biopsy; clinical and imaging studies did not reveal abnormalities in other organs. Cervical lymph nodes were most commonly involved; other lymph nodes involved included axillary, inguinal, and supraclavicular.
Histologically, LCH in lymph nodes had 3 main architectural patterns: (1) preserved nodal architecture with subtle involvement, (2) subtotal effacement of nodal architecture, and (3) total effacement of nodal architecture. There was a gradient of involvement by LCH from focal sinus involvement to diffuse sinus involvement and from focal paracortical involvement to diffuse paracortical involvement. In some cases, focal involvement was initially unrecognized because of the subtle nature of the changes in the lymph node, posing difficulties for diagnosis. Langerhans cells in the involved areas showed strong positivity by immunohistochemical studies for S100 protein and CD1a in all 11 cases assessed.
In conclusion, LCH can initially manifest clinically with involvement limited to lymph nodes. Recognition of the different patterns of LCH, particularly cases with subtle involvement, is important for recognizing this disease and separating LCH from other more common causes of lymphadenopathy.
- Langerhans cell histiocytosis presenting as blueberry muffin baby.
Shaffer MP, Walling HW, Stone MS.
Department of Dermatology, University of Iowa Hospitals and Clinics, Iowa City, Iowa, USA.
J Am Acad Dermatol. 2005 Aug;53(2 Suppl 1):S143-6. Abstract quote
Blueberry muffin baby is a descriptive term for purpuric lesions reflective of extramedullary hematopoeisis. The clinical lesions most commonly result from intrauterine infections, such as rubella and cytomegalovirus, and less commonly with malignancy and hematologic disorders. Langerhans cell histiocytosis is a clonal proliferation of dendritic histiocytes in the skin. This has very rarely been associated with a blueberry muffin presentation.
We report the case of a newborn with typical lesions of cutaneous hematopoiesis and lytic bone lesions related to Langerhans cell histiocytosis. At birth, approximately 40 2 mm to 5 mm purpuric, nonblanching macules were scattered on the trunk, extremities, and soles of our patient. Laboratory studies were unremarkable and cultures were negative. Skin biopsy showed a dermal proliferation of histiocytes staining positive for S100 and Cd1a. Pediatric bone surveys, chest radiographs, and computed tomography scans of the head were normal.
Six months later, the skin lesions had resolved, but radiographs revealed lytic bone lesions of the right tibia, right ilium, and left pubic ramus, consistent with skeletal Langerhans cell histiocytosis.Adult onset folliculocentric langerhans cell histiocytosis confined to the scalp.
Hancox JG, James AP, Madden C, Wallace CA, McMichael AJ.
*Department of Dermatology, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, USA.
Am J Dermatopathol. 2004 Apr;26(2):123-6. Abstract quote
Langerhans cell histiocytosis (LCH) is a pleomorphic disease entity characterized by local or disseminated atypical Langerhans cells found most commonly in bone, lungs, mucocutaneous structures, and endocrine organs. Cutaneous disease occurs in approximately one quarter of all cases. Cutaneous findings include soft-tissue swelling, eczematous changes, a seborrheic dermatitis-like appearance, and ulceration.
We report a rare case of LCH confined to the scalp with folliculocentric infiltrates. This 32-year-old male patient presented with follicularly based erythema, scale, and pustules unresponsive to topicals and oral antibiotics. The patient's lesions mimicked lichen planopilaris and folliculitis decalvans during the disease process.
On hematoxylin and eosin stain, scalp biopsy showed a perivascular interstitial patchy lichenoid mononuclear cell infiltrate that focally abutted follicular infundibula. Prominent mononuclear cells having reniform nuclei were present, and immunoperoxidase stains for CD1a confirmed Langerhans cell differentiation. Serological and imaging workup failed to display systemic involvement.Langerhans cell histiocytosis presenting as a varicelliform eruption over the entire skin.
Johno M, Oishi M, Kohmaru M, Yoshimura K, Ono T.
Department of Dermatology, Kumamoto University School of Medicine, Japan.
J Dermatol 1994 Mar;21(3):197-204 Abstract quote
A boy with skin eruptions resembling varicella and specific for Langerhans cell histiocytosis (LCH) is reported. At his initial visit when he was four months old, vesiculopustular lesions were present over the entire body; these had first appeared on the third day post partus.
Histopathological, immunohistochemical, and electron microscopical examination confirmed the Langerhans cell phenotype and Birbeck granules in the responsible cells. He also had hydronephrosis, recurrent fever, and cutaneous bacterial infections. His parents refused further medical treatment and he died of diarrhea with cachexia about two years later.
LCH may present diagnostic difficulties by manifesting as a skin eruption which resembles varicella.
THYROID
- Langerhans cell histiocytosis presenting as a thyroid gland mass.
Elliott DD, Sellin R, Egger JF, Medeiros LJ.
Division of Pathology and Laboratory Medicine, The University of Texas, MD Anderson Cancer Center, Houston, TX 77030, USA.
Ann Diagn Pathol. 2005 Oct;9(5):267-74. Abstract quote
We report 2 cases of Langerhans cell histiocytosis (LCH) presenting as a thyroid mass. The first case is a 45-year-old woman with a 13-year history of diabetes insipidus who presented with an enlarging thyroid mass with substernal extension. The second case is a 29-year-old man who presented with an enlarging thyroid mass and skin lesions.
Histologic evaluation of the thyroid gland in both cases revealed extensive involvement by LCH, confirmed by immunohistochemical analysis showing Langerhans cells that were positive for CD1a and S-100 protein. Langerhans cell histiocytosis can rarely involve the thyroid gland in adults, and we have identified 30 cases reported in literature. Most patients had evidence of LCH involving other anatomic sites, as was true in these 2 cases, and the diagnosis was initially established by examination of other sites in a subset of patients.
Affected patients frequently have diabetes insipidus, as was true in case 1. Thyroid gland involvement as the initial presentation of LCH is a rare phenomenon that can result in misdiagnosis.
HISTOLOGICAL TYPES CHARACTERIZATION General Lancet, 1987; I: 208–9
Under the recommendation of the Writing Group of the Histiocyte Society, a definitive diagnosis of LCH can only be rendered when either there is demonstration of Birbeck granules on electron-microscopic study or there is the demonstration of CD1a expression with appropriate histological settings
Infiltrated by sheets and islands of histiocyte-like cells containing vesicular nuclei with an indented, notched, grooved or "coffee bean"-shaped appearance, one or two nucleoli, and abundant lightly eosinophilic to eosinophilic cytoplasm
Some binucleated and occasional multinucleated cells may be present
Eosinophils present in variable numbers
Accompanying lymphocytes that formed fairly dense aggregatesVARIANTS Langerhans cell (eosinophilic) granulomatosis. A clinicopathologic study encompassing 50 years.
Lieberman PH, Jones CR, Steinman RM, Erlandson RA, Smith J, Gee T, Huvos A, Garin-Chesa P, Filippa DA, Urmacher C, Gangi MD, Sperber M.
Department of Pathology, Memorial Hospital, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Am J Surg Pathol 1996 May;20(5):519-52 Abstract quote
We summarize our experience with 238 cases of Langerhans cell granulomatosis (LCG), 198 of whom were followed for a median period of 10.5 years.
Our patients did well unless overtreated, and no deaths were attributed to the disorder itself. The disease may appear in unifocal or multifocal form, and treatment is based on this fact. Virtually all patients recovered completely except for occasional residual orthopedic problems or residual diabetes insipidus. Several of the patients underwent subsequent pregnancies without difficulty. The granulomas primarily occur in bone, but lung, skin, and lymph nodal involvement is not uncommon. Involvement of thyroid, thymus, and other sites is rare.
The hallmark of the disease is the accumulation of Langerhans cells (LCs). We review the pathology of LCG by histology, electron microscopy, and immunolabeling. LCs originally were identified in squamous epithelium, but these cells are part of the widespread system of dendritic cells. The latter cells, which arise from CD34+ progenitors, are specialized and efficient antigen-presenting cells for T-cell-mediated immunity. In LCG, however, the major associated cells are not T cells, but mature eosinophils: hence the original name eosinophilic granuloma. Confusion about terminology has been based upon the scanty and rather crude pathology reports in the original literature. The term histiocytosis X was meant to cover a spectrum of three diseases--eosinophilic granuloma, Hand-Schuller-Christian disease (HSC), and Letterer-Siwe disease (LS)--but HSC and LS have no basis in pathology and hence the terms are meaningless. The term HSC has become a synonym for multifocal eosinophilic granuloma (LCG). The term LS has been used in reporting a number of benign, malignant, or unknown conditions.
We prefer the term LCG to avoid confusion with the term histiocytosis X because there is evidence that the LC is not a member of the mononuclear phagocyte system and hence not a tissue macrophage, and because the use of the term "histiocyte" has become a convenience in much of the literature when reporting incompletely understood diseases.
HEMOPHAGOCYTIC LYMPHOHISTIO-CYTOSIS
Cutaneous manifestations of hemophagocytic lymphohistiocytosis.Morrell DS, Pepping MA, Scott JP, Esterly NB, Drolet BA.
University of North Carolina, Department of Dermatology, 3100 Thurston-Bowles CB#7287, Chapel Hill, NC 27514.
Arch Dermatol 2002 Sep;138(9):1208-12 Abstract quote BACKGROUND: Hemophagocytic lymphohistiocytosis is a rare, rapidly progressive, and potentially fatal disorder of activated histiocytes. The initial clinical presentation commonly includes fever, hepatosplenomegaly, and pancytopenia. Skin eruptions are described in up to 65% of patients. Information regarding the morphological features, configuration, and distribution of these eruptions is lacking and is typically reported as nonspecific and "maculopapular." The aim of this report is to better delineate the cutaneous manifestations of the disorder to assist in differentiating the process from other systemic diseases.
OBSERVATION: A case report of a neonate with hemophagocytic lymphohistiocytosis with generalized purpuric macules is described. The clinical features of 5 other patients with hemophagocytic lymphohistiocytosis at Children's Hospital of Wisconsin, Milwaukee, are summarized. Clinical images of 1 additional neonatal patient with hemophagocytic lymphohistiocytosis are presented as well. These observations demonstrate the varied cutaneous manifestations of hemophagocytic lymphohistiocytosis: erythroderma, generalized purpuric macules and papules, and morbilliform eruptions.
CONCLUSION: Awareness of cutaneous involvement can assist in the initial diagnosis of hemophagocytic lymphohistiocytosis and potentially signify recurrences.
INDETERMINATE CELL HISTIOCYTOSIS
- Indeterminate cell histiocytosis: fact or fiction?
Ratzinger G, Burgdorf WH, Metze D, Zelger BG, Zelger B.
Clinical Department of Dermatology and Venereology, Innsbruck Medical University, Innsbruck, Austria.
J Cutan Pathol. 2005 Sep;32(8):552-60. Abstract quote
Indeterminate cell histiocytosis is a rare disorder, in which the predominant cells have the characteristics of both Langerhans cells and macrophages.
We, in this study, describe 18 patients and compare them with those previously published. Most patients were adults with either solitary or multiple red-brown papules or nodules. While most lesions were confined to the skin, both conjunctival and bony involvement was seen.
Histologically, the lesions showed patterns resembling those described for xanthogranulomas, with predominantly oncocytic (nine patients), spindled (five patients), scalloped (two patients) or vacuolated (two patients) macrophages. The accompanying infiltrate was mainly lymphocytic, although eosinophils and occasionally plasma cells were seen. All lesions were positive for macrophage markers, such as KP1 (CD68) and Ki-M1p, as well as for S-100 protein and showed variable reactivity for CD1a. No Birbeck granules were seen ultrastructurally in one patient. Some patients shared features with sinus histiocytosis with massive lymphadenopathy.
It is unclear whether this disorder is a separate entity or represents various macrophage disorders identified at various time points in the inflammatory response.
Indeterminate cell histiocytosis.Rodriguez-Jurado R, Vidaurri-De La Cruz H, Duran-Mckinster C, Ruiz-Maldonado R.
Departments of Pathology (Dr Rodriguez-Jurado) and Dermatology (Drs Vidaurri-de la Cruz, Duran-Mckinster, and Ruiz-Maldonado), National Institute of Pediatrics of Mexico, Mexico City, Mexico.
Arch Pathol Lab Med 2003 Jun;127(6):748-51 Abstract quote Indeterminate cell histiocytosis is a rare disorder involving altered homing mechanisms of the cutaneous histiocytic/dendritic system. It has been described predominantly in adults, with less than a dozen cases in children.
A 13-year-old adolescent girl presented with a 4-year history of asymptomatic erythematous nodules and plaques, measuring from 1 to 5 cm in diameter, that were located mainly on the trunk and proximal portions of her limbs. A skin biopsy showed dermal diffuse infiltration of histiocytic cells. Most of the histiocytic cells were strongly positive for S100 protein. No Birbeck granules were found.
Treatment with topical steroid was ineffective. After 6 months of pure coal tar and 5% 5-fluorouracil cream, an almost total clearing of lesions was observed. An accurate diagnosis of this condition is mandatory in order to avoid unnecessary treatments. Conservative management is also discussed.Cutaneous indeterminate cell histiocytosis: a new spindle cell variant resembling dendritic cell sarcoma
Arlene Sylvia Rosenberg1 and Michael B. Morgan2
1 Departments of Pathology, University of South Florida, Tampa, Florida, USA, 2 James A. Haley Veterans Administration Hospital, Tampa, Florida, USA
Journal of Cutaneous Pathology 2001;28 (10), 531-537 Abstract quote
Background: Cutaneous indeterminate cell histiocytosis is a rare neoplastic disorder. Its varied histological presentation and rarity have limited efforts to determine its pathogenic relationship with other histiocytic lesions and possibly, its recognition.
Methods: We report on an unusual histologic pattern of indeterminate cell histiocytosis that resembled follicular dendritic sarcoma. A battery of immunohistochemical stains and electron microscopy were performed to elucidate the phenotype of the “histiocytic” cells. Based on a review of the literature, reported cases of indeterminate cell histiocytosis are presented and the diagnostic differential of spindle-cell lesions is discussed.
Results: Spindling histiocytes were positive for S-100 and CD1a. The monocytic/macrophage marker, CD68, and the dendritic cell marker, CD21, were negative. Electron microscopy failed to reveal Birbeck granules.
Conclusions: Relatively few reports of indeterminate cell histiocytosis exist, some of which include discussion of potential overlaps with the non-X histiocytoses. Although the presence of prominent spindling in our case expanded the differential to include non-histiocytic disorders, the identified histiocytes unequivocally fulfilled the criteria of S-100 and CD1a positivity without demonstrable Birbeck granules.
- Indeterminate cell histiocytosis: a rare histiocytic disorder.
Manente L, Cotellessa C, Schmitt I, Peris K, Torlone G, Muda AO, Romano MC, Chementi S.
Department of Dermatology, University of L'Aquila, Italy.
Am J Dermatopathol. 1997 Jun;19(3):276-83. Abstract quote
A 64-year-old woman, otherwise healthy, presented with multiple reddish-brown, slightly yellowish papules on the face and neck, which had developed 3 years earlier. The lesions were painless and nonpruritic and varied in diameter from 1 to 5 mm.
Histological and immunohistochemical examination of cutaneous biopsies revealed a diffuse dermal infiltrate composed mainly of histiocytes which expressed both Langerhans cell as well as monocytic/macrophages cell marker characteristics. Electron microscopic studies revealed no Birbeck granules within the cytoplasm of the neoplastic cells, leading to a diagnosis of indeterminate cell histiocytosis.
Indeterminate cell histiocytosis is a very rare disease characterized by the proliferation of indeterminate histiocytes which morphologically and immunophenotypically resemble Langerhans cells but lack Birbeck granules.
Indeterminate cell histiocytosis--a clinicopathological entity with features of both X- and non-X histiocytosis.Sidoroff A, Zelger B, Steiner H, Smith N.
Department of Dermatology, University of Innsbruck, Austria.
Br J Dermatol 1996 Mar;134(3):525-32 Abstract quote An otherwise healthy 50-year-old woman presented with a 6-month history of having developed more than 100 generalized, non-confluent, reddish-brown, partially yellow-coloured papules.
A non-epidemotropic, monomorphous infiltrate of vacuolated mononuclear, and occasionally multinuclear, histiocytes, positive for factor XIIIa and macrophage markers HAM56 and KiM1p, was consistent with the clinical impression of generalized eruptive histiocytomas. However, the additional reactivity for S100 protein, in the absence of features of histiocytosis X, suggested a diagnosis of indeterminate cell histiocytosis (ICH).
Further immunohistochemical studies, performed on snap-frozen material, characterized the lesions as being diffusely positive with LN3 (HLA-DR), Leu4 (CD3) and Leu3 (CD4), the infiltrate in the upper dermis as reactive for OKT6 (CD1) and IOT6c (CD1c), and the infiltrate in the lower dermis as reactive for a variety of macrophage markers. Ultrastructural studies showed various non-specific features of histocytic disorders, but no Birbeck granules. Our findings confirm those of previous reports suggesting that ICH is a distinct histiocytic entity, characterized by immunophenotypic features of both X- and non-X histiocytoses. Generalized eruptive histiocytoma seems to be an early indeterminate stage of various non-X histiocytic syndromes including ICH, multicentric reticulohistiocytosis, xanthogranuloma and xanthoma disseminatum.
The distribution pattern of the various X/non-X histiocytic markers suggests dermal arrest of antigen-presenting cells during their physiological trafficking from the skin to the lymph nodes.
PROGRESSIVE MUCINOUS HISTIOCYTOSIS
J Cutan Pathol. 2006 Feb;33(2):166-70. Abstract quote
Progressive mucinous histiocytosis is a rare, benign, non-Langerhans' cell histiocytosis limited to the skin. Ten cases - all women - in four families and one sporadic case have been described in the literature. The disorder usually begins in childhood and progresses slowly.
We report two sporadic cases of adult-onset progressive mucinous histiocytosis in unrelated African-American women, aged 48 and 55