Langerhans Cell Histiocytosis

Histiocytosis X LANGERHANS CELL HISTIOCYTOSIS

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Histiocytosis X LANGERHANS CELL HISTIOCYTOSIS (HISTIOCYTOSIS X; LANGERHANS CELL DISEASE; IDIOPATHICHISTIOCYTOSIS; EOSINOPHILIC GRANULOMA; LANGERHANSCELL GRANULOMA) Estimates of its incidence in the general population range from 1 to 4 cases per million annually.

Soft Tissue Sarcomas of Oral Cavity LANGERHANS CELL HISTIOCYTOSIS The term histiocytosis X was introduced as a collectivedesignation for a spectrum of clinicopathologic disorderscharacterized by proliferation of histiocyte-like cells thatare accompanied by varying numbers of eosinophils,lymphocytes, plasma cells, and multinucleated giantcells. The distinctive histiocytic cells present in this lesionhave been identified as Langerhans cells, and many believe that the condition is best designated as Langerhanscell histiocytosis.

Langerhanscell histiocytosis it has been debated whether Langerhans cell histiocytosis represents a nonneoplastic condition or atrue neoplasm. Studies examining the clonality of thelesional cells of this condition have shown this to be a monoclonal proliferation, a finding that is more consistentwith a neoplastic process. BRAF mutations have been identified in 40% to 60% of Langerhans cell histiocytosis lesions, and this oncogene has been implicated in uncontrolled cell division related to several other neoplasms.

Histocyte

Langerhanscell histiocytosis The clinicopathologic spectrum traditionally considered under the designation of Langerhans cell histiocytosis includes the following: Monostotic or polyostotic Eosinophilic Granuloma ofbone-solitary or multiple bone lesions without visceral involvement . Chronic disseminated histiocytosis-a disease involving bone, skin, and viscera (Hand-Schuller-Christian disease) Acute disseminated histiocytosis-a disease with prominent cutaneous, visceral, and bone marrow involvement occurring mainly in infants (Letterer-Siwe disease)

Langerhanscell histiocytosis Monostotic or polyostotic eosinophilic granuloma of bone solitary or multiple bone lesions without visceral involvement. Chronic disseminated histiocytosis a disease involving bone, skin, and viscera (Hand-Sch ller- Christian disease). Acute disseminated histiocytosis a disease with prominent cutaneous, visceral, and bone marrow involvementoccurring mainly in infants (Letterer-Siwe disease). The common Histopathologic feature in all above diseases is Langerhans cell

Langerhanscell histiocytosis It is difficult to categorize many patients into one of these classic designations because of overlapping clinical features. The often-cited Hand-Sch ller-Christian triad bone lesions, exophthalmos, and diabetes insipidus is present in only a few patients with chronic disseminated disease. It is widely believed that the traditional designations of Hand-Sch ller-Christian and Letterer-Siwe disease serve no useful purpose and should be discontinued.

New classification Single organ involvement typically bone or skin Unifocal disease Multifocal disease Multi-organ involvement No organ dysfunction Organ dysfunction Low-risk (skin, bone, lymph nodes, and/or pituitary gland) High-risk (lung, liver, spleen, and/or bone marrow)

Langerhanscell histiocytosis Although Langerhans cell histiocytosis may be encountered in patients over a wide age range, more than 50% of all cases are seen in patients younger than age 15. Although some series have reported a male predilection, overall the sexes appear to be equally affected. Bone lesions, either solitary or multiple, are the most common clinical presentation. Lesions may be found in almost any bone, but the skull, ribs, vertebrae, and mandible are among the most frequent sites.

Langerhanscell histiocytosis . Children younger than age 10 most often have skull and femoral lesions; patients over age 20 moreoften have lesions in the ribs, shoulder girdle, and mandible. The jaws are affected in 10% to 20% of all cases. Dull pain and tenderness often accompany bone lesions. Adult patients with solitary or multiple bone lesions may have lymphadenopathy but usually do not have significant visceral involvement.

Langerhanscell histiocytosis Radiographic Features Radiographically, the lesions often appear as sharply punched-out radiolucencies without a corticated rim, but occasionally an ill-defined radiolucency is seen. Bone involvement in the mandible usually occurs in the posterior areas, and a characteristic scooped out appearance may be evident when the superficial alveolar bone is destroyed.

Langerhanscell histiocytosis Radiographic Features The resulting bone destruction and looseningof the teeth clinically may resemble severe periodontitis Extensive alveolar involvement causes the teeth to appear as if they are "floating in air"

Ulcerative or proliferative mucosal lesions or a proliferative gingival mass may develop if the disease breaks out of Occasionally, this process may involveonly the oral soft tissues. Lesions also can occur within the body of the mandible or maxilla, where they may simulate a periapical inflammatory condition. 16

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Langerhanscell histiocytosis Histopathologic Features The bone lesions of patients with Langerhans cell histiocytos!s show a diffuse infiltration of large, pale- staining mononuclear cells that resemble histiocytes. These cellshave indistinct cytoplasmic borders and rounded orindented vesicular huclei. Varying numbers of eosinophilsare typically interspersed among the histiocyte-likecells. Plasma cells, lymphocytes, and multinucleated giant cells are often seen, and areas of necrosis and hemorrhage may be present.

Langerhanscell histiocytosis Electron microscopic evaluation of lesional tissue has been the "gold standard" for many years because, ultrastructurally, Langerhans cells contain rodshapedcytoplasmic structures known as Birbeck granules, which differentiate them from other mononuclear phagocytes.

What is CD? CD is an abbreviation for cluster of differentiation . CD molecules are cell surface markers which are very useful for the identification and characterization of leukocytes and the different subpopulations of leukocytes. ... The number of CD markers has grown constantly and was expanded to other cell types.

Langerhanscell histiocytosis Histopathologic Features Immunohistochemical procedures are now used to identify the Lesional Langerhans cells because of their immunoreactivity with antibodies directed against either CD-1a or CD-207 (langerin), and both markers are specific for Langerhans cell.

Langerhanscell histiocytosis Histopathologic Features

Treatmen Accessible bone lesions, such as those in the maxilla andmandible, are usually treated by curettage. Low doses ofradiation may be employed for less accessible bonelesions, although the potential for induction of malignancysecondary to this treatment is a concern inyounger patients. Intralesional injection with corticosteroidshas also been reported to be effective in somepatients with localized bone lesions.

Langerhanscell histiocytosis Histopathologic Features Prognosis Infrequently, the regression of localized histiocytosis has been reported. The prognosis for bone lesions in the absence of significant visceralinvolvement is generally good; however, progression ordissemination of the disease may occur,particularly forpatients who have 3 or more bones affected.In general, the prognosis is poorer for patientsin whom the first sign of the disease develops at a veryyoung age and somewhat better for patients who areolder at the time of onset. apparent spontaneous Langerhans cell

EWING SARCOMA Ewing sarcoma is a malignant neoplasm composed of small, undifferentiated round cells. In the United States, the annual incidence is approximately 1 per million population.Although rare, Ewing sarcoma is the second most common primary malignant bone tumor in pediatric patients after osteosarcoma.

EWING SARCOMA The histogenesis of Ewing sarcoma is unknown. Investigators previously have hypothesized that the tumor originates from the neural crest. However, current evidence favors an origin from mesenchymal stem cells with potential for limited neural differentiation. In particular, more than 85% of cases demonstrate the translocation t(11;22) (q24;q12).

EWING SARCOMA Clinical and Radiographic Features Most patients with Ewing sarcoma are adolescents, and the median age at diagnosis is 15 years. However, advances in molecular diagnosis have led to a recent increase in the number of cases diagnosed in young adults. There is a slight male predominance, and the majority of patients are white.Osseous lesions most frequently involve the long bones,pelvis, and ribs. The most common clinical findings are pain and swelling. Fever, leukocytosis, and an elevated erythrocyte sedimentation rate also may be present in advanced disease .

EWING SARCOMA Jaw involvement is more common in the mandible than the maxilla and may result in paresthesia and tooth mobility. The nonspecific clinicoradiographic presentation may lead to a misdiagnosis of odontogenic osteomyelitis. infection or

EWING SARCOMA The tumor often penetrates the cortex, resulting in a soft tissue mass overlying the affected area of the bone.

EWING SARCOMA Radiographically, most osseous lesions appear as illdefined radiolucencies, although a mixed radiolucent and radiopaque pattern also is possible. Cortical destruction or expansion may or may not be present. The characteristic onionskin periosteal reaction, commonly observed in Ewing sarcoma of long bones, seldom is seen in jaw lesions. Although plain radiography often is used for initial evaluation, CT and MRI are superior for assessing lesion extent.

EWING SARCOMA

EWING SARCOMA Histopathologic Features Ewing sarcoma composed of broad sheets of small, monotonous, round cells with well-delineated outlines and ill-defined cellular borders In some cases, variable- sized nests of tumor cells are separated by fibrovascular septa, creating a lobular Extensive necrosis hemorrhage are common. typically is nuclear pattern. and

EWING SARCOMA

EWING SARCOMA Ewing sarcomas typically exhibit cytoplasmic periodic acid-Schiff (PAS)-positive glycogen granules and membranous immunoreactivity for CD99 (MIC2), although these findings are nonspecific. Identification of characteristic chromosomal translocations by reverse transcription polymerase chain reaction (RT-PCR) or fluorescence in situ hybridization (FISH) may aid in confirming the diagnosis.

Treatment Treatment usually consists of multidrug chemotherapy with surgery and/or radiotherapy. Systemic chemotherapy typically is indicated, because seemingly localized disease often is associated with occult micrometastases.

EWING SARCOMA Prognosis With the development of modern multimodal therapy,the prognosis for patients with Ewing sarcoma has improved dramatically in recent decades. Current 5-year survival rates for patients with apparently localized versus metastatic disease at presentation are approximately 70% and 25% respectively. Ewing sarcoma, although lesions arising in the jaws appear to exhibit a more favorable prognosis compared to those arising in the long bones and pelvis.