Langerhan’c cell Histiocytosis

Localized skin lesion

• Topical steroids
• Topical nitrogen mustards
• Acitretin
• Psoralen plus ultraviolet A (PUVA)

Single lymph node infiltration

• Excision is the treatment of choice

Multisystem disease

• Systemic chemotherapy

– Combination of cytotoxic drugs and systemic steroids is generally effective.

Drugs used are:-

– Vinblastine

– Etoposide

– Prednisolone

– Mercaptopurine

Treatment of refractory disease

• Cladirabine (2 chlorodeoxyadenosine 2 – CDA)
• Cytosine arabinoside (Ara – c)
• Bone marrow transplant in patients with very poor prognosis

CD la [Ref. Robbins T^h/e p. 701, 702]

• Histiocytosis is a disorder of the mononuclear phagocytic system.
• Mononuclear phagocytic system consists of monoblasts, promonocytes, monocytes and tissue macrophages,
• Macrophages are transformed monocytes i.e. monocytes present in the tissues. Moncytes emigrate continuously from peripheral blood into the tissues.

Histiocyte

• The term histiocyte is synonymous with macrophage.
• In diseases of mononuclear phagocytic system the terms histiocyte and histiocytosis are used.

Langern cell histiocytosis

• Langerhans cell is macrophage and plays important role in immunity.
• It processes antigen and present it to T cells.
• Langerhans cells histiocytosis (LCH) is a clonal histiocytosis and the lesions are characterized by the presence of Langerhans cells, eosinophils and Lymphocytes in a variable number.

The various features of langerhans cells are :

• Presence of Birbeck granules (E/M – HX bodies)
• Presence of enzymes like

– a Naphthyl acetate esterase

– a Naplahyl butyrate esterase

– Acid phosphatase

• Markers like

– S-I00 positivity

– CD-la positivity’

– HCA-DR expression

All the above mentioned optionscare disorders of histiocytes.

In langerhan cell histiocytosis, bone, lymph node and skin are the most frequently affected sytems.

The most characteristic presentation is with scalp involvement.

which is erythematous with greasy scales, looking very like seborrheic dermatitis.

S100 Paraffin, peanut agglutinin, Placental alkaline phosphatase are the common used immunological markers.

Exophthalmos is present in only 10% to 30% of cases of Langerhans cell histiocytosis.

It may be unilateral or bilateral and is due to retroocular bone infiltration by Langerhans cells.

Ans. is ‘d’ i.e., Are arranged around periphery

Ans. is ‘d’ i.e., Eosinophilic granuloma

Clinical manifestations of Langerhans cell histiocytosis (Histocvtosis-X)

Letterer Siwe disease (multifocal, multisystem LCH)

o Most frequently present before 2 years of age.

o Characterized by involvement of multiple system.

o Most common presentation is cutaneous lesions resembling seborrheic dermatitis.

o Others are hepatosplenomegaly, lymphadenopathy pulmonary lesions and destructive bone lesions. o Extensive bone marrow infiltration leads to pancytopenia.

Eosinophilic granuloma (Unifocal and multifocal unisystem LCH)

o Involvement is restricted to a single system i.e., skeletal system which may be unifocal or multifical. o Most commonly effected bones are skull, vertebrae, ribs, clavicle, and femur.

3. Hand-Schuller-Christian disease

o Characterized by triad of claviral bone defects, diabetes insipidus, and exophthalmos.

Ans. is ‘a’ i.e., CD1a

o The presence of Birbeck granules in the cytoplasm of tumor cells is characteristic of Langerhans cell histiocytosis. o As Birbeck granules are not seen in all tumor cells by election microscopy the detection of S-100 and CD1a expression by immunohistochemical techniques aids in the diagnosis.

o Other immunohistochemical markers of Langerhans cell histiocytosis are HLA-DR, Langerin (CD 207), and CD 68.

Ans. is ‘d’ i.e., Gonadal involvement occurs

Peak incidence of langerhans cell histiocytosis is seen in children less than 5 years.

o Multifocal, multisystem langerhans cell histiocytosis is known as letter-sewe disease.

o Low dose radiotherapy is effective in single system disease.

Also know

Childhood histiocvtosis

o Three classes of childhood histiocytosis are recognized based on histopathological findings

Now histiocytosis is classified into :-

(i)         Histiocytosis I

(ii)       Histiocytosis II

(iii)    Histiocytosis III

o The most well known childhood histiocytosis previously known as histiocytosis X constitutes class I histiocytosis and includes the following three :‑

o Letterer – Siwe disease

(Acute fielminant disseminated disease)

o Eosinophilic granuloma

(Solitary or few indolent lesions of bone)

o Hand schuller christian disease

(Intermediate form characterized by multifocal chronic involvement and classically presents as triad of diabetes insipidus proptosis and lytic bone lesin)

o Class I histiocytosis is also known as langherhan’s cell histiocytosis.

Ans.is ‘c’ i.e., Langerhan’s cells granulomatosis

Ans. is ‘c’ i.e., Birbeck granules

Ans. is `c’ i.e., Lagherhan’s cell histocytosis

o Seborrhic dermatitis, polyuria, hepatosplenomegaly and discharge suggests the diagnosis of Langerhan’s cell histiocytosis.

Clinical manifestations of langerhans cell histiocytosis

o It has diverse clinical features. These are

1. Skeletal involvement

            It is seen in 80% of cases (75% cases present with solitary lytic lesion)

            Skull is the most common site of involvement (Presents with solitary lytic lesion)

            Involvement of spine leads to collapse of vertebral body and compression of spinal cord.

            In flat long bones the lesion is osteolytic

            Involement of mastoid bones leads to chronically infected ears.

2. Skin involement

            It is seen in 50% of patients.

            It usually manifests as seborrhic dermatitis of scalp or diaper region.

3. Hepatosplenomegaly –

a Seen in 20% of patients

q                 Manifests as jaundice and ascites.

1. Localized or disseminated lymphadenopathy
2. Exophthalmos –

            It is often B/L and is caused by retrorbital accumulation of granulomatous tissue.

6. Pulmonary infiltrates –

 Seen in 10-15% of patients

              The lesion consists of nodular infiltrates or diffitse fibrosis.

7. Endocrine Tlypopituitarism, Hypothyroidism, Diabetes insipidus

Systemic manifestations –

              Usually seen in patients affected severly

              These include fever, weight loss, malaise, irritability

o Remember these two uncommon but serious manifestations of LCH

1. Cirrhosis d/t hepatic involvement

2. Ataxia and dysarthria d/t CNS involvement

Ans. is ‘b’ i.e., Langerhans cell histiocytosis

Ans. is ‘a’ i.e., Can be associated with diabetes insipidus; ‘c’ i.e.,Birbeck’s granules in langhan’s cell

o Hand-Schuller-Christion disease (a type of histiocytosis) is characterized by triad of : –

i) Claviral bone defects                    ii) Diabetes insipidus                   iii) Exophthalmos

o There is proliferation of langerhans histiocytes (antigen presenting cells).

o LCH is associated with HLA-DR, S-100, CD la.

o Birbeck granules are present in the cytoplasm of tumor cells.

D. i.e. Testis is commonly invoved

Answer is B (Antigen presenting cells) :

Langerhan’s cells are characteristic Antigen presenting cells

• Langerhan’s cells are clear dendritic ^Q cells situated among the cells of stratum spinosum (slun). ^Q
• They are believed to be antigen processing cells. Q
• They are S100 positive ^Q on immunohistochemical studies.
• On electron microscopy: they lack melanosomes^Q contain characteristic organelle, the Birbeck’s granule.^Q

Ans. is `d.’ i.e., Torres syndrome

Langerhans cell histiocvtosis (Histiocytosis X)

• Histiocytosis X is characterized by proliferation of Langerhans histiocytes (tissue macrophages).
• It is Subdivided into three Categories:-
• Letterer-siwe syndrome
• Hand-Schuller-Christian disease
• Eosinophilic granuloma.
• Tumor cells in each are derived from dendritic cells and express S-100, CD la and HLA-DR.
• The presence of Birbeck granules in the cytoplasm is characteristic.
• Under electron microscope, Birbeck granules have a pentalaminar, rod like, tubular appearance and sometimes a dilated terminal end (tennis-rachet appearance).

Ans. is ‘b’ i.e., Langerhan’s cells

Ans. is ‘a’ i.e., Langerhans cell histiocytosis

Birbeck granules are characteristic of langerhans cell histiocytosis

Tumour cells in the langerhan’s cell histiocvtosis are derived from dendritic cells and express :­

• S-100
• CD1a
• HLA-DR
• These cells are characterized by the presence of birbeck granules in their cytoplasm unde rthe electron micro­scope, Birbeck granules have pentalaminar, rodlike tuular appearance and sometimes a dilated terminal end (tennis-racket appearance)