117: Histiocytosis

Question 1

What are the cutaneous clinical features of Langerhans cell histiocytosis (LCH)?

Answer 1

LCH presents with various cutaneous features including translucent, rose-yellow papules or papulovesicular lesions, erythematous, hemorrhagic papules and nodules, petechiae and nodulocutaneous lesions, lymphadenopathy, cutaneous nodules, and plaques.

Juvenile xanthogranuloma: solitary papules or nodules that may have a reddish-yellow appearance.
Benign capillary histiocytosis: resembles juvenile xanthogranuloma with the presence of worm-like bodies.
Generalized eruptive histiocytoma of childhood: widespread, erythematous, essentially symmetrical papules.

Question 2

What is the significance of the CD1a/S100B/CD207-positive mononuclear cells in LCH?

Answer 2

The presence of CD1a/S100B/CD207-positive mononuclear cells with beanshaped nuclei is significant because they are indicative of LCH, a rare neoplasm of dendritic cells. These cells infiltrate single-organ systems, most commonly affecting the bone, but can also involve the skin or multiple organ systems. Their identification is crucial for the diagnosis and understanding of the disease’s pathology.

Question 3

How are Langerhans cell histiocytoses (LCHs) and non-Langerhans cell histiocytoses (N-LCHs) categorized?

Answer 3

LCHs and N-LCHs are categorized into different subgroups based on their clinical features and histopathology.

LCHs include skin disorders, hematopoietic lymphohistiocytoses, cutaneous non-LCHs, juvenile xanthogranuloma, benign capillary histiocytosis, generalized eruptive histiocytoma of childhood, adult xanthogranuloma, papular xanthoma, xanthoma disseminatum, Erythelin-Chester disease, necrotic xanthogranulomatosis, hereditary progressive necrotizing histiocytosis, and progressive nodular histiocytosis. N-LCHs include single-organ system LCH and multisystem LCH.

Question 4

What are the four main clinical types of Langerhans Cell Histiocytosis (LCH)?

Answer 4

The four main clinical types of LCH are Hashimoto-Pritzker disease, Eosinophilic granuloma, Hand-Schüller-Christian disease, and Letterer-Siwe disease.

Question 5

What is the significance of the BRAF-V600E mutation in LCH?

Answer 5

The BRAF-V600E mutation is significant because it is found in approximately 60% of patients with LCH, indicating that LCH is a clonal neoplastic disorder. This mutation contributes to the pathogenesis of LCH by affecting the signaling pathways involved in cell growth and differentiation.

Question 6

What are the epidemiological characteristics of LCH in children and adults?

Answer 6

In children younger than 15 years, the annual incidence is approximately 0.7 to 4.1 cases per 1 million population. The median age at diagnosis is between 30.2 months to 5.9 years. In adults, the incidence is lower, with only 1 to 2 cases per 1 million adults.

Question 7

What factors are associated with an increased risk of developing LCH?

Answer 7

Factors associated with an increased risk of developing LCH include living in crowded conditions, lower education level, exposure to metal, granite, wood dust, or solvents in parents, family history of thyroid disease and cancer, and perinatal infections.

These risk factors should be interpreted with caution.

Question 8

How does the severity of organ involvement in LCH depend on ERK activation?

Answer 8

The severity and extent of organ involvement in LCH depend on the stage of differentiation in which ERK gets activated. Activation in a hematopoietic stem cell or undifferentiated myeloid dendritic cell leads to multisystem disease, while ERK activation in more differentiated myeloid precursors results in multifocal or unifocal disease.

Question 9

What are the two classifications of LCH based on organ involvement?

Answer 9

1. Single-system LCH: Affects approximately 55% to 65% of patients, involving only one organ system, commonly bone, skin, lymph nodes, lungs, or CNS. 2. Multisystem LCH: More than one organ system is affected by the disease.

Question 10

What are the common cutaneous findings in LCH?

Answer 10

Cutaneous findings can be identified in more than one-third of LCH cases. The most typical lesions are small, translucent rose-yellowish crusted papules or papulovesicles on the trunk and scalp. Other lesions include hemorrhagic papules, vesicles, pustules, and nail involvement.

Nail involvement can present as paronychia, onycholysis, and pigmented striae of the nail bed.

Question 11

What is the most common noncutaneous organ involved in LCH and what are some associated findings?

Answer 11

The most common noncutaneous organ involved in LCH is bone (77% of cases). Associated findings include tender masses in affected areas, radiologic workup shows lytic areas with a ‘punched out’ appearance, and involvement of the cervical vertebrae can lead to vertebra plana in children, while adults may experience asymmetric collapse of vertebrae, leading to neurologic defects.

Question 12

What is the significance of nail involvement in LCH?

Answer 12

Nail involvement in LCH can present as paronychia, nailfold destruction, and other changes. It is associated with a higher risk for multisystem LCH and may indicate a poor prognostic sign, warranting further evaluation in clinical trials.

Question 13

What are the implications of bone marrow involvement in LCH?

Answer 13

Bone marrow involvement frequently affects young children with other risk organs like the liver and spleen. It was previously suspected only in cases of significant anemia, thrombocytopenia, or neutropenia, indicating a need for careful monitoring in affected patients.

Question 14

A 5-year-old child presents with translucent rose-yellowish crusted papules on the trunk and scalp, resembling seborrheic dermatitis. What is the likely diagnosis, and what is the next step in management?

Answer 14

The likely diagnosis is Langerhans Cell Histiocytosis (LCH). The next step is a skin biopsy to confirm the presence of CD1a/S100B/CD207-positive mononuclear cells.

Question 15

A 1-year-old child presents with hemorrhagic papules and petechiae on the trunk. What is the likely diagnosis, and what is the significance of age in this condition?

Answer 15

The likely diagnosis is Langerhans Cell Histiocytosis (LCH). Children younger than 1 year are more likely to have true skin-only LCH.

Question 16

What are the serious complications associated with hepatic involvement in LCH?

Answer 16

The serious complications associated with hepatic involvement in LCH include cholestasis and sclerosing cholangitis.

In most cases, sclerosing cholangitis will not respond to chemotherapy, and liver transplantation remains the only possible treatment option.

Question 17

What is the most common endocrinopathy encountered in LCH and what are its symptoms?

Answer 17

The most common endocrinopathy encountered in LCH is diabetes insipidus. Patients present with polyuria, polydipsia, and nocturia.

The risk of developing diabetes insipidus in patients with diagnosed LCH is approximately 24%.

Question 18

What are the common manifestations of CNS involvement in LCH?

Answer 18

The common manifestations of CNS involvement in LCH include endocrine abnormalities from large pituitary tumors, most frequently diabetes insipidus, and neurodegenerative symptoms such as ataxia, dysarthria, cognitive dysfunction, and behavior changes.

Question 19

What are the key components of a complete history and physical examination for LCH?

Answer 19

Key components of a complete history and physical examination for LCH include questions regarding pain, swelling, skin rash, otorrhea, irritability, fever, loss of appetite, diarrhea, weight loss, growth failure, polydipsia, polyuria, changes in activity level, dyspnea, smoke exposure, and behavioral and neurologic changes.

Assessment of pubertal status and thorough skin and mucous membrane evaluation for presence of jaundice, pallor, edema, lymphadenopathy, ear discharge, orbital abnormalities, abnormal mucosal lesions, abnormal dentation, and soft-tissue swelling. Evaluation of liver and spleen size, and a complete neurologic evaluation is mandatory.

Question 20

What is the relationship between thrombocytopenia, anemia, and LCH outcomes?

Answer 20

When thrombocytopenia and anemia, especially in combination with hypoalbuminemia, are present, LCH is associated with a poor outcome.

Question 21

A 30-year-old smoker presents with cystic destruction of lung tissue in the upper lung fields. What is the likely diagnosis, and what is the primary risk factor?

Answer 21

The likely diagnosis is Langerhans Cell Histiocytosis (LCH) with lung involvement. Smoking is the primary risk factor.

Question 22

A child presents with diabetes insipidus and a history of LCH lesions in the facial bones. What is the significance of these findings?

Answer 22

Facial bone lesions are classified as ‘CNS-risk’ lesions and are associated with a 3-fold increased risk of developing central nervous system diseases such as diabetes insipidus.

Question 23

A patient with LCH has a liver biopsy showing sclerosing cholangitis. What is the treatment of choice?

Answer 23

Liver transplantation is the only possible treatment for sclerosing cholangitis induced by LCH.

Question 24

What are the typical histopathological findings in a skin biopsy for LCH?

Answer 24

Typical findings include dense and band-like infiltration of the papillary dermis with LCH cells, which are oval shaped with eosinophilic cytoplasm, irregular, vesicular, and infolded (kidney-shaped) nucleus. Longitudinal nuclear grooves may give a coffee bean-like appearance. LCH cells are larger than lymphocytes and mixed with neutrophils, eosinophils, lymphocytes, plasma cells, and histiocytes, especially in early lesions. Later lesions show foamy histiocytes and prominent dermal fibrosis.

Question 25

What is the significance of Birbeck granules in LCH cells?

Answer 25

Birbeck granules are organelles found in LCH cells that resemble a tennis racquet and have a zipper-like appearance along the handle. They were previously detected by electron microscopy, which was the diagnostic gold standard for LCH. However, immunohistochemical staining with CD207, which recognizes a C-type lectin associated with Birbeck granules, is now considered the most sensitive marker for diagnosis.

Question 26

What are the predictors of poor outcomes in patients with LCH?

Answer 26

Predictors of poor outcomes include involvement of at-risk organs such as the liver, spleen, and bone marrow, enlargement of the liver by more than 3 cm below the costal margins, hematopoietic involvement with severe anemia or thrombocytopenia. Previous factors like age younger than 2 years or lung involvement are no longer considered risk factors.

Question 27

What treatment strategies are recommended for LCH based on disease extent and localization?

Answer 27

Treatment strategies depend on the extent and localization of the disease and the age of the patient. Specific recommendations include: 1. Limited disease confined to bone or skin is usually not treated systemically, except for special site lesions. 2. Systemic treatment may be considered for multifocal bone lesions and CNS-risk lesions. 3. In children with LCH confined to the skin, a watch-and-wait strategy is preferred. 4. Topical corticosteroid ointments can be tried, but have shown little efficacy; a skin rash that does not respond to topical steroids is a clue for LCH.

Question 28

A patient with LCH has lesions confined to the liver and spleen. What are the prognostic implications, and what treatment should be considered?

Answer 28

Liver and spleen involvement are considered high-risk organ involvement and are associated with a poor prognosis. Systemic treatment with vinblastine and prednisolone for 12 months is recommended.

Question 29

A patient with LCH has a skin biopsy showing Birbeck granules. What is the most sensitive marker for diagnosis?

Answer 29

The most sensitive marker for LCH diagnosis is CD207 (Langerin).

Question 30

A patient with LCH has a skin biopsy showing multinucleated giant cells and marked epidermotropism. What is the diagnosis?

Answer 30

The diagnosis is Langerhans Cell Histiocytosis (LCH).

Question 31

A patient with LCH has a skin biopsy showing CD1a/S100B/CD207-positive cells. What is the next step in management?

Answer 31

Risk stratification based on organ involvement is crucial to determine the optimal treatment regimen.

Question 32

A patient with LCH has a skin biopsy showing coffee bean-like nuclei. What is the significance of this finding?

Answer 32

Coffee bean-like nuclei are characteristic of LCH cells and aid in diagnosis.

Question 33

A patient with LCH has a skin biopsy showing Birbeck granules. What is the diagnostic gold standard?

Answer 33

Immunohistochemical staining with CD207 is now the diagnostic gold standard, replacing electron microscopy.

Question 34

A patient with LCH has a skin biopsy showing a dense band-like infiltration of the papillary dermis. What is the next step in management?

Answer 34

The next step is to assess the extent of organ involvement to guide treatment.

Question 35

A patient with LCH has a skin biopsy showing CD1a/S100B/CD207-positive cells. What is the significance of these markers?

Answer 35

These markers are characteristic of Langerhans Cell Histiocytosis and confirm the diagnosis.

Question 36

What are some topical treatment options for skin lesions in LCH?

Answer 36

Topical treatment options for skin lesions in LCH include Imiquimod, Tacrolimus, intralesional corticosteroid injections, CO2 laser therapy, excision of single LCH nodules, and nitrogen mustard ointment can also be applied to treat skin lesions in adults.

Question 37

What is the recommended duration for systemic treatment in LCH based on recent trials?

Answer 37

Based on the results of the most recent LCH-III trial, patients should be treated systemically for 12 months because those treated for only 6 months have an increased frequency of early relapse.

Question 38

What is the treatment protocol for multisystem LCH involving vinblastine and prednisolone?

Answer 38

The treatment protocol consists of a 6-week induction chemotherapy phase with Vinblastine (6 mg/m² weekly intravenous bolus) and Prednisolone (40 mg/m²/day orally for 4 weeks.

Question 39

What is the recommended treatment duration for patients with LCH based on recent trials?

Answer 39

Patients should be treated systemically for 12 months because those treated for only 6 months have an increased frequency of early relapse.

Question 40

What is the treatment protocol for multisystem LCH involving vinblastine and prednisolone?

Answer 40

The treatment protocol consists of a 6-week induction chemotherapy phase with: - Vinblastine (6 mg/m² weekly intravenous bolus) - Prednisolone (40 mg/m²/day orally for 4 weeks, then tapered over 2 weeks) A subsequent therapy may include vinblastine/prednisolone with or without mercaptopurine, depending on treatment response after 6 weeks.

Question 41

What are the potential outcomes of the treatment regimen for patients with risk-organ involvement in LCH?

Answer 41

With the treatment regimen involving vinblastine and prednisolone: - 86% of patients without risk-organ involvement show a response to therapy after 6 weeks. - 66% of patients with risk-organ involvement also show a response after 6 weeks. This response is an important prognostic factor for outcome, although 50% of patients in the study did not respond to treatment.

Question 42

What are some novel therapeutic options for Non-Langerhans Cell Histiocytosis (N-LCH)?

Answer 42

Novel therapeutic options for N-LCH include: - BRAF inhibitors - MAPK inhibitors - Anti-programmed death 1 treatments - Anti-programmed death ligand 1 treatments These treatments may be successful in managing N-LCH.

Question 43

What is the next step in treatment for a patient with LCH showing a poor response to vinblastine and prednisolone after 6 weeks?

Answer 43

Salvage strategies with cytarabine, cladribine, or clofarabine should be considered.

Question 44

What is the recommended management strategy for a patient with LCH and a single bone lesion?

Answer 44

A watch-and-wait strategy can be used, or options like simple curettage or intralesional steroid injections can be considered.

Question 45

What is the significance of a skin rash unresponsive to topical steroids in a patient with LCH?

Answer 45

A skin rash unresponsive to topical steroids is considered a clue for LCH.

Question 46

What is the recommended treatment for a patient with LCH and a vertebral lesion with intraspinal soft-tissue extension?

Answer 46

Systemic treatment with vinblastine and prednisolone is recommended for 'special site' lesions like vertebral lesions with intraspinal soft-tissue extension.

Question 47

What are the characteristics of systemic forms of N-LCH compared to cutaneous forms?

Answer 47

Systemic forms of N-LCH are characterized by an accumulation of classically activated macrophages (Mϕ1), while cutaneous forms are characterized by the presence of alternatively activated macrophages (Mϕ2).

Question 48

What is the hallmark of Rosai-Dorfman disease (RDD)?

Answer 48

The hallmark of RDD is emperipolesis, which is the presence of different types of bone marrow cells, such as lymphocytes or neutrophils, found in the cytoplasm of histiocytes with a background of mature lymphocytes and plasma cells.

Question 49

What are the main clinical manifestations of Rosai-Dorfman disease (RDD)?

Answer 49

The main clinical manifestation of RDD is lymphadenopathy, particularly in the neck lymph nodes, although accumulation of histiocytes can occur in other organs such as the skin, breast, kidney, thyroid, testis, and CNS.

Question 50

What are the two major forms of Hemophagocytic Lymphohistiocytosis (HLH)?

Answer 50

The two major forms of HLH are: 1. Primary HLH: Includes familial HLH and several primary immunodeficiencies, which exhibit genetic inheritance and usually occur in infancy. - Several genetic defects in primary HLH genes such as HPLH1, perforin, UNC13D, STX11, and STXBP2 have been identified. 2. Secondary HLH: Associated with infections (e.g., Epstein-Barr virus), autoimmune disorders (e.g., juvenile idiopathic arthritis), and malignancies (mainly non-Hodgkin lymphoma).

Question 51

What is the significance of S100B in Rosai-Dorfman disease (RDD)?

Answer 51

S100B can be used as a serum marker to monitor disease progression or therapy response in patients with Rosai-Dorfman disease (RDD).

Question 52

What histopathologic hallmark should be looked for in a patient with Rosai-Dorfman Disease presenting with massive cervical lymphadenopathy?

Answer 52

The hallmark of RDD is emperipolesis, where bone marrow cells such as lymphocytes or neutrophils are found in the cytoplasm of histiocytes.

Question 53

What is the treatment of choice for a patient with Rosai-Dorfman Disease who has extranodal involvement of the breast and thyroid?

Answer 53

Surgical resection or radiotherapy for affected lymph nodes or skin lesions is the treatment of choice.

Question 54

What is the classification of a patient with HLH showing mutations in the STXBP2 gene?

Answer 54

This is classified as Primary HLH, which includes familial HLH and primary immunodeficiencies.

Question 55

What is the classification of a patient with HLH who has persistent fever and splenomegaly?

Answer 55

This is classified as Secondary HLH, which is associated with infections, autoimmune disorders, or malignancies.

Question 56

What are the key clinical features of Juvenile Xanthogranuloma (JXG)?

Answer 56

- Benign, self-healing skin disorder primarily affecting infants under 1 year of age. - 5% to 17% of children may have cutaneous lesions at birth. - 40% to 70% present during the first year of life. - Manifests as solitary and multiple papules or nodules on the face, neck, and upper trunk. - Early lesions are reddish-brown; mature lesions appear reddish-yellow. - Ocular lesions occur in up to 10% of cases, potentially affecting vision.

Question 57

What are the histopathologic findings associated with Juvenile Xanthogranuloma (JXG)?

Answer 57

- Early lesions show monomorphous, non-lipid containing histiocytic infiltrates in the dermis. - Mature lesions are characterized by foam cells, Touton giant cells, and foreign-body giant cells. - Lesional histiocytes are positive for stabilin-1 and stain for macrophage markers like CD163, CD11b, CD11c, CD36, CD68, factor XIIIa, and vimentin. - S100B and CD1a are NOT expressed.

Question 58

What is the prognosis for Juvenile Xanthogranuloma (JXG)?

Answer 58

- JXG usually resolves spontaneously over 1 to 5 years. - Ocular lesions rarely improve spontaneously and may require treatment. - Treatments include surgical excision, CO2 laser treatment, intralesional steroid injection, cryotherapy, and low-dose radiotherapy.

Question 59

How can Juvenile Xanthogranuloma (JXG) be differentiated from Langerhans Cell Histiocytosis (LCH)?

Answer 59

JXG can be distinguished from LCH by the expression of stabilin-1 and the absence of CD1a and CD207.

Question 60

What are the clinical features of Benign Cephalic Histiocytosis?

Answer 60

- Characterized by small, yellow-red or yellow-brown, asymptomatic papules on the head and neck of young children. - Tendency toward spontaneous remission. - Associated with worm-like bodies, also known as 'histiocytosis with intracytoplasmic worm-like bodies.'

Question 61

What are the histopathologic findings in Benign Cephalic Histiocytosis?

Answer 61

- Infiltrate of histiocytes closely approaching the epidermis, accompanied by scattered lymphocytes and eosinophils. - Histiocytes express the macrophage marker CD68; immunostaining for Langerhans cell markers CD1a and CD207 is negative. - Ultrastructural presence of worm-like bodies is typical.

Question 62

What challenges exist in the differential diagnosis of Benign Cephalic Histiocytosis?

Answer 62

It is difficult to separate benign cephalic histiocytosis from other forms of N-LCH, especially JXG, making it a variant of JXG.

Question 63

What is the diagnosis and prognosis for a 6-month-old infant with reddish-brown papules on the face and neck showing Touton giant cells?

Answer 63

The diagnosis is Juvenile Xanthogranuloma (JXG). The prognosis is good as JXG usually resolves spontaneously over 1 to 5 years.

Question 64

What is the first-line treatment for a patient with Hemophagocytic Lymphohistiocytosis (HLH) presenting with persistent fever, splenomegaly, and cytopenia?

Answer 64

First-line treatment includes high-dose corticosteroids, cyclosporine, and etoposide.

Question 65

What histopathologic finding is typical for a patient with Benign Cephalic Histiocytosis presenting with yellow-brown papules on the head and neck?

Answer 65

Histopathology shows histiocytes expressing CD68 but negative for CD1a and CD207, with ultrastructural worm-like bodies.

Question 66

What is the significance of elevated soluble IL-2 receptor levels in a patient with HLH?

Answer 66

Elevated soluble IL-2 receptor levels are a biological marker of HLH.

Question 67

What is the recommended treatment for ocular lesions in a patient with Juvenile Xanthogranuloma?

Answer 67

Ocular lesions require treatment, which may include surgical excision, CO2 laser treatment, or intralesional steroid injection.

Question 68

What factors contribute to a poor prognosis in a patient with HLH?

Answer 68

Poor prognosis is associated with malignancy, persistent fever, splenomegaly, and cytopenia.

Question 69

What are the clinical features of adult xanthogranuloma?

Answer 69

- Solitary and oligolesional yellow-orange papules usually appear on the face, neck, and lower arms. - Does not show spontaneous remission unlike juvenile xanthogranuloma. - No association with systemic diseases such as neurofibromatosis or leukemia. - Histologic findings of adult and juvenile forms are almost identical. - Adult xanthogranuloma has more giant cells.

Question 70

What is the clinical course and prognosis of generalized eruptive histiocytoma (GEH)?

Answer 70

- GEH usually resolves spontaneously. - Therapeutic options include surgical excision and CO2 laser. - Systemic psoralen and ultraviolet A therapy may also be considered.

Question 71

What are the histopathologic findings associated with papular xanthogranuloma?

Answer 71

- Histology shows a normal epidermis and a dense infiltration of xanthomatized macrophages interspersed by numerous Touton-type giant cells. - Immunohistochemically, mononucleated and multinucleated macrophages are positive for KiM1p. - Only giant cells are positive for CD68, and up to 50% of xanthomatized cells are positive for the lectin peanut agglutinin. Stainings for factor XIIIa and CD1a are negative.

Question 72

What are the differential diagnoses for generalized eruptive histiocytoma (GEH)?

Answer 72

- Differential diagnosis includes LCH, other forms of N-LCH, and urticaria pigmentosa. - Other N-LCHs are easily distinguished by histology.

Question 73

What are the clinical features of papular xanthogranuloma?

Answer 73

- It is a rare disease in normolipemic patients, presenting mainly as a solitary yellowish papule, more common in males. - Shows a biphasic occurrence in young adolescents and middle-aged persons. - A congenital form has been reported. - Mucous membranes may be affected in some cases, but there is no systemic involvement. - A plaquelike form can be seen as a variant.

Question 74

What is the prognosis for a patient with Adult Xanthogranuloma presenting with yellow-orange papules on the face and neck?

Answer 74

Adult Xanthogranuloma does not show spontaneous remission and requires excision or CO2 laser therapy.

Question 75

What is the prognosis for a patient with Benign Cephalic Histiocytosis presenting with papules on the head and neck?

Answer 75

Benign Cephalic Histiocytosis usually resolves spontaneously.

Question 76

What are the clinical features of Xanthoma disseminatum?

Answer 76

Xanthoma disseminatum preferentially affects male children and is characterized by the sudden appearance of small, yellow-red to brown papules and nodules that are discrete and disseminated, particularly in flexural and intertriginous areas as well as mucous membranes. It can lead to significant morbidity and mortality due to internal organ involvement and systemic associations such as central diabetes insipidus and paraproteinemias like multiple myeloma.

Question 77

What are the histopathologic findings in Xanthoma disseminatum?

Answer 77

- Early lesions show a predominance of scalloped histiocytes, while more established lesions consist mainly of foamy histiocytes with few scalloped cells. Mature lesions contain a mixture of scalloped cells, foam cells, lymphocytes, and Touton giant cells, which are positive for stabilin-1, HAM-56, HHF35, KP1, KiM1P, factor XIIIa, and vimentin, and negative for S100B and CD1a.

Question 78

What is the clinical course and prognosis of Xanthoma disseminatum?

Answer 78

Xanthoma disseminatum is a slowly progressing disease. Cutaneous lesions can be treated with CO2 laser therapy, and lesions are not very radiosensitive. Various medications, including statins, fibrates, and cyclophosphamide, have been tried with variable results. A successful therapeutic approach seems to be the administration of 2-chlorodeoxyadenosine.

Question 79

What are the clinical features of Multicentric Reticulohistiocytosis (MRH)?

Answer 79

Multicentric Reticulohistiocytosis is a rare, multisystem inflammatory disease that usually appears around the age of 50 years, but there are reports of occurrence during childhood. It is twice as common in females, with cutaneous lesions being firm, yellow-brownish papules or nodules that can reach several centimeters in size. Common clinical manifestations include cutaneous eruptions and symmetric inflammatory polyarthritis, with potential involvement of internal organs such as the lungs and heart.

Question 80

What are the histopathologic findings in Multicentric Reticulohistiocytosis?

Answer 80

Histopathology reveals mid-dermal infiltrates of mononuclear histiocytes and multinucleated histiocytes with a ground-glass appearance and a variable number of vacuolated, spindle-shaped, and xanthomatized mononuclear histiocytes. Immunohistochemical analyses are usually positive for CD45, CD68, and HLA-DR, but negative for S100B, CD1a, or HHF-35 actin.

Question 81

What is the clinical course and prognosis of Multicentric Reticulohistiocytosis?

Answer 81

The disease can be self-limited, but severe joint destruction usually results. Treatment options include surgical excision, pulsed dye laser, oral corticosteroids, methotrexate, cyclophosphamide, and tocilizumab, which have shown success in treating extensive MRH lesions. A systematic review indicated efficacy of anti-tumor necrosis factor treatment in MRH.

Question 82

What is the likely diagnosis for a 50-year-old patient presenting with symmetric inflammatory polyarthritis and firm yellow-brown papules over the joints, and what systemic associations should be considered?

Answer 82

The likely diagnosis is Multicentric Reticulohistiocytosis (MRH). Systemic associations include malignancies such as hematologic, breast, or stomach carcinomas.

Question 83

What is the recommended treatment for cutaneous lesions in a patient with Xanthoma Disseminatum presenting with systemic involvement, including the pituitary stalk?

Answer 83

Cutaneous lesions can be treated with CO2 laser therapy.

Question 84

What is the prognosis for a patient with Xanthoma Disseminatum presenting with systemic involvement?

Answer 84

Xanthoma Disseminatum is a slowly progressing disease, and systemic involvement can result in significant morbidity and mortality.

Question 85

What is the recommended treatment for a patient with MRH presenting with leonine facies due to facial lesions?

Answer 85

Treatment options include oral corticosteroids, methotrexate, cyclophosphamide, and tocilizumab.

Question 86

What is the recommended treatment for cutaneous lesions in a patient with Xanthoma Disseminatum?

Answer 86

Cutaneous lesions can be treated with CO2 laser therapy.

Question 87

What is the prognosis for a patient with systemic involvement of Xanthoma Disseminatum?

Answer 87

Xanthoma Disseminatum is a slowly progressing disease, and systemic involvement can result in significant morbidity and mortality.

Question 88

What are the recommended treatment options for a patient with MRH and leonine facies?

Answer 88

Treatment options include oral corticosteroids, methotrexate, cyclophosphamide, and tumor necrosis factor antagonists.

Question 89

What are the clinical features of Erdheim-Chester disease?

Answer 89

- Rare disease with onset in middle age. - Long bone involvement is almost universal, bilateral, and symmetrical. - Spectrum of disorders from asymptomatic bone lesions to life-threatening variants. - More than 50% of cases have extraskeletal involvement (kidney, skin, brain, lung). - Skin manifestations include xanthelasma and xanthoma in one-sixth of cases. - Yellow-brown papular and infiltrated lesions may occur. - Approximately 50% of patients have BRAF mutations.

Question 90

What are the histopathologic findings in Erdheim-Chester disease?

Answer 90

- Tissue samples show xanthomatous or xanthogranulomatous infiltration by lipid-laden or foamy histiocytes, often surrounded by fibrosis. - Bone biopsies reveal infiltration of lipid-laden macrophages, multinucleated giant cells, inflammatory infiltrates of lymphocytes, and histiocytes, along with generalized sclerosis of long bones.

Question 91

What is the first-line treatment for Erdheim-Chester disease?

Answer 91

- Interferon-α is the first-line treatment. - Anakinra and infliximab are considered if interferon-α fails. - BRAF inhibitors have shown efficiency in all treated cases.

Question 92

What are the clinical features of Necrobiotic Xanthogranuloma?

Answer 92

- Multisystem disease affecting older adults, manifesting as yellowish plaques and nodules that can ulcerate. - Predominantly located on the trunk, extremities, and face (periorbital lesions). - Extracutaneous involvement may include eyes, heart, skeletal muscle, larynx, spleen, and ovaries. - Associated with serum monoclonal gammopathy in 80% of patients.

Question 93

What are the differential diagnoses for Necrobiotic Xanthogranuloma?

Answer 93

- Differential diagnoses include: - Necrobiosis lipoidica - Subcutaneous granuloma annulare - Noduli rheumatica - In cases with modest necrobiosis, consider xanthoma associated with paraproteinemia and lymphomas. - Xanthelasma can be a differential diagnosis for periorbital skin lesions.

Question 94

What is the prognosis for Necrobiotic Xanthogranuloma?

Answer 94

- The prognosis is poor, with treatments showing variable results. - Neither treatment nor nontreatment of monoclonal gammopathy influences skin disease activity. - No randomized controlled trials exist for long-term outcomes.

Question 95

What are the clinical features of Hereditary Progressive Mucinosis Histiocytosis?

Answer 95

- Rare, potentially autosomal dominant inherited disease. - Progressive eruptions of self-resolving skin-colored to red-brown papules develop in the first decade on the nose, hands, forearms, and thighs. - Lesions can evolve into persistent and progressive erythematous papules. - Visceral involvement has not yet been reported.

Question 96

What is the first-line treatment for Erdheim-Chester Disease with bilateral and symmetrical long bone involvement?

Answer 96

The first-line treatment for Erdheim-Chester Disease is Interferon-α.

Question 97

What is the prognosis for a patient with Necrobiotic Xanthogranuloma presenting with periorbital lesions and serum monoclonal gammopathy?

Answer 97

The prognosis is poor, and there is an increased risk for concomitant hematologic and lymphoproliferative malignancies.

Question 98

What systemic association should be investigated in a patient with Necrobiotic Xanthogranuloma and ulcerated yellowish plaques?

Answer 98

Serum monoclonal gammopathy, usually of immunoglobulin G κ and λ type, should be investigated.

Question 99

What is the recommended treatment for Erdheim-Chester Disease with retro-orbital tissue involvement?

Answer 99

BRAF inhibitors have been shown to be efficient in cases with retro-orbital tissue involvement.

Question 100

What histopathologic findings are associated with LCH lesions?

Answer 100

LCH lesions show collections of epithelioid S100B/CD1a− and CD68, weak stabilin-1+ histiocytes, and telangiectatic vessels in the upper dermis. In the mid-dermis, nodular aggregates of tightly packed spindle-shaped cells are present, with moderate to extensive mucin production in epithelioid histiocytes and spindle-shaped cells.

Question 101

What are the clinical features of Progressive Nodular Histiocytosis?

Answer 101

Progressive Nodular Histiocytosis is characterized by: 1. Generalized, discrete yellow to red-brown papules and nodules measuring a few centimeters in size. 2. Prominent facial involvement. 3. No involvement of other organs, but there is an association with chronic myeloid leukemia and tumors of the hypothalamus.

Question 102

What is the most sensitive staining marker for LCH?

Answer 102

The most sensitive staining marker for LCH is CD207.

Question 103

Which mutation is associated with 60% of LCH cases?

Answer 103

60% of LCH cases are associated with mutations in the MAP2K1.

Question 104

Which of the following is not considered a 'high-risk' organ in LCH?

Answer 104

The lung is not considered a 'high-risk' organ in LCH.

Question 105

What therapeutic option is available for single lesions in LCH?

Answer 105

Ablative laser therapy, such as with a CO2 laser, is a therapeutic option for single lesions in LCH.

Question 106

What is the treatment of choice for a patient with Progressive Nodular Histiocytosis presenting with yellow to red-brown papules and nodules on the face?

Answer 106

Surgical ablation with a CO2 laser is a therapeutic option.