Cutaneous Histiocytosis (B)
Dr. Naguman PGR
Dermatology
Non-Langerhans Cell Histiocytosis
These are group of rare disorder characterized by accumulation
and proliferation of histiocytes.
Lack phenotypic features of langerhans cell histiocytosis.
including
. CD1a negativity
. Langerin (CD207) negativity
. Absence of berbick granules on electron microscopy.
Disorder with mainly skin involvement
with/without a systemic component
Juvenile xanthogranuloma
Most common non-LCH disorder.
Benign proliferative disorder of histiocytes.
Occurs in early infancy and childhood with spontaneous
regression In most cases.
Associated with neurofibromatosis type 1 (NF1) and juvenile
myelomonocytic leukaemia (JMML) .
Histopathology;
Dense dermal infiltrate of small histiocytes.
Which are positive for factor XIIIa, CD68,
CD163 and CD14 and stain negative for S100
and CD1a.
Touton giant cells are present in 85% of cases.
Which are wreath-like nucleus around
eosinophilic centre with foamy cytoplasm at
periphery .
Clinical features;
Cutaneous lesions are most common
Initially reddish-yellow macules or papules which progress to become
yellow-brown plaques with surface telangiectasia
On face, head, neck followed by upper torso, arms and legs
Extracutanous presentation occurs in eyes,(most common), liver,
spleen, lung and CNS.
Ocular complications are hyphema, glaucoma and blindness.
Fatalities have been reported in progressive CNS and hepatic
involvement.
Management.
Usually do not require treatment as these resolve spontaneously.
Surgical excision may be done for single accessible lesions
Ocular lesions are treated with topical, intralesional and
subconjunctival corticosteroids.
In systemic disease, LCH-based agent (Vinblastine, prednisolone
and methotrexate) commonly used.
Life-threatening and progressive disease are treated with multi-
agent chemotherapy (Cytarabine, Vincristine, methotrexate and
prednisolone).
Benign cephalic histiocytosis
Considered as a mild or localized variant of JXG without systemic
involvement.
Asymptomatic, red to brown macule, papule, nodules which
particularly occurs over the face.
Extension onto the trunk, upper limb and rarely buttock may be
seen.
There is no mucosal involvement
Self-limiting .
Generalized eruptive histiocytosis
This is a rare cutaneous histiocytosis that mainly effects adult.
The disease present with multiple, symmetrical red-brown papules
on face, trunk and arms
Flexures typically spared
Histology shows proliferation of monomorphic histiocytic cells in
upper and mid dermis, no giant cells or foam cells are present
The disease generally self-limiting, doesn’t requires treatment.
Treatment options includes PUVA, thalidomide, chloroquine and
steroids
Papular xanthoma
This is a rare histiocytic disorder that was first described in adults and
subsequently reported in children
Resembles with JXG or xanthoma disseminatum but with distinct features
Characterized by yellow or reddish-yellow papule or plaques(2-12mm) with
both skin and mucous membranes involvement.
In adults: mucosa involvement and potential progression.
In children: Spontaneous resolution in 1 to 5 years.
Management;
. No treatment required in children
. No proven therapy is effective in adults.
Progressive nodular histiocytosis
Consist of two different types of lesions.
Superficial papules: (2 to 10 mm) yellow-orange in colour.
Deep nodules: (1 to 5 cm) reddish-orange or skin-coloured.
Which can be hundreds in number.
Lesion may occurs in mucosa.
About 50% of patients are complicated with diabetes insipidus.
Management:
. No proven treatment
. Surgery for large/painful lesions
. Limited response to chemo/radiation in early disease
Xanthoma disseminatum
This is a rare non-familial disease, characterized by
proliferation of histiocytic cells with secondary lipid
deposition.
Associated with diabetes insipidus in 40% of cases.
Histopathology: There is dermal infiltrate of foamy
histiocytes, touton giant cells, lymphocytes and
eosinophils.
Clinical features
Symmetric, Erythematous, yellow brown papules and nodules, on
the trunk, scalp, and proximal extremities
The lesions become confluent, especially in flexures.
Form xanthomatous plaques, which may become verrucous.
Mucosal involvement in 40 to 60%
. lips, pharynx, larynx, conjunctiva, bronchus
Upper respiratory tract: risk of stridor, airway compromise
CNS: meningeal infiltration, seizure and intracranial mass-like
lesions.
Disorders in which skin may be involved but
systemic component predominates
Erdheim-Chester disease
This is a rare lipoid granulomatosis characterized by infiltration
of viscera, bones, retroperitoneum and skin
The age range was 7-84 years
Skin involvement is seen in about 20% of patients, usually
presenting with xanthoma like lesions, usually on the eyelids
but occasionally on the trunk and sub mammary area
The most common presentation is with chronic mild bone pain
Bilateral long bone involvement is hallmark
Other organ involved are lungs, heart, and CNS.
Histological examination shows a xanthogranulomatous infiltration
by lipid-laden histiocytes within a mesh and surrounded by fibrosis.
Touton giant cells and eosinophils may be prominent.
Prognosis tends to be poor despite treatment.
Overall mortality is around 60%.
Management;
Active treatment is typically reserved for symptomatic patients
A variety of therapeutic options are available. These include surgical
debulking, high-dose corticosteroids, ciclosporin, interferon a,
systemic chemotherapy and radiation therapy.
The commonest chemotherapy drugs utilized have been vinca
alkaloids, anthracyclines and cyclophosphamide
Disorder with mainly skin involvement with or
without a systemic component
Reticulohistiocytoma
It is the localized variant of multicentric reticulohistiocytosis
This uncommon tumour is generally solitary and asymptomatic
Lesions are less than 1 cm in diameter and present as papules or
dome-shaped nodules.
They may occur anywhere on the body including the genitalia.
Treatment;
. surgical excision showed no recurrence following primary
excision
Familial sea-blue histiocytosis
A rare inherited disorder of lipid metabolism characterized by the
presence of “sea-blue” histiocytes in bone marrow and other tissues.
Named for the deep azure blue cytoplasmic granules seen with
May-Gruenwald stain.
Characterized by patchy grey-brown pigmentation, subcutaneous
nodules (face, chest, shoulders)
Hepatosplenomegaly and thrombocytopenia are common.
There is no specific treatment available for sea-blue histiocytosis.
Malakoplakia
It is an immunodeficiency disorder where macrophages fail to
phagocytose and digest bacteria properly.
The term ‘malakoplakia’ means soft plaque.
Most commonly affects the urinary and gastrointestinal tracts.
Cutaneous lesions are rare and non-specific
Includes draining abscesses, sinuses, ulcers, fluctuant masses,
isolated tender nodules and grouped papules have been reported.
Histology sheets of large histiocytic cells with abundant
cytoplasm are present in the skin, affecting any level from
epidermis to subcutaneous fat.
The cells have fine eosinophilic granules in their cytoplasm and
are referred to as Hansemann cells.
They contain one or more round basophilic inclusion bodies
( Michaelis-Gutmann bodies ).
Which are considered pathognomonic for the disease and
are thought to represent abnormal degradation of bacteria.
The commonest bacterium found in this disease is
E.coli, Staphylococcus aureus and mycobacteria have
also been identified.
Management includes surgical excision.
Antibiotics for the associated infections, in which
quinolones seem to be superior.
Necrobiotic xanthogranuloma
It is a multisystem histiocytic disease which is strongly associated
with haematological malignant conditions.
Approximately 80-90 % of patients have an underlying monoclonal
gammopathy
The characteristic clinical lesions are subcutaneous nodules and
xanthomatous plaques with atrophy and ulceration
Often periorbital, but may occurs on trunk and limbs
Systemic symptoms have been reported, including nausea,
vomiting, epistaxis, back pain and Raynaud’s phenomenon.
Management;
Therapy aimed at underlying gammopathy.
Includes alkylating agent such as melphalane with or without
prednisolone has resulted temporary clearing of the skin.
Other therapy includes, Intralesional corticosteroids, high-dose
systemic steroids, cyclophosphamide and methotrexate.
Plasmapheresis reduced the level of the circulating monoclonal
IgG.
Disorders in which skin may be involved but the
systemic components predominates
Multicentric reticulohistiocytosis
This is a multisystemic disorder characterized by cutaneous and mucosal
involvement with destructive arthropathy.
Cutaneous lesions are firm brown or yellow papules and plaques
particularly on extensor surfaces of hands and forearms.
Mucosal involvement of lips, tongue and pharynx are common.
2/3rd of patients present with symmetrical polyarthritis typically affects
the hands, but other joints may be involved.
20% of cases are associated with internal malignancy.
Around 15% of cases have been associated with autoimmune
disease (SLE, Diabetes and Sjögren)
Management;
. Treatment of underlying disease is important.
. Methotrexate alone or with combination may be effective.
.Successful therapy with bisphosphonates has been reported.
. Other effective agents includes, cyclophosphamide,
azathioprine, ciclosporin and prednisolone.
Sinus histiocytosis with massive
lymphadenopathy
Also known as Rosai-Dorfman disease.
Characterized by abundant histiocytes in lymph nodes throughout the
body
Present with massive bilateral cervical lymphadenopathy.
With fever, malaise, night sweats and leucocytosis.
Extranodal involvement in 43% mainly over skin.
Skin lesions are usually red papule, nodules or infiltrated plaques often
with telangiectasia and scaling.
Histology;
Massive sinus infiltration by
large histiocytes.
Emperipolesis (Intact
lymphocytes with in
histiocytes)
Management;
Usually is self-limiting but
can relapse.
Surgical excision is
effective for isolated cases.
Systemic corticosteroids
reduces size and relieves
symptoms but regrowth is
common.
Malignant Histiocytoses
Malignant reticulohistiocytosis
Neoplastic proliferation of histiocytic cells typically involves liver,
spleen, lymph nodes and bone marrow.
Present with fever, sweats, painful lymphadenopathy and
hepatosplenomegaly.
Skin is involved in 10-15% of cases, with skin-coloured to
violaceous papulonodular lesion, often on lower legs or buttock,
may ulcerate.
Vascular invasion leads poor prognosis.
Treatment with early chemotherapy and radiotherapy is
essential.
Bone marrow transplant is effective in post relapse.
True histiocytic lymphoma
This is a localised tumour of malignant histiocytes that may disseminate.
May be nodal or extranodal.
Presents with painless lymphadenopathy.
Can involves bone and GIT.
Skin lesions are localised bluish-red tumour, can grow very large.
Management;
No recent advances in therapy.
Electron beam therapy effective for localised skin lesions.
Histiocytic sarcoma
It is an extremely rare, aggressive non-LCH disorder of unknown
cause.
Present with unifocal or multifocal extranodal tumours.
Most often in intestinal tract, skin, soft tissue, bone marrow and
spleen.
Skin involvement is seen in children with multiple isolated lesions,
which are mmaculopapular rash, or subcutaneous nodules with
central necrosis & ulcers
Aggressive course, poor response to standard therapies.
Surgery or radiotherapy for localised skin lesions.
Thank You
A 30-year-old male has painless bilateral cervical
lymphadenopathy. Histology shows dilated sinuses filled
with large histiocytes engulfing intact lymphocytes
(emperipolesis). Which is the correct diagnosis?
A. Multicentric Castleman Disease
B. Hodgkin Lymphoma
C. Rosai-Dorfman Disease
D. Erdheim-Chester Disease
A dermal biopsy from a cutaneous lesion in a toddler
shows a dense infiltrate of histiocytes, multinucleated
giant cells with a wreath of nuclei and peripheral foamy
cytoplasm, and an absence of CD1a and CD207 on
immunostaining. Which of the following is the most
specific histological feature supporting Juvenile
Xanthogranuloma?
A. Emperipolesis
B. Birbeck granules
C. Touton giant cells
D. Atypical mitotic figures
