Cutaneous histiocytoma

Langerhans cell histiocytosis

Reactive histiocytosis (cutaneous and systemic)

Histiocytic sarcoma (localized and disseminated) AKA malignant histiocytosis

Canine cutaneous histiocytoma is a common, benign cutaneous neoplasm that originates from Langerhans cells and will regress spontaneously, usually in 1-2 months

Approximately 50% of Langerhans cell histiocytosis will regress. Those with LN involvement will NOT regress.

Dogs < 3 years old

Occasionally develops in older dogs

Langerhans cell histiocytosis

Develops as multiple cutaneous histiocytomas at the same or distant sites with possible involvement of internal organs and LNs

Cutaneous lesions (can be hundreds) ranging from nodules to masses that elevate the epidermis (erythematous papules, plaques and crusts)

Alopecia, erythema and ulceration can be common

Lesions at mucocutaneous junctions and in tissues of the oral cavity may also occur. Lesions may be initially limited to skin or involve skin and draining lymph nodes. Rarely, internal organ involvement also occurs.

Lesions will be dominated by activated dermal interstitial DCs and T cells that frequently infiltrate the walls of dermal vessels

Lesions generally arise form the deep dermis and thus have a "bottom-heavy" topography rather than the "top-heavy" topography of histiocytomas

No

But...multiple histiocytomas may develop more often in Shar Pei dogs (they accounts for ~20% of the cases)

Excision of the lesions (if possible)

Immunosuppressive (prednisolone has not been associated with good outcomes) and immunomodulatory (griseofulvin, cyclosporin) medications

Chemotherapy

Others: Cryosurgery, electrosurgery and "benign" neglect

Lymphocytes

These lymphocytes likely mediate lysis of neoplastic histiocytes, since it has been shown that the tumor-infiltrating lymphocytes are highly enriched for CD8+ T cells (cytotoxic cells capable of mediating regression)

CD1a

CD11a/CD18

CD11c/CD18

CD44

CD45,

MHC class II

E-cadherin (expression may be limited to the histiocytic

infiltrate immediately adjacent to the epidermis)

Tumor histiocytes variably express:

CD11b/CD18 and CD54.

Tumor histiocytes do not express:

CD90 (Thy-1) and CD45RA

Since DCs (cell line of origin) are so ubiquitous, HS can arise in nearly every tissue.

Lesions may be solitary or multiple. Histiocytic sarcomas

may be localized—that is, they originate at a single tissue site or in a single organ (with solitary or multiple foci). Once the lesions spread beyond the local draining lymph node to involve distant sites, the disease is then considered disseminated HS.

Localized and disseminated HS have been observed in cats at a far lower incidence than in dogs.

Bernese Mountain Dogs have a familial predisposition but other breeds including Rottweilers, goldens and flat coated retrievers may also be predisposed.

Primary lesions of HS occur in spleen, lymph node, lung, bone marrow, CNS, skin and subcutis, and periarticular and articular tissues of the limbs.

Clinical signs of HS = vague (anorexia, weight loss, lethargy, other signs depend on the organs involved

and are a consequence of destructive mass formation).

A middle-aged to older cat (7-17 yrs) with a solitary skin nodule or more commonly multiple papules, nodules, or plaques measuring up to 1.5 cm in diameter on the head lower extremities or trunk.

The nodules are firm, nonpruritic, and nonpainful. The surface is often alopecic and may be ulcerated.

No.

The lesions may wax and wane though.

Feline progressive histiocytosis behaves as a low-grade HS but...

a proportion of cats develop invasive, expansile masses in lymph nodes and internal organs, including the lungs, kidneys, spleen, and liver.

Feline progressive histiocytosis has a poor long-term prognosis, since the wide variety of treatments used have lacked efficacy.

No...to date this disease has only been described in dogs.

Reactive histiocytoses are either confined to skin and draining lymph nodes (CH) or involve skin and extracutaneous sites (SH).

CH is more common than SH.

The clinical course in both diseases is marked by remissions

and relapses, particularly early in the course.

The lesions of CH and SH may wax and wane, and spontaneous resolution without therapy occurs. This makes it difficult to assess the effects of therapy.

Seemingly effective therapies used to date = prednisolone, cyclosporine, leflunomide, tracycline/niacinimide

Cutaneous histiocytosis is an inflammatory lymphohistiocytic proliferative disorder that primarily involves skin (face, nose, neck, trunk, extremities (including foot pads), perineum, and scrotum) and subcutis

Lesions most often occur as multiple cutaneous and

subcutaneous nodules up to 4 cm in diameter; solitary lesions are uncommon.

Overlying skin ulceration is common.

Systemic histiocytosis was originally described in related Bernese Mountain Dogs but has been observed in other breeds less commonly (Rottweiler, Lab, Basset Hound, Irish

Wolfhound)

A young to middle-aged dog (2-8) with multiple cutaneous

nodules distributed over the entire body but especially

on the scrotum, nasal apex, nasal planum, and

eyelids.

Ulceration of the skin overlying the nodules is common. Peripheral lymph nodes may be palpably enlarged by the histiocytic infiltrates

Lesions may only be fully appreciated at necropsy... :(

-Most common histiocytic disease in cats

-Begins as cutaneous nodules and plaques

-Poor long term prognosis

-Behaves as low-grade HS with indolent behavior initially

-Disease of aged cats

-Progressive respiratory failure, obliteration of pulmonary parenchyma by LC infiltrate

1) Feline progressive histiocytosis (FPH)

2) Pulmonary Langerhans cell histiocytosis

-More common in dogs than cats

-Localized lesions in the spleen, LNs, lung, BM, skin, subcutis, brain, articular tissue

-Disseminated HS (previously malignant histiocytosis)

-may occur as multiple lesions in single organs (esp. spleen and skin) and rapidly disseminate to involve multiple organs

-Mostly arise from interstitial DCs

-Hemophagocytic form of HS is distinct entity that arises from splenic red pulp +/- BM macrophages

-only identified in dogs

-Cutaneous histiocytosis

-Systemic histiocytosis

-Related disorders arising from activated interstitial DCs

-Histiocyte and lymphocyte rich inflammatory disorders associated with immune dysregulation

-Canine cutaneous histiocytoma (LC differentiation, solitary lesion in young dogs and exhibits spontaneous regression)

-Cutaneous Langerhans cell histiocytosis (LCH)

Multiple cutaneous lesions observed, LN and systemic metastasis observed sometimes and individual skin lesions may resemble histiocytoma

-Canine cutaneous histiocytoma +LCH could be considered part of a larger spectrum of diseases with diverse biological behavior

-No feline counterparts were identified

-Mutation chromosome 5 (Birt-Hogg-Dube locus in humans)

-Associated: renal cystadenomas/adenocarcinoma, Uterine leiomyoma/sarcoma

-Multiple collagenous nodules

-No association with UV light exposure!

-Dogs: location is important

• ---> Melanomas (oral: malignant; lip: aggressive; nail bed (black dogs): malignant---> metastasis to LN---> lungs---> other organs
• --->Melanocytomas: trunk, proximal legs

-Cats: rare

-MHC II

-CD11c

-E-cadherin

-Claudin-1

*Typical-spontaneous regression

-Dogs >> cats

-Solitary, occasionally multiple

-Amyloid deposited

-Morphology: hyaline; mature, cleaved, asynchronous, polymorphous-blastic

-limited prognostic value

-CD18+/-, CD45RA, CD79a (80%), MUM-1 (multiple myeloma antigen)

-Solitary, multiple skin nodules/plaques

-No pruritus

-Predilection sites: legs, feet, face

-Other locations

-Progressive skin lesions

-Histiocytic sarcoma

-Progression to internal disease

-Stains: CD18, MHCII, CD204 and CD1

• Multiple histiocytomas
• +/- T cell infiltration
• +/- Lymph node involvement