D.N. Carlotti, DECVD
1. Pseudo-neoplasms: two definitions exist for this term :
a. non-neoplastic tumours i.e., lesions caused by an abnormal development of any cutaneous or subcutaneous structure, for unknown cause. This refers to aetiology and pathogenesis and includes cysts, nevi, and keratoses.
b. all non-neoplastic lesions which are clinically nodules, tumours or plaques. This is a wider definition which includes the above-mentioned lesions and others. It is preferable. In addition, all these lesions can be ulcerated. Pseudo-neoplasm is a better term than pseudotumour.
2. Non-neoplastic nodules: nodules are circumscribed solid elevations, larger than 1 cm which generally extend into the hypodermis. Non-neoplastic nodules are caused by massive infiltration of inflammatory cells, or more rarely by deposition of fibrin or crystalline material.
3. Nodular dermatitis: this is a histopathological term meaning dermal infiltration in clusters, solitary or more often multiple.
4. Plaques: plaques are large flat topped elevation formed by the extension or papules.
5. Ulcers: an ulcer is a loss of epidermal and dermal tissues, exposing the underlying dermis. An ulcer is always an indication for severe pathologic process.
6. Granuloma: this is a histopathological term meaning circumscribed tissue reaction characterized by an organized infiltration of mononucleated phagocytes (histiocytes or macrophages). A granulomatous reaction may be nodular or diffuse and may occur when foreign bodies, bacteria, fungi, parasites, or any material penetrate the skin. If the "invader" is not destroyed by an acute inflammatory process, macrophages become "epithelioid". A granuloma may persist until the cause has been destroyed.
7. Pyogranuloma: this is a histopathological term meaning granulomatous reaction with any neutrophils.
Granulomas and pyogranulomas
1. Aetiology: Granulomas and pyogranulomas can have many causes or may be idiopathic.
a. Bacterial granulomas and pyogranulomas
i. Canine bacterial furunculosis may have a nodular aspect. Pyogranulomatous reaction occurs around hair fragments, keratine debris and Cocci.
ii. Botryomycosis (bacterial pseudomycetoma): various bacteria may cause a granulomatous reaction surrounding "grains" (Staphylococcus sp., Pseudomonas sp., Proteus sp., Streptococcus sp., Actinobacillus sp.). Lesions are often caused by trauma (bites) or foreign bodies.
iii. Nocardiosis (actinomycotic mycetoma caused by Nocardia sp.)
iv. Mycobacteriosis: cutaneous tuberculosis has now disappeared at least in Europe and North America (Mycobacterium tuberculosis, Mycobacterium bovis, Mycobacterium avium). Atypical mycobacteria, which are opportunistic, can rarely generate pseudo-neoplastic lesions. Feline leprosy caused by Mycobacterium sp. (including lepraemurium) is seen in certain parts of the world.
b. Fungal granulomas and pyogranulomas
i. Dermatophytosis: kerions are nodular lesions caused by dermatophytes. In cats, pseudomycetoma caused by dermatophytes have been reported.
ii. Sub-cutaneous (intermediate) mycosis: sporotrichosis (Sporothrix schenchkii), pythiosis (Pythium sp.), mycetomas (Curvalaria, Petriellidium, Exophilia, Madurella sp. "grains" come out from fistulae), phaeohyphomycosis (Dreschslera, Exophiala, Cladosporium, Phialophora sp.), zygomycosis.
iii. Deep (systemic) mycosis: blastomycosis (Blastomyces dermatitidis), coccidioidomycosis (Coccidioides immitis), histoplasmosis (Histoplasma capsulatum), aspergillosis (Aspergillus sp.), cryptococcosis (Cryptococcus neoformans), particularly seen in FeLV of FIV infected cats, protothecosis (Prototheca sp.), paecilomycosis, trichosporonosis.
c. Foreign bodies granulomas: foreign bodies granulomas can lead to nodular lesions, with endogenous and exogenous causes.
i. Endogenous causes:
a) hair and keratine: bacterial furunculosis
b) calcium: calcinosis can be seen in :
(1) calcinosis circumscripta: pink-coloured nodules or plaques located on pressure points or in the tong containing crayish material.
(2) calcinosis cutis: this is a lesion seen in spontaneously occurring or iatrogenic Cushing's disease. Granulomatous reaction is frequently seen.
ii. lipids: xanthomas are seen in case of diabetes mellitus with hypertriglyceridemia in the dog and in the cat. Cases have been described in cats with hereditary hyperlipoproteinemia. Granulomatous reaction is frequent, with foamy macrophages
iii. Exogenous causes:
a) sutures (with true granulomatous reaction)
b) vegetal foreign bodies (grass awns, thorns...), with granulomatous or pyogranulomatous reactions.
d. Parasitic granulomas
i. canine localized demodicosis: nodular forms have been described (tail, feet) particularly in Shar Peis
ii. tick bites (Dermacentor, Rhipicephalus, Ixodes sp.). Erythematous nodules can be seen.
iii. other arthropod bites, including sterile eosinophilic furunculosis
iv. canine filariasis (Dirofilaria immitis): this is a rare cause of nodular dermatitis in the dog.
v. canine leishmaniasis (Leishmania infantum): the nodular form of the disease is relatively rare. Short-haired breeds such as Boxers are predisposed.
vi. canine dracunculosis (Dracunculus insignis)
vii. cysticercosis (Taenia crassiceps)
viii. feline toxoplasmosis (Toxoplasma gondii) and canine neosporosis (Neospora caninum)
e. Idiopathic granulomas
i. eosinophilic granuloma: In the cat, there are classically three forms of the disease : indolent ulcer, eosinophilic plaque, eosinophilic granuloma, often secondary to cutaneous allergy. The only form which is truly granulomatous is the eosinophilic granuloma, in which flame figures are seen. In the dog, non-pruritic cutaneous or oral nodules occur rarely. Foci of collagen degeneration and/or flame figures are surrounded by a granulomatous reaction, which may be palisading, with many eosinophils.
ii. sterile granuloma and pyogranuloma: this disease is mainly seen in the dog and is clinically characterized by multiple nodules. No infectious agent can be discovered in the more-or-less coalescent pyogranulomas.
iii. granulomatous sebaceous adenitis: nodular forms have been mentioned (on the head).
iv. nodular sterile panniculitis: in dogs and cats deep nodules which fistulize are caused by an inflammatory process of sub-cutaneous fat. Foamy macrophages are numerous.
v. canine cutaneous histiocytosis: multiple nodules and plaques are caused by proliferation of normal histiocytes. They are often located on the face (e g "clown nose").
vi. erythema nodosum-like (very rare).
vii. canine sterile sarcoidal granulomatous skin disease: plaques and nodules have been reported, with histopathological aspects of sarcoidal (epithelioid) deep granulomas.
viii. cutaneous amyloidosis: subcutaneous nodules, particularly on the ear pinnae. Amyloid material is surrounded by lymphocytes, plasma cells and macrophages.
2. Diagnosis: Diagnosis of granuloma and pyogranuloma is based mainly on histopathology. In addition, bacterial and fungal culture may be useful, and appropriate investigation for parasites, foreign bodies and metabolic or immunological diseases as well.
3. Therapy: Therapy is mainly anetiological, i.e., antibacterial, antifungal or antiparasitic. Removal of foreign bodies is indicated. Control of metabolic disorders is helpful (e.g., calcinosis cutis disappears when Cushing's disease is controlled). Idiopathic granulomas respond in many instances to glucocorticoid therapy at immunosuppressive dosage.
Cysts, Nevi and keratoses
1. Cysts: Cysts are non-neoplastic epithelial lesions which contain keratin or a secretion.
a. keratinous cysts
i. epidermoid cysts are acquired lesions (maybe traumatic) containing a grayish cheesy material. An epithelial envelope keratinises as the epidermis; no adnexal structure is seen.
ii. follicular cysts are caused by retention of material (keratin, glandular products) due to congenital or acquired loss or obliteration of follicular orifices. They should be differentiated from pustules and calcinosis cutis. Glands are visible, as well as secondary follicles sometimes.
iii. pilar (trichilemmal, isthmus-catagen) cysts resemble epidermoid and dermoid cysts and are dilated hair follicles containing keratin due to trichilemmal keratinisation. Matrical cysts derive from matrical (inferior) segment of anagen hair follicle. There are also hybrid cysts.
iv. dermoid cysts are hereditary lesions (focal reduplication of the entire skin structure).Epithelial walls contain adnexae.
b. apocrine cysts Apocrine cysts are fluctuant, round, bluish, well circumscribed lesions containing anaqueous liquid. They are often multiple and adjacent in the dog ("apocrine cystomatosis"),each one having a diameter of 0.5 to a few centimeters. They are sometimes called apocrine hamartomas or nevi. In the cat, apocrine cysts are seen on the ear pinnae and in the external ear canal, with an aspect of shots.
c. treatment: cysts should be surgically excised when feasible.
2. Nevi: An hamartoma is a malformation with tumoral aspect, formed by components which are normal parts of the organ in which it develops but which are arranged erroneously (CIVATTE). A nevus is a cutaneous hamartoma which may arise from any skin component. Nevi are rare, congenital or not and the mechanism of their formation is unknown.
a. Collagenous nevi are single or multiple nodules (0.5 to a few cm) with sometimes an "orange peel" appearance. Large nodular areas of collagene hyperplasia characterize the disease histopathologically. In German Shepherds multiple collagenous nevi may appear, particularly on the limbs (leading to lameness), associated with renal adenocarcinomas and uterine leiomyomas. This syndrome, due to an autosomal dominant gene, is called "nodular dermatofibrosis".
b. Organoid or pilo-sebaceous nevi are solitary or multiple lesions, pedunculated or linear, seen on the hand or the limbs. Hyperplasia of hair follicles and sebaceous glands are the main histopathological features (apocrine sweat glands remaining normal). Focal adnexal dysplasia is similar but there is inflammation and a bizarre configuration.
c. Vascular nevi or angioma are often multiple lesions seen in the scrotum but also all over the body surface. Bleeding is frequent. Histopathology shows a cavernous telangiectasia.
d. Sebaceous nevi are very rare congenital lesions characterized by sebaceous hyperplasia involving multiple folliculosebaceous units and papillomatosis. Miniature Schnauzer comedo syndrome can be considered as a pseudoneoplasm.
e. Epidermal nevi are hyperpigmented linear plaques seen on the trunk or limbs, histopathologically characterized by orthokeratotic hyperkeratosis and papillomatosis.
f. Follicular nevi are plaques (several cms in diameter) containing clusters of normal anagen primary hair follicles that are large and extend deeply.
g. Treatment: nevi should be surgically excised when feasible.
3. Keratoses: Keratoses are solid, elevated, circumscribed lesions caused by hyperproduction of keratin.
a. Seborrheic keratoses are idiopathic multiples greasy nodules or plaques. Histopathologically, basaloid or pseudo-malpighian hyperplasia is seen, with hyperkeratosis and papillomatosis.
b. Actinic keratoses are erythemato-squamous or crustosus lesions seen in hypopigmented areas with few hairs, due to excessive exposure to sunlight. Histopathology shows parakeratosis, epidermal dysplasia and dermal solar elastosis. Evolution towards squamous cell carcinoma is frequent.
c. Lichenoid keratoses are idiopathic single erythematous and squamous plaques seen on the ear pinnae. Histopathologically there are hyperkeratosis, epidermal hyperplasia and a subepidermal lichenoid infiltrate.
d. Cutaneous horns are either idiopathic or associated to various skin neoplasms. Consequently, an underlying neoplasm should be considered in all cases. They may be single or multiple, particularly on footpads of cat with FeLV infection. Compact keratin looks laminated and is sometimes parakeratotic.
e. Treatment of keratoses is mainly surgical. Solar eviction is recommended afterwards in actinic keratoses.
1. Acral lick dermatitis is most often a deep bacterial folliculitis with retrograde hidrosadenitis. They may have a nodular or plaque-like aspect.
2. Idiopathic lichenoid dermatitis is a rare skin disorder of unknown cause but probably immune-mediated. Squamous and coalescent papules and plaques are characteristic. Histopathology shows a lymphoplasmacytic interface lichenoid dermatitis.
3. Feline Plasma cell pododermatitis and stomatitis: non-painful swelling of multiple footpads, on more than one paws, with late ulceration is highly suggestive of the pedal disease. Ulcerative, proliferative and symmetrical stomatitis is suggestive of the oral disease. Glomerulonephritis can be associated. Also, association with FeLV and FIV infection is frequent. Histopathology shows perivascular or diffuse plasma cell infiltration with neutrophils in case of secondary bacterial infection. Surgical excision is recommended. Chrysotherapy may be helpful.
4. Poxvirus infection in the cat: papular to nodular and ulcerative lesions can be seen. There is hydropic degeneration of keratinocytes and intracytoplasmic eosinophilic inclusion bodies.
5. Cheloids (fibrous tissue)
6. Skin tags (due to trauma)
7. Mucinosis can be secondary (e.g., hypothyroidism, acromegaly, SLE, mycosis fungoides).It is physiological in Shar Peis. Idiopathic focal cutaneous mucinosis is a rare nodular disease described in Dobermans.
Nodules, tumours and plaques are not necessarily neoplasms. Diagnosis of pseudoneoplasms is based on clinical aspects and diagnostic tests, particularly histopathology. Specific treatment is often possible.
References are available upon request.