JPC SYSTEMIC PATHOLOGY

INTEGUMENTARY SYSTEM

October 2022

I-N34 

Signalment (V04-14822):  Tissue from a cat

 

HISTORY:  None 

 

HISTOPATHOLOGIC DESCRIPTION:  Haired skin and bone (1^st and 2^nd phalanges), digit, longitudinal section: Expanding the dermis, elevating the overlying epidermis, and compressing the distal aspect of bone of the 2^nd phalanx is an unencapsulated, poorly demarcated, moderately cellular neoplasm composed of columnar to cuboidal epithelial cells arranged in nests and acini on a dense desmoplastic stroma. Neoplastic cells are lined by apical cilia and have distinct cell borders, a moderate amount of eosinophilic, granular cytoplasm, and a round to oval, basally located nucleus with finely stippled chromatin and one to two distinct nucleoli. There is marked anisocytosis and anisokaryosis, mitotic count is 4 per 2.37 mm², and there is multifocal single cell necrosis. Within the superficial dermis and neoplastic stroma are many lymphocytes, plasma cells, neutrophils, and focally extensive areas of hemorrhage, fibrin, and edema. Subjacent to the epidermis there are increased numbers of small caliber vessels arranged perpendicular to reactive fibroblasts (granulation tissue). The overlying epidermis is moderately hyperplastic with acanthosis and anastomosing rete ridge formation, spongiosis, occasional intracellular edema, and mild orthokeratotic hyperkeratosis. 

 

MORPHOLOGIC DIAGNOSIS:  Haired skin and bone, digit:  Metastatic pulmonary adenocarcinoma, feline.

 

DISEASE: Lung-digit syndrome

 

GENERAL DISCUSSION:  

• Cutaneous metastasis of internal tumors is rare in cats and may be the first sign of an undiagnosed visceral malignancy; pulmonary adenocarcinoma is the most common cause of tumor metastasis to the skin in cats; others are mammary adenocarcinoma (to ventral abdominal tissues) and digestive carcinoma
• Primary pulmonary carcinomas (FPC)
  1. Average age is 12-13 years, senior cats >10 years old predisposed; Persians appear predisposed 
  2. 80% of cases have intra- and extrathoracic metastasis; prognosis is poor
• “Feline lung-digit syndrome (FLD)”, or the newly proposed “feline muscle/ocular/digit/aorta/lung (MODAL) syndrome” describe common locations of pulmonary carcinoma metastasis
• Many malignant epithelial neoplasms are classified by the term pulmonary adenocarcinomas and further divided based on histologic pattern as lepidic, papillary, acinar, squamous, and adenosquamous 
• Cats with moderately differentiated neoplasm have significantly longer survival time (median, 698 days) than cats with poorly differentiated neoplasms (median, 75 days)

 

PATHOGENESIS: 

• Cutaneous metastatic carcinomas
  1. Primary carcinomas metastasize via hematogenous or lymphatic routes; implantation via biopsy may occur
  2. High blood flow to the digits accounts for the digital metastatic location
• Pulmonary Carcinoma
  1. Pulmonary carcinoma in animals commonly arise from Club cells or type II pneumocytes of the bronchioloalveolar region; humans are mainly bronchogenic
  2. Tumors arising from bronchioloalveolar region often have numerous peripheral metastese in lung parenchyma
  3. Tumors located in the hilus generally arise from major bronchi and tend to be a solitary large mass with occasional small metastasis in periphery 

 

TYPICAL CLINICAL FINDINGS:  

• Metastasis usually occurs prior to the onset of clinical signs from the primary neoplasm
• Lameness with minimal to absent pulmonary signs
• Radiographs of the digit reveals bony lysis of the phalanx
• Thoracic radiographs classically reveal a single, large, circumscribed mass in the caudal left lung field

 

TYPICAL GROSS FINDINGS:  

• Lung
  1. Invasive or expansive, variable color (white, tan, or gray), soft or firm, and may have areas of necrosis with a “craterous” or “umbilicate” appearance) 
• Skin
  1. Lesions are suggestive of paronychia (inflammation of the skin that surrounds a nail)
  2. May have lesions on multiple digits, dewclaw is excluded
  3. Swelling, skin ulceration, purulent discharge may be present

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:  

• Nests, solid sheets, and glandular structures composed of malignant epithelial cells in the dermis and subcutis
• Neoplastic respiratory cells have abundant eosinophilic cytoplasm, basally oriented nuclei, and frequent apical cilia
• Squamous differentiation is common
• Desmoplasia is usually present
• Bony lysis of the third phalanx; may also be evident radiographically 

 

ADDITIONAL DIAGNOSTIC TESTS:  

• Cytopathologic features resemble specimens from the primary sites with cilia; may be more anaplastic 
• Histochemical stains: Neoplastic cells often contain and secrete mucin (PAS positive), whereas primary adenocarcinomas of the digit would be PAS negative
• Immunohistochemistry: Positive immunoreactivity for pancytokeratin and variable immunoreactivity for thyroid transcription factor-I and poor immunoreactivity for vimentin 

 

DIFFERENTIAL DIAGNOSIS:

Gross:

• Squamous cell carcinoma is most common digit tumor followed by fibrosarcoma 
• Causes of paronychia: Bacterial and fungal infection, immune mediated disease

Histologic: 

• Primary cutaneous apocrine or eccrine carcinoma: epithelium is not ciliated; TTF-1 negative; PAS negative
  1. Eccrine carcinomas are rare
  2. Bony invasion by an apocrine adenocarcinoma is unlikely

 

COMPARATIVE PATHOLOGY:  

Cutaneous metastasis of visceral neoplasia:

• Dogs: 
  1. Urothelial (transitional cell) carcinoma (U-N04):  Cutaneous metastasis has been reported after abdominal surgery; most cases of cutaneous lesions are plaques, papules, and nodules close to the vulva or prepuce, possible that urine may seed the neoplastic cells to scalded skin 
  2. Visceral hemangiosarcomas (C-N02) may metastasize to the subcutis; a subcutaneous location of hemangiosarcoma suggests a primary visceral tumor
  3. Mammary gland carcinomas: may metastasize to the dermis of the inner thigh
  4. Other reported cutaneous metastases:  mast cell tumors, lymphoma, duodenal and colonic adenocarcinoma, gastric mucinous adenocarcinoma, inflammatory mammary carcinosarcoma, seminoma, osteosarcoma, nasal neuroendocrine carcinoma, rhabdomyosarcoma
• Llama: Report of cutaneous metastasis of mammary adenocarcinoma 

 

REFERENCES:  

1. Caswell JL, Williams KJ: Respiratory system. In: Maxie MG ed. Jubb, Kennedy, and Palmer's Pathology of Domestic Animals. Vol 2, 6th ed. Philadelphia, PA: Elsevier Saunders; 2016:495-500.

2. Mauldin EA, Peters-Kennedy J.  Integumentary system.  In: Maxie MG, ed. Jubb, Kennedy and Palmer’s Pathology of Domestic Animals. Vol 1. 6th ed. Philadelphia, PA: Elsevier Ltd; 2016:736.

3. Raskin RE, Conrado FO. Integumentary System. In: Raskin RE, Meyer DJ, Boes KM eds. Canine and Feline Cytology. 4th ed. St. Louis, MO: Elsevier; 2023:82-83.

4. Santos, IR, Raiter J, Lamego EC, et al. Feline pulmonary carcinoma: Gross, histologic, metastatic, and immunohistochemical aspects [published online ahead of print September 13 2022]. Vet Pathol. 2022. 

https://doi.org/10.1177/03009858221122. Accessed October 12, 2022.

 

 

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