JPC SYSTEMIC PATHOLOGY

SPECIAL SENSES SYSTEM

April 2024

S-N05 (NP)

 

Signalment (JPC #844012): Cat

 

HISTORY: Tissue from a cat with exophthalmos because of progressive retrobulbar swelling beginning in the zygomatic arch.

 

HISTOPATHOLOGIC DESCRIPTION: Lacrimal gland, conjunctiva, and retrobulbar skeletal muscle: Expanding the lacrimal gland, infiltrating the conjunctival subepithelial connective tissue, and extending to the cut border is an unencapsulated, densely cellular, multilobular neoplasm composed of polygonal cells arranged in cords, tubulopapillary projections, and acini on a prominent basement membrane. Neoplastic cells frequently palisade along a moderate fibrovascular stroma subdivided by narrow bands of dense fibrous connective tissue. Individual neoplastic cells have variably distinct cell borders, a moderate amount of finely vacuolated to eosinophilic, granular cytoplasm, and one irregularly round to oval, often basally located nucleus with finely stippled chromatin and 1-2 nucleoli. There is mild anisokaryosis and anisocytosis. The mitotic count is 1-2 per 2.37mm². Multifocally, the surrounding fibroadipose tissue and ocular muscle are expanded by edema, hemorrhage, and few lymphocytes and plasma cells. 

 

MORPHOLOGIC DIAGNOSIS: Lacrimal gland, conjunctiva, and retrobulbar skeletal muscle: Lacrimal gland adenocarcinoma, breed unspecified, feline.

 

GENERAL DISCUSSION: 

• Orbital tumors may be primary to the orbit, occur as a result of local extension from an adjacent structure (such as the salivary gland), or develop subsequent to hematogenous dissemination
• Lacrimal gland tumors can affect either the nictitans or the main lacrimal gland
• Primary tumors predominate in dogs; secondary tumors are more common in cats
  1. Lacrimal gland adenocarcinoma is the most common primary orbital epithelial neoplasm in dogs (although infrequent); it is locally invasive, often recurs after excision, but metastases are not reported
  2. Adenomas occur, but are less common
• Lacrimal glands: 
  1. Compound tubuloalveolar or tubuloacinar; serous to mucous proportion varies with species
  2. Cats have serous glands; dogs have mixed glands
  3. Located in the dorsolateral quadrant of the orbit posterior to the sclera and adjacent to the third eyelid

• According to a recent study, the most commonly diagnosed lacrimal gland tumors in dogs were pleomorphic carcinoma and ductal carcinoma, followed by epithelial-myoepithelial carcinoma and adenoid cystic carcinoma (Giudice, 2021, Vet Pathol)
• The most commonly diagnosed feline lacrimal gland tumor was adenocarcinoma NOS (not otherwise specified) (Giudice, 2021, Vet Pathol)

 

TYPICAL CLINICAL/GROSS FINDINGS:  

• Pink, lobulated mass in the dorsolateral quadrant of the orbit 
• Unilateral proptosis
• Deviation of the globe
• Transient epiphora
• Secondary keratoconjunctivitis, corneal ulceration, retinal detachment

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:

• May be derived from acinar or tubular portions of gland
• Normal Iobulated appearance of gland is lost; acinar structure is disorganized 
• Cords and tubules of neoplastic cells on a fibrous stroma
• Lacrimal gland tumors according to a recent paper exploring similarities to WHO classification system (Giudice, 2021, Vet Pathol): 
  1. Pleomorphic carcinoma: Composed of epithelial (malignant) and myoepithelial (benign) neoplastic cells and areas of well-differentiated chondroid, myxoid, fibrous, or bone tissue
  2. Ductal carcinoma: Aggressive tumor with differentiation to the interlobular ducts, typically composed of irregularly shaped cystic nodules with central comedonecrosis, lined with carcinoma cells arranged in a cribriform pattern
  3. Epithelial-Myoepithelial carcinoma: Composed of 2 distinct cell populations, that is, epithelial and myoepithelial
  4. Adenoid cystic carcinoma: Composed of small, uniform cords, and/or solid nests, frequently surrounded by basophilic mucoid or hyaline material
  5. Myoepithelial carcinoma: Composed entirely of myoepithelial cells, proliferating in trabeculae or sheets
  6. Unclassified carcinomas: Those that do not clearly match the features of any entity in recent human WHO lacrimal gland tumor classification scheme 

 

DIFFERENTIAL DIAGNOSIS:

• Lacrimal gland adenoma (acinar or tubular): Smooth, expansile proliferation of well-differentiated acini of vacuolated columnar epithelial cells 
• Zygomatic salivary gland neoplasm: May infiltrate the orbit (zygomatic gland is infraorbital and a mixed salivary gland with a prominent mucinous component); histologically and biologically similar to lacrimal gland adenocarcinoma (lacrimal gland is supraorbital and a purely serous gland in cats); distinguishing lacrimal gland tumor from rare zygomatic tumor is based primarily on location; the zygomatic gland is ventromedial
• Inflammation and prolapse of the gland of the third eyelid ‘cherry eye’: non neoplastic condition where the gland of the third eyelid extrudes from the conjunctiva forming a mass-like appearance
• Conjunctival neoplasms:
  1. Meibomian gland neoplasm: Most common ocular neoplasm in dogs, histological appearance consistent with sebaceous adenomas; Meibomian gland epitheliomas are composed of densely packed sheets of basal reserve cells forming well defined lobules 
  2. Conjunctival squamous cell carcinoma (S-N01): Common aggressive conjunctival epithelium neoplasm in domestic animals, most common in cattle and horses 
  3. Granular cell tumor: Affects eyelids of canine, most often at the medial canthus, cytoplasm contains abundant PAS-positive granules 
  4. Apocrine cystadenomas (hidrocystomas): Benign lesion affecting the eyelids of domestic animals, multiple variably sized cysts lined by cuboidal epithelium; most often seen in Persian cats 
  5. Conjunctival melanocytic neoplasm: Second most common canine eyelid tumors arises from the conjunctiva and limbus
  6. Conjunctival vascular neoplasms: Arise in the conjunctiva lamina in dogs, cats, and horses; most likely a continuum from hemangioma to hemangiosarcoma; locally invasive and can metastasize 
  7. Conjunctival mast cell tumor: Sheets of well-differentiated granulated mast cells; most common tumor of feline eyelids
  8. Conjunctival papilloma: Exophytic neoplasm often arising from the bulbar conjunctiva; typically viral induced
  9. Conjunctival lymphoma: Ocular manifestations occur in dogs and cats often associated with systemic lymphoma

 

COMPARATIVE PATHOLOGY:

• Mouse: Rodents have a complex lacrimal gland system including both intra- and extraorbital lacrimal glands, in addition to the Harderian gland; Harderian gland neoplasms are lobulated, white to tan, and often fill the retro-bulbar space; Harderian gland adenocarcinomas are highly invasive with infiltration to the adjacent bone, overall less differentiation, and can metastasize to the lung; lacrimal gland papillary cystadenomas or solid adenomas are composed of well differentiated epithelial cells 
• Dogs: Equal prevalence of orbital sarcomas and carcinomas; approximately equal frequency of primary orbital tumors and those occurring as a result of local extension from the nose, mouth, or other structures

 

References:

1. Barthold SW, Griffey SM, Percy DH.  Pathology of Laboratory Rodents and Rabbits. 4^th ed. Ames, IA: Wiley-Blackwell; 2016:114.
2. Giudice C, Nordio L, Cadonici M, Perelli MN, Caniatti M. Epithelial lacrimal gland tumors in dogs and cats: Is the human WHO classification appropriate for animals? Vet Pathol. 2021 Sep;58(5):935-944.
3. Labelle P. The Eye. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:1379-1433.
4. Wilcock BP, Njaa BL. Special senses. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 1. 6^th ed. St. Louis, MO: Elsevier; 2016: 482

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