Michael H. Goldschmidt, MSc, BVMS, MRCVS, Diplomate ACVP Professor and Head, Laboratory of Pathology and Toxicology Chief, Surgical Pathology Department of Pathobiology
Frances S. Shofer, PhD, Adjunct Associate Professor of Epidemiology and Biostatistics
Introduction
Hepatoid glands are modified sebaceous glands only found in the dog. They are also referred to as perianal glands and circumanal glands. Hepatoid glands are found primarily in the perianal area, encircling the anus. They may also be found at the following sites:
- dorsal and ventral portions of the tail
- posterior area of the hindlimbs
- ventral abdomen, particularly the peripreputial skin
- lumbar area
- very occasionally in other sites, such as the head, neck and limbs
Hepatoid glands are ductless glands that continue to enlarge throughout the life of the dog under androgenic stimulation. Thus, in older male dogs they are commonly hyperplastic and subsequently may show progression to adenomas. It is likely that those cases which arise in females are associated with endogenous androgen production, probably by the adrenal gland.
The majority of hepatoid gland tumors are adenomas; fewer carcinomas are found on histopathologic evaluation of masses submitted for evaluation.
Hepatoid Gland Adenoma
Definition: A benign tumor of modified sebaceous glands comprised of cells that morphologically resemble hepatocytes.
Synonyms: Perianal Gland Adenoma, Circumanal Gland Adenoma
Epidemiology
|
Sex
|
N
|
Percent
|
| Female |
715
|
8% (21%)
|
| Female Spayed |
1800
|
21% (33%)
|
| Male |
4209
|
48% (25%)
|
| Male Castrated |
1993
|
23% (21%)
|
| (Normal Population %) |
|
Breeds at
Increased Risk |
N
|
Probability
|
OR
|
95%
Confidence Interval |
|
| Husky |
437
|
<0.0001
|
3.9
|
3.6
|
4.4
|
| Samoyed |
122
|
<0.0001
|
3.3
|
2.7
|
3.9
|
| Pekingese |
65
|
<0.0001
|
2.7
|
2.1
|
3.5
|
| Cocker Spaniel |
890
|
<0.0001
|
2.6
|
2.4
|
2.8
|
| Cockapoo |
86
|
<0.0001
|
2.3
|
1.8
|
2.8
|
| Weimeraner |
21
|
0.0358
|
2.1
|
1.1
|
3.9
|
| Lakeland Terrier |
179
|
<0.0001
|
2.0
|
1.7
|
2.3
|
| Brittany Spaniel |
81
|
<0.0001
|
1.9
|
1.5
|
2.4
|
| Shih Tzu |
215
|
<0.0001
|
1.7
|
1.5
|
2.0
|
| Mixed Breed |
2852
|
<0.0001
|
1.6
|
1.5
|
1.7
|
| Beagle |
273
|
<0.0001
|
1.6
|
1.4
|
1.8
|
|
Breeds at
Decreased Risk |
N
|
Probability
|
OR
|
95%
Confidence Interval |
|
| Bichon Frise |
43
|
0.0070
|
0.7
|
0.5
|
0.9
|
| German Shepherd |
239
|
<0.0001
|
0.7
|
0.6
|
0.7
|
| Labrador Retriever |
429
|
<0.0001
|
0.6
|
0.5
|
0.6
|
| Standard Poodle |
61
|
<0.0001
|
0.6
|
0.4
|
0.7
|
| Great Dane |
33
|
0.0001
|
0.5
|
0.4
|
0.8
|
| Miniature Schnauzer |
67
|
<0.0001
|
0.5
|
0.4
|
0.7
|
| Standard Schnauzer |
89
|
<0.0001
|
0.5
|
0.4
|
0.6
|
| Doberman Pinscher |
121
|
<0.0001
|
0.5
|
0.4
|
0.6
|
| English Bulldog |
15
|
0.0023
|
0.5
|
0.3
|
0.8
|
| Golden Retriever |
303
|
<0.0001
|
0.5
|
0.4
|
0.5
|
| Boston Terrier |
19
|
<0.0001
|
0.4
|
0.3
|
0.6
|
| Rhodesian Ridgeback |
9
|
0.0017
|
0.4
|
0.2
|
0.8
|
| Scottish Terrier |
25
|
<0.0001
|
0.4
|
0.3
|
0.6
|
| American Pit Bull Terrier |
14
|
<0.0001
|
0.3
|
0.2
|
0.5
|
| Maltese |
11
|
<0.0001
|
0.3
|
0.1
|
0.5
|
| English Setter |
9
|
<0.0001
|
0.3
|
0.1
|
0.5
|
| Jack Russell Terrier |
10
|
<0.0001
|
0.2
|
0.1
|
0.4
|
| Giant Schnauzer |
2
|
0.0028
|
0.2
|
0.0
|
0.7
|
| Boxer |
30
|
<0.0001
|
0.1
|
0.1
|
0.2
|
| Shar-Pei |
5
|
<0.0001
|
0.1
|
0.0
|
0.2
|
| Rottweiler |
15
|
<0.0001
|
0.1
|
0.0
|
0.1
|
| Gordon Setter |
1
|
<0.0001
|
0.1
|
0.0
|
0.4
|
| Breeds at Decreased Risk |
N | Probability | OR | 95% Confidence Interval |
|
| Bichon Frise | 43 | 0.0070 | 0.67 | 0.49 | 0.90 |
| German Shepherd | 239 | <0.0001 | 0.65 | 0.57 | 0.74 |
| Labrador Retriever | 429 | <0.0001 | 0.59 | 0.53 | 0.65 |
| Standard Poodle | 61 | <0.0001 | 0.56 | 0.44 | 0.73 |
| Great Dane | 33 | 0.0001 | 0.53 | 0.38 | 0.75 |
| Miniature Schnauzer | 67 | <0.0001 | 0.53 | 0.41 | 0.67 |
| Standard Schnauzer | 89 | <0.0001 | 0.52 | 0.42 | 0.65 |
| Doberman Pinscher | 121 | <0.0001 | 0.49 | 0.41 | 0.58 |
| English Bulldog | 15 | 0.0023 | 0.48 | 0.29 | 0.80 |
| Golden Retriever | 303 | <0.0001 | 0.46 | 0.41 | 0.51 |
| Boston Terrier | 19 | <0.0001 | 0.40 | 0.25 | 0.62 |
| Rhodesian Ridgeback | 9 | 0.0017 | 0.39 | 0.20 | 0.76 |
| Scottish Terrier | 25 | <0.0001 | 0.39 | 0.26 | 0.58 |
| American Pit Bull Terrier | 14 | <0.0001 | 0.27 | 0.16 | 0.47 |
| Maltese | 11 | <0.0001 | 0.27 | 0.15 | 0.49 |
| English Setter | 9 | <0.0001 | 0.26 | 0.13 | 0.50 |
| Jack Russell Terrier | 10 | <0.0001 | 0.23 | 0.12 | 0.43 |
| Giant Schnauzer | 2 | 0.0028 | 0.18 | 0.04 | 0.72 |
| Boxer | 30 | <0.0001 | 0.11 | 0.08 | 0.16 |
| Shar-Pei | 5 | <0.0001 | 0.09 | 0.04 | 0.22 |
| Rottweiler | 15 | <0.0001 | 0.07 | 0.04 | 0.12 |
| Gordon Setter | 1 | <0.0001 | 0.06 | 0.01 | 0.42 |
| Site | Percent |
| Perineum | 86.08% |
| Tail | 6.74% |
| Multiple Sites | 3.63% |
| Abdomen | 2.63% |
| Back | 0.67% |
| Hindlimb | 0.11% |
| Head | 0.08% |
| Thorax | 0.04% |
| Forelimb | 0.02% |
Clinical Presentation/Physical Exam Findings
- often nodular growths in the perianal area
- the overlying skin may be thinned and hair lost from the normally haired areas of the perianal tissue
- ulceration is common and may be due to pressure on the overlying skin by the tumor, or more likely due to traumatization
- extensive hemorrhage may result from the epidermal ulceration
- those tumors arising in non-perianal areas may be difficult to differentiate from other adnexal neoplasms
- these tumors may be exophytic (growing outward) or endophytic (growing inward)
Tumor Pathology
Gross Findings
- Elevated intradermal masses
- Vary in size from 0.5-10.0 cm in diameter
- Covered by hairless skin or often ulcerated and necrotic
- Cut sections are pale brown and multilobulated
- May show extensive hemorrhage and necrosis
- Invade underlying muscle and soft tissue
Microscopic Findings
Histopathology
The distinctive histopathologic feature of this tumor is differentiation to large hepatoid-like (hepatocyte-like) cells, which have an abundant eosinophilic cytoplasm.
- Trabeculae, islands and cords of tumor cells subdivided by a well vascularized connective tissue stroma
- Surrounded by a connective tissue capsule
- Small basophilic reserve cells are found at the periphery of the tumor lobules
- Reserve cells differentiate to cells with an abundant eosinophilic cytoplasm
- Cells have a central vesicular euchromatic nucleus and small nucleoli
- Mitoses are observed in the reserve cell layer
- Little nuclear atypia
- Ulceration, hemorrhage, necrosis and infiltration by inflammatory cells are common
- Proportion of cases will show foci of ductal differentiation (squamous metaplasia)
- Foci of cytoplasmic lipidization (sebaceous differentiation)
Cytology
- Large, cuboidal epithelial cells
- Occasionally isolated, but primarily found within adherent cell clusters
- Low nuclear:cytoplasm ratios; round nuclei; lacy chromatin; single, distinct nucleolus; occasionally binucleate
- Mild anisocytosis and anisokaryosis
- Abundant, slightly granular blue cytoplasm
- Flattened reserve cells occasionally observed at the periphery of a cluster
Clinical Behavior
Hepatoid gland adenomas continue to grow if not surgically removed. Most tumors are amenable to surgical excision, with the exception of advanced cases where multiple tumors encircle the entire perianal area.
Endogenous androgens, of testicular or adrenal gland origin, contribute to the growth of hepatoid gland adenomas. Tumors arising in the perianal area after the initial surgical removal of a hepatoid mass are more likely to be new tumors arising from continued stimulation of hyperplastic hepatoid glands by endogenous androgens, rather than recurrences of the initial tumors. Male dogs are often castrated to remove this source of endogenous androgen production. Production of endogenous androgens by the adrenal gland probably accounts for the development of solitary or multiple hepatoid gland tumors in intact or neutered bitches.
Hepatoid Gland Epithelioma
Definition: A tumor of low-grade malignancy characterized by a preponderance of basaloid cells, and a few cells with hepatoid differentiation.
Synonyms: Perianal Gland Epithelioma, Circumanal Gland Epithelioma
Clinical Presentation/Physical Exam Findings
- Physical exam findings are similar to hepatoid gland adenoma and carcinoma (see above)
Tumor Pathology
Gross Findings
- Gross appearance is similar to hepatoid gland adenoma and carcinoma (see above)
Microscopic Findings
- Preponderance of basaloid reserve cells
- Hepatoid cells may only be seen as individual cells within the tumor mass or as small aggregates
- Basaloid cells may show marked mitotic activity
- Little nuclear atypia
- Foci of ductal differentiation are found as small horn cysts
- Lymphatic invasion may occasionally be found at the periphery of a hepatoid gland epithelioma
Clinical Behavior
Hepatoid gland epitheliomas have low metastatic potential but will recur if inadequately excised.
Hepatoid Gland Carcinoma
Definition: A malignant tumor characterized by differentiation to hepatoid gland epithelium.
Synonyms: Perianal Gland Carcinoma, Circumanal Gland Carcinoma
Epidemiology
| Sex | N | Percent |
|
Female
|
19 | 5% (21%) |
|
Female Spayed
|
52 | 14% (33%) |
|
Male
|
214 | 60% (25%) |
|
Male Castrated
|
74 | 21% (21%) |
|
( Normal Population %)
|
| Breeds at Increased Risk |
N | Probability | OR | 95% Confidence Interval |
|
| Husky | 37 | <0.0001 | 7.8 | 5.6 | 11.0 |
| Alaskan Malamute | 6 | 0.0003 | 7.1 | 3.2 | 16.1 |
| Samoyed | 9 | <0.0001 | 5.5 | 2.8 | 10.6 |
| Old English Sheepdog | 5 | 0.0317 | 2.9 | 1.2 | 7.0 |
| Shih Tzu | 14 | 0.0011 | 2.7 | 1.6 | 4.6 |
| Mixed Breed | 111 | 0.0024 | 1.4 | 1.1 | 1.8 |
| Breeds at Decreased Risk |
N | Probability | OR | 95% Confidence Interval |
|
| Labrador Retriever | 10 | <0.0001 | 0.3 | 0.2 | 0.6 |
| Golden Retriever | 4 | <0.0001 | 0.1 | 0.1 | 0.4 |
| Boxer | 1 | <0.0001 | 0.1 | 0.0 | 0.7 |
| Site | Percent |
| Perineum | 78.1% |
| Abdomen | 9.0% |
| Tail | 6.3% |
| Back | 3.3% |
| Head | 1.7% |
| Multiple Sites | 1.0% |
| Hindlimb | 0.3% |
| Thorax | 0.3% |
Clinical Presentation/Physical Exam Findings
- The appearance is similar to hepatoid gland adenoma and epithelioma
- The diagnosis of carcinoma is best made clinically by finding metastatic spread to the regional lymph nodes
Tumor Pathology
Gross Findings
- Gross appearance is similar to hepatoid gland adenoma and epithelioma
- Carcinomas may be more invasive into the surrounding tissue.
Microscopic Findings
- Carcinomas lack the well defined and organized lobular pattern seen with adenomas and epitheliomas
- Peripheral invasion
- Primitive basaloid cells show greater nuclear pleomorphism and hyperchromatism
- Cells showing hepatoid differentiation have cytoplasm that stains less eosinophilic and is often vacuolated
- Nuclei are pleomorphic and nucleoli are prominent
- Mitoses will be found in the reserve cells and the differentiated cells
- Anaplastic tumors may show only focal hepatoid cell differentiation
Clinical Behavior
Hepatoid gland carcinomas are likely to metastasize to the sacral and sublumbar lymph nodes. The incidence of metastasis probably ranges from 10 to 30%.
References
- Goldschmidt, M.H., & Hendrick, M.J. (2002). Tumors of the skin and soft tissue. In D.J. Meuten (Ed.), Tumors in domestic animals 4 th ed (pp. 45-119). Iowa: Iowa State Press
- Goldschmidt, M.H., & Shofer, F.S. (1998). Skin tumors of the dog and cat. Woburn, MA: Butterworth-Heinemann
- Gross, T.L., Ihrke, P.J., & Walder, E.J. (1992). Veterinary dermatopathology: A macroscopic and microscopic evaluation of canine and feline skin disease. (pp. 327-485). St. Louis, Missouri: Mosby Year Book
- World Health Organization (1998). Histological classification of epithelial and melanocytic tumors of the skin of domestic animals (2 nd series, vol 3). Washington, DC: Armed Forces Institute of Pathology
- Yager, J.A. & Wilcock, B.P. (1994). Color atlas and text of surgical pathology of the dog and cat. Ontario, Canada: Mosby Year Book
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