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Apocrine Gland Tumors

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Supported by the Savannah and Barry French Poodle Memorial Fund
University of Pennsylvania School of Veterinary Medicine
Last Modified: August 21, 2005

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

Apocrine glands have both a secretory and a ductal component. The secretion empties into the infundibulum of the hair follicle (epitrichial). The cells that make the secretion are columnar with copious granular eosinophilic cytoplasm and the nuclei are located in the base of the cell. The secretion is produced when the apical portion (top) of the cell is cleaved into the glandular lumen. The secretory cells are surrounded by myoepithelial cells which are surrounded by the basal lamina zone. The apocrine duct is lined by cuboidal epithelial cells that form a double layer.

• Apocrine Adenoma
• Apocrine Ductal Adenoma
• Complex & Mixed Apocrine Adenoma
• Apocrine Carcinoma
• Apocrine Ductal Carcinoma
• Complex & Mixed Apocrine Carcinoma
• References

Apocrine Adenoma

Definition: A benign tumor with differentiation to apocrine secretory epithelium.

Epidemiology

Clinical Presentation/Physical Exam Findings

• Located primarily in the dermis and subcutaneous tissue

• Range in size from 1.0 cm to 4.0 cm in diameter.
• Usually soft, well demarcated, and covered by normal epidermis.
• Ulceration and secondary infection is common with larger tumors.

Tumor Pathology

Gross Findings

• A variety of patterns may be seen on cut section.
• Some may be composed of multiple large cysts separated by thick septa, or many smaller cysts.
• These cysts are filled with fluid that can range from clear to brown (due to inspissation of the secretion).

Microscopic Findings

Three different histologic patterns may be found:

1. Glandular tumors
• consist of multiple small islands of glandular epithelium separated by fine fibrovascular connective tissue trabeculae
• may be an eosinophilic secretion within the glandular lumina 
• single layer of lining cells are cuboidal with abundant granular eosinophilic cytoplasm, basally located nuclei and may exhibit decapitation secretion
• accumulation of secretion within the glandular lumina may result in attenuation of the lining epithelial cells
• may have numerous plasma cells and ceroid containing macrophages within the interstitial stroma
2. Cystic tumors
• have larger glandular lumina filled with secretion and are often lined by an attenuated epithelium
3. Papillary tumors:
• show invaginations of the epithelium into the glandular lumina, supported by the fibrovascular stoma
• may have numerous plasma cells and ceroid containing macrophages within the interstitial stroma.

Clinical Behavior

Surgical excision is curative, with no recurrence reported.

Apocrine Ductal Adenoma

Definition: A benign tumor with differentiation to apocrine ductal epithelium.

Epidemiology

Clinical Presentation/Physical Exam Findings

• These tumors are solitary, circumscribed, multinodular, dermal and subcutaneous masses.
• Usually 2 cm or larger in diameter

Tumor Pathology

Gross Findings

• The overlying epidermis may lose its hair, but ulceration is uncommon.

Microscopic Findings

• nodular masses, often involve both the dermis and subcutis 
• may have central cystic degeneration
• multilobulated 
• proliferation of a double layer of basophilic epithelial cells separated by a thin fibrous stroma 
• cells lining the lumina may have scant clear cytoplasm with small hyperchromatic nuclei 
• cells adjacent to the basal lamina zone may be more fusiform with little cytoplasm and a euchromatic nucleus
• little cellular or nuclear pleomorphism 
• few mitoses 
• some tumors show foci of squamous differentiation with small deposits of keratin, differentiation to the infundibular portion of the apocrine duct 

Clinical Behavior

Surgical excision is curative, with no recurrence reported.

Complex and Mixed Apocrine Adenoma

Introduction

Definition:Complex (compound) apocrine tumors have glandular and myoepithelial cells. Mixed apocrine tumors show metaplastic change of the myoepithelium to cartilage or bone.

These are uncommon tumors. A histopathologic evaluation is required for a definitive diagnosis. The epithelial component must be evaluated to determine the malignant potential of these tumors.

Epidemiology

Note: Site distribution table for Complex and Mixed Apocrine Adenoma is included in the Apocrine Adenoma Site Distribution Table. Please see above.

Clinical Presentation/Physical Exam Findings

• These tumors present as very firm, well-defined intracutaneous masses.

Tumor Pathology

Gross Findings

• Well encapsulated intradermal mass.

Microscopic Findings

• well defined dermal mass
• proliferation of the epithelial elements as described for glandular apocrine adenoma
• foci of myoepithelial proliferation  seen as aggregates of fusiform to stellate cells within a myxoid matrix
• In mixed tumors, the myoepithelial cells undergo chondroid or osseus differentiation.

Clinical Behavior

Surgical excision is curative, with no recurrence reported.

Apocrine Carcinoma

Definition: A simple malignant tumor with differentiation to apocrine secretory epithelium.

Epidemiology

Clinical Presentation/Physical Exam Findings

• These tumors may present as solid, nodular intradermal masses.
• Range in size from 0.3 to 5.0 cm in diameter.
• The epidermis covering the tumor usually becomes ulcerated.
• The masses may feel firm and fibrous due to the accumulation of connective tissue in the subcutaneous layer (desmoplasia).

Inflammatory Apocrine Carcinoma (IAC):

• Some tumors may develop as a swiftly enlarging erosive and ulcerative dermatitis.
• Ulcerated areas and surrounding hair coat are covered with a serous crust due to the inflammation.
• This subtype has a predilection for the inguinal and axillary regions of the body.

Tumor Pathology

Gross Findings

• Nodular form
• It is tan to white and possible divided into lobules by thin trabeculae.
• There may be infiltrative areas of fibrosis surrounding the mass which resemble a capsule.
• Inflammatory form
• These usually only have dermal and superficial subcutaneous involvement.
• Those that arise in the inguinal and axillary area may be associated with metastasis to regional lymph nodes and possibly to the lungs.
• The nodes have foci that appear white and firm, which replace the normal parenchyma.

Microscopic Findings

Histopathology

• may have a solid, tubular or cystic morphology
• cystic tumors may show papillae extending into the cyst lumina
• dermal and subcutaneous infiltration, often with an accompanying desmoplastic response, may be observed
• degree of differentiation of the tumor cells is quite variable
• well differentiated tumors have an abundant eosinophilic cytoplasm
• may show apical blebbing, large ovoid euchromatic nuclei with prominent nucleoli
• may exhibit modest nuclear and cellular pleomorphism and mitotic activity
• can be differentiated from the benign tumors by their invasive nature
• poorly differentiated tumors the cells are very pleomorphic and anaplastic, but the eosinophilic cytoplasm of the tumor cells is retained
• these tumors often evoke a strong desmoplastic host response
• invasion of dermal lymphatics by tumor cells is a relatively common occurrence, with metastasis to regional lymph nodes and lungs
• Inflammatory apocrine carcinoma
• epidermal ulceration is common
• superficial dermal lymphangiectasia with extensive proliferation of tumor cells within the lumina of the lymphatics
• cells are frequently pleomorphic and anaplastic
• may show neutrophil phagocytosis

Cytology

• moderately large to large cells
• occasionally isolated, generally found within adherent cell clusters and rosettes
• moderate anisocytosis
• moderately high to very high N:C ratio
• round nuclei; fine to moderately coarse ropy chromatin; variably sized prominent nucleoli
• variably vacuolated light blue cytoplasm

NOTE: Apocrine carcinomas are very similar histologically to mammary carcinomas.

Clinical Behavior

Many of these tumors will metastasize to regional lymph nodes and possibly the lungs. Inflammatory apocrine carcinomas have been shown to do this most frequently, along with those carcinomas that are invasive and cause a desmoplastic response. Inflammatory apocrine carcinomas produce a diffuse interstitial pattern in the lung on radiographic evaluation. Small tumors that are removed soon after they are found, and well differentiated tumors, are usually cured via wide excision. Less well differentiated tumors will spread to regional lymph nodes and lungs.

Apocrine Ductal Carcinoma

Introduction

Definition:A malignant tumor with differentiation to apocrine ductal epithelium.

These tumors are rare.

Epidemiology

Note: Site distribution table for Apocrine Ductal Carcinoma is included in the Apocrine Carcinoma Site Distribution Table. Please see above.

Clinical Presentation/Physical Exam Findings

• These tumors present as very firm, well-defined intracutaneous masses.

Tumor Pathology

Gross Findings

• intradermal and subcutaneous mass(es)

Microscopic Findings

• sheets of neoplastic cells show focal lumen formation, lined by a double layer of epithelial cells
• accumulation of eosinophilic secretion within the lumina
• cells exhibit nuclear pleomorphism, hyperchromasia and mitotic activity
• foci of squamous differentiation may be present
• invasion of surrounding stroma is often seen at the edges of the tumor
• lymphatic invasion with nodal metastasis is uncommon

Clinical Behavior

These tumors rarely recur after wide surgical excision. Metastases are very infrequently found.

Complex and Mixed Apocrine Carcinoma

Introduction

Definition: Complex (compound) apocrine tumors have malignant proliferation of glandular cells and accompanying proliferation of myoepithelial cells. Mixed apocrine tumors show metaplastic change of the myoepithelium to cartilage or bone.

These are uncommon tumors. A histopathologic evaluation is required for a definitive diagnosis. The epithelial component must be evaluated to determine the malignant potential of these tumors.

Clinical Presentation/Physical Exam Findings

• These tumors present as very firm intracutaneous masses.

Tumor Pathology

Gross Findings

(See apocrine carcinoma above)

Microscopic Findings

• differs from its benign counterpart only in the malignant appearance of the glandular epithelial component
• uncommon to see malignant changes of the myoepithelial cells
• in rare instances when the epithelial and mesenchymal components of this tumor both exhibit malignant changes, the tumor is referred to as an apocrine carcinosarcoma

Clinical Behavior

Epithelial components will metastasize via lymphatics to the regional lymph nodes and lungs.

• 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