Signalment:  

6-year-old male, Rhesus Macaque, (Macaca mulatta)An encapsulated subcutaneous mass was noted near the right nipple. It was removed and submitted for analysis. On physical exam no other abnormalities were noted.

Gross Description:  

The tissue sample (biopsy) measured 1.8 x 1.5 x 1.0 cm. The mass is firm, slightly nodular and yellow to white in color. It is encapsulated in a well demarcated capsule.

Histopathologic Description:

The slide consists of a well demarcated neoplasm surrounded by a layer of smooth muscle lined by flattened epithelial cell. There are some pockets of normal glandular tissue in the surrounding soft tissue. The neoplastic nodules appear to be mostly solid with rare ductal and tubular structures. The ductal structures are lined by pleomorphic epithelial cells with loss of polarity and piling up of cells (Figs. 2-1, 2-2). Some cells have clear cytoplasmic vacuoles. The nuclei have stippled chromatin with single nucleoli and are centralized in the cell. Roughly 1 mitotic figure per 40X field is seen. Multiple sections of the neoplasm fail to show invasion into surrounding soft tissue. Original tumor sections were subdivided to prepare conference slides.

Morphologic Diagnosis:  

Mammary Gland: ductular carcinoma in situ (DCIS)

Condition:  

Ductular carcinoma in-situ

Contributor Comment:  

Mammary gland tumors are uncommon in macaques. It is still unclear whether the low cancer rate observed in macaques is true resistance or if insufficient lifespan studies have been conducted to see whether higher cancer rates occur in aged populations.(8) Ductular carcinoma in situ (DCIS) are neoplasms that have neoplastic cells limited to ducts. This is distinguished from lobular carcinoma in situ (LCIS) where cells extend into lobules. Occasionally it is difficult to morphologically distinguish LCIS from ductular carcinoma in situ DCIS. A potential marker to distinguish DCIS from LCIS is E-cadherin since E-cadherin protein expression is lost in LCIS, while it remains in cases of DCIS.(6,8)

Differentiation between DCIS and LCIS is crucial in humans because management strategies differ greatly between the two types.(7) In humans, estrogens have been hypothesized as contributing to the formation of mammary tumors. Estrogen stimulates the mitosis of breast epithelial cells regardless of the gender and can enhance unregulated growth of mammary tissue.(1) This particular case is interesting because it represents a mammary gland carcinoma in a male, which has been rarely reported. One report gives an incidence rate of 1.1% in a long term study of untreated animals.(8) This rate is similar to that seen in men, accounting for 0.8% of all the cases of mammary carcinoma. Most mammary carcinoma in human males is ductal in origin with the majority being invasive. Mammary gland carcinoma in men has been reported to be linked to testicular abnormalities, Klinefelter syndrome, familial history of breast cancer, infertility and breast discharge. They tend to be estrogen and progesterone receptor positive.(3)

JPC Diagnosis:  

Mammary gland: Ductular carcinoma in-situ

Conference Comment:  

This case was reviewed in consultation with the AFIP Department of Gynecologic and Breast Pathology, who agreed with the contributors diagnosis, and further commented that the DCIS appeared to involve a papilloma, based on the presence of papillary cores within the lesion which are lined by a monotonous proliferation of epithelial cells consistent with DCIS. They also noted the focal presence of myoepithelial cells in some of the papillary cores.

During the post conference, part of the discussion focused on general features distinguishing benign from malignant tumors. These features include pleomorphism, nuclear morphology, appearance of mitotic figures and overall mitotic rate, polarity, and invasiveness.

In malignant tumors, both cells and nuclei generally display greater variation in size and shape than do their benign counterparts. Cells can be much larger or smaller than adjacent cells, with similar variation in nuclear size. These changes are referred to as anisocytosis and anisokaryosis, respectively. In malignant tumors, nuclei often contain an abundance of DNA and stain much darker (hyperchromatic). The nuclear to cytoplasmic ratio can also approach a 1:1 ratio from the normal 1:4 to 1:6 ratio. Mitotic figures are more abundant in malignant tumors than in benign tumors. Often, malignant tumors also have bizarre mitotic figures forming abnormal shapes and patterns that do not resemble the normal mitotic rearrangement of chromosomes. These cells often produce multipolar spindles, which can create a highly unusual cellular appearance in relation to neighboring cells. Malignant tumors are generally faster growing neoplasms with growth occurring in a more disorganized, haphazard fashion (often referred to as loss of polarity). Malignant tumors also tend to invade surrounding tissue and metastasize to regional lymph nodes and other organ systems, whereas benign tumors stay in the location of origin. There can be a wide range of morphologic appearances within tumors depending on the specific type of tumor and the tissue involved, so these guidelines are meant as a general rule and are subject to vary from one type of neoplasm to the next. (4)

Mammary gland lesions have been reported in numerous lab animals and domestic species, and a few of the more common of these were discussed during the post-conference session. A chart listing the species discussed during this session and the changes in each species is included below.

Species	Mammary change	Cause
Rat	Fibroadenoma (S-D strain)	Increase in prolactin
Rabbit	Mammary dysplasia	Pituitary tumor
Mouse	FVB/N mice hyperplasia of mammary glands Mammary tumors	Proliferation of prolactin secreting cells in pars distalis Mammary tumor viruses (MMTVs)
Cat	Fibroepithelial hyperplasia	Progesterone administration (Ovaban other iatrogenic hormones)
Canine	Gynecomastia	Sertoli cell tumor

(2,5)

References:

1. Clemons M, Goss P: Estrogen and the risk of breast cancer. N Engl J Med 344:276-285, 2001
2. Foster RA, Ladd PW: Male genital system. In: Jubb, Kennedy and Palmers Pathology of Domestic Animals, ed. Maxie MG, 5th ed., pp. 596-597. Elsevier, Philadelphia, Pennsylvania, 2007
3. Giordano SH, Buzdar AU, Hortobagyi GN: Breast cancer in men. Annals of Internal Medicine 137:678-687. Primatology 2001; 30:121126
4. Kumar V, Abbas AK, Fausto N: Neoplasia. In: Robins and Cotran Pathologic Basis of Disease, ed. Kumar V, Abbas AK, Fausto N, 7th ed., pp. 272-276. Elsevier, Philadelphia, Pennsylvania, 2005
5. Percy DH, Barthold SW: Pathology of Laboratory Rodents and Rabbits, 3rd ed., pp.116-117, 170-171, 306. Blackwell Publishing, Ames, Iowa, 2007
6. Moll R, Mitze M, Frixen UH: Differential loss of E-cadherin expression in infiltrating ductal and lobular breast carcinomas. Am J Pathol 143:173142, 1993
7. Schnitt SJ, Morrow M: Lobular carcinoma in situ: current concepts and controversies. Semin Diagn Pathol 16:20923, 1999
8. Wood CE, Usborne A, Tarara R, Starost MF: Hyperplastic and neoplastic lesions of the mammary gland in macaques. Vet Pathol 43:471483, 2006

Click the slide to view.

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2-1. Mammary gland, macaque.

2-2. Mammary gland, macaque.

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