Case Report: Disorder of Sexual Development in a Chinese Crested Dog With XX/XY Leukocyte Chimerism and Mixed Cell Testicular Tumors

Abstract

A 10-year-old intact female Chinese Crested dog was presented for evaluation and further diagnostics due to persistent symptoms of vulvar swelling, vaginal discharge, and an 8-year history of acyclicity. At presentation, generalized hyperpigmentation and truncal alopecia were identified, with no aberrations of the female phenotype. Vaginal cytology confirmed the influence of estrogen at multiple veterinary visits, and hormonal screening of progesterone and anti-Mullerian hormone indicated gonadal presence. Based on findings from abdominal laparotomy and gonadectomy, the tissue was submitted for histopathology. Histopathologic evaluation identified the gonads to be abnormal testes containing multiple Sertoli and interstitial (Leydig) cell tumors. The histopathologic diagnosis of testes and concurrent normal external female phenotype in the patient lead to a diagnosis of a disorder of sexual development (DSD). Karyotype evaluation by conventional and molecular analysis revealed a two cell line chimeric pattern of 78,XX (80%) and 78,XY (20%) among blood leukocytes, as well as a positive PCR test for the Y-linked SRY gene. Cytogenetic analysis of skin fibroblasts revealed the presence of 78,XX cells exclusively, and PCR tests for the Y-linked SRY gene were negative in the hair and skin samples. These results are consistent with an XX/XY blood chimerism. This is one of the few case reports of a canine with the diagnosis of leukocyte chimerism with normal female phenotypic external genitalia. This case illustrates a distinct presentation for hormonally active Sertoli cell tumorigenesis and demonstrates surgery as a curative treatment option for clinically affected patients.

Keywords: Leydig cell tumor; Sertoli cell tumor; canine; chimerism; disorder of sexual development (DSD).

Figure 1

(A) Perineal region and vulva of patient on presentation to VMCVM; (B) Noted bilateral, non-pruritic alopecia on presentation of patient to VMCVM, and (C) Patient 6 months after recovering from surgery—noted significant hair regrowth.

Figure 2

A subgross image (A) of the tissues reveals irregular testicular tissue with alternating areas of solid masses and cystic change, focally bordered by epididymal and vascular structures (B). Within the tissue are multifocal Leydig cell tumors (C) characterized by nests of polygonal cells with granular to vacuolated eosinophilic cytoplasm (D), that occasionally contain eosinophilic granules (D, insert). Remaining tubules are expanded by massively proliferative Sertoli cells forming intratubular neoplasi (E), characterized by haphazard piles of elongated cells (F) that occasionally palisade around a central eosinophilic matrix (F, insert).

Figure 3

Cytogenetic and molecular cytogenetic analysis of blood leukocytes. (A) G-banded karyotype (left) and corresponding metaphase (right) of a 78,XX cell; (B) G-banded karyotype (left) and corresponding metaphase (right) of a 78,XY cell; (C) FISH with cat X chromosome painting probe (green; arrows) in a 78,XX cell, and (D) FISH with cat X chromosome painting probe (green; arrow) and dog Y-specific TSPY probe (red; arrow) in a 78,XY cell.

Figure 4

Agarose gel images showing PCR results with the sex determining region in Y, SRY (left panel) and X-linked androgen receptor gene, AR (control) on DNA templates from blood lymphocytes, hair, and skin fibroblasts together with male and female controls.