Sertoli cell tumor/mixed germ cell-stromal cell tumor as separate neoplasms in a bilaterally cryptorchid dog

Abstract

An 11-year-old miniature poodle dog was presented with bilateral flank alopecia, gynecomastia, severe thrombocytopenia, and preputial edema. Based on characteristic clinical and hematological findings of hyperestrogenism and the presence of a caudal abdominal mass, a Sertoli cell tumor (SCT) was diagnosed. After a platelet concentrate transfusion, the SCT was surgically removed in addition to an atrophied contralateral testicle containing a mixed germ cell-stromal cell tumor. Recovery was uneventful. This combination of different neoplasms in separate testicles has yet to be documented.

Key clinical message:

This case of a SCT/mixed germ cell-stromal cell tumor combination in a bilaterally abdominal cryptorchid dog highlights common clinical signs associated with hyperestrogenism and the management of estrogen-induced myelotoxicity causing severe thrombocytopenia.

An 11-year-old miniature poodle dog, which was reported by the rescue organization to be neutered, was presented because of bilaterally symmetric flank alopecia, gynecomastia, and edematous preputial enlargement of unknown duration. Upon physical examination, the dog was in poor body condition (BCS 1.5/5), had diffuse brown, flaky seborrheic dermatitis, an enlarged soft prostate, and no petechiae or ecchymosis. Upon palpation, a firm, smooth, freely movable mass measuring approximately 7 × 7 cm was detected in the caudal abdomen.

Abdominal radiography confirmed the presence of a soft tissue mass in the caudal abdomen, near the cranial margin of the bladder (Figure 1). No thoracic metastasis was detected on thoracic radiographs. Hematological analysis revealed a mild, non-regenerative, normocytic, hypochromic anemia, and a marked thrombocytopenia (Table 1). The leukogram was normal. There was a mild hyperproteinemia with a mild hypoalbuminemia and hyperglobulinemia [total protein: 78 g/L, reference range (RR): 50 to 74 g/L; albumin: 22 g/L, RR: 27 to 44 g/L; globulin: 56 g/L, RR: 16 to 36 g/L]. Urinalysis revealed a marked pyuria and moderate hematuria [WBC: > 100/high power field (hpf ); RBC: 20 to 30/hpf ] but no bacteria were observed microscopically or cultured. The dog was treated with pradofloxacin (Veraflox; Bayer Animal Health, Mississauga, Ontario), 15 mg, PO, q24h, for 10 d. Based on these findings, a Sertoli cell tumor was suspected; however, surgery was delayed due to the severe thrombocytopenia. Further blood analysis was completed the following day. The anemia was relatively unchanged, there was now a mild leukocytosis and neutrophilia, and the platelets were still markedly decreased (Table 1). The prothrombin time (PT) and partial thromboplastin time (PTT) were within normal ranges (PT: 6.9 s; PTT: 15.6 s). Blood typing and crossmatching were completed to prepare a blood transfusion in the event of uncontrolled hemorrhage during the surgical procedure. Due to the severe thrombocytopenia and risk for spontaneous hemorrhage during surgery, a concentrated platelet transfusion was administered the day before surgery and a follow-up complete blood (cell) count (CBC) the day of surgery showed the platelets were now only moderately decreased (Table 1).

Figure 1.

Abdominal radiograph of an 11-year-old miniature poodle dog showing the cryptorchidic enlarged left testicle (arrows).

Table 1.

Hematological data before and after surgery.

	Reference range	7 days before surgery	5 days before surgery	Day of surgerya	3 days after surgery	7 days after surgery	2.5 months after surgery
Parameter
Platelets (×109/L)	143 to 448	13	34	58	30	63	314
RBC (×1012/L)	5.4 to 8.7	5.1	5.0	4.7	5.1	5.3	7.9
Hematocrit (L/L)	0.38 to 0.57	0.37	0.34	0.34	0.37	0.40	0.56
Hemoglobin (g/L)	134 to 207	116	117	114	125	126	172
Reticulocytes (103/μL)	10 to 110	15.3	15.0	18.8	15.6	15.6	36.3
WBC (×109)	4.9 to 17.6	11.7	18.2	10.5	7.8	7.0	5.1
Neutrophils (×109)	2.9 to 12.7	9.5	15.4	7.7	5.6	5.0	2.56

^aPlatelet rich transfusion the previous day.

The dog was premedicated with midazolam (Midazolam; Sandoz, Boucherville, Quebec), 0.3 mg/kg body weight (BW), IV, and hydromorphone (HYDROmorphone HP 10; Sandoz), 0.1 mg/kg BW, IV, induced with IV alfaxolone (Alfaxan; Multidose; Jurox, North Kansas City, Missouri, USA), 3 mg/kg BW, IV, and maintained on isoflurane. The abdomen was clipped and aseptically prepared. A 7-cm midline incision was made into the abdomen. The abdomen was explored and an enlarged, vascular left abdominal testicle measuring 5 cm × 4 cm was visualized. Using a 3-hemostat clamp technique with 2 Miller’s knots as ligation, the spermatic cord was transected. Upon further exploration, an atrophied right testicle measuring 1 cm × 1 cm was also identified within the abdomen and the spermatic cord was transected in a similar manner. The incision was closed in 3 layers with 2-0 PDS (Ethicon, Somerville, New Jersey, USA) (rectus sheath) and 3-0 PDS (subcutaneous and skin).

On histopathologic examination, the larger left testicle was diagnosed as containing a Sertoli cell tumor. The neoplastic cells showed moderate anisocytosis and anisokaryosis, and an increased mitotic rate (23 per 10 hpf ). The smaller right testicle was diagnosed as containing a mixed germ cell-sex cord stromal tumor with moderate anisocytosis and anisokaryosis and frequent mitotic figures.

The dog was rechecked daily for 3 d after surgery for evidence of spontaneous hemorrhage. No petechiae or ecchymosis were observed. A repeat CBC was performed at 3 and 7 d after surgery and showed the beginning of recovery in the thrombogram and hemogram. Two and a half months later, all values had returned to normal (Table 1). The preputial swelling, alopecia, and gynecomastia gradually resolved over these months. No further clinical problems have been reported.

Discussion

Primary testicular neoplasms are the most common testicular tumors in dogs (1). Testicular tumors are histologically classified into sex cord-stromal tumors [Sertoli cell tumors (SCTs) and Leydig/interstitial cell tumors], germ cell tumors (seminomas), and mixed germ cell-sex cord stromal tumors (MGCSCTs) (1,2). Multiple retrospective studies have found that MGCSCTs and SCTs are the 2 least prevalent testicular tumors while interstitial (Leydig) cell tumors and seminomas are most common (3,4).

Although this dog was presented as neutered, being a rescued animal, there was no documentation to confirm this claim. Only 15% of cryptorchid dogs have bilaterally retained abdominal testicles and miniature poodles have previously been identified as having an increased risk for cryptorchidism (5). Cryptorchidism was found to be a significant risk factor for the development of both MGCSCTs and SCTs (4). Cryptorchid testes are approximately 13 to 14 times more likely to develop a neoplasm compared with scrotal testes, suggesting that cryptorchidism contributes to testicular tumorigenesis (4,6).

This case is unique in that both retained testes had separate and different neoplasms. While there have been previous reports of SCT/interstitial and SCT/seminoma combinations (26% and 21% of reported combinations, respectively), the author could not find any reports of an SCT/MGCSCT combination (3,7).

This case also highlights common characteristic presenting signs associated with a SCT. These include an enlarged prostate, non-pruritic symmetrical alopecia, thinning of the skin, hyperpigmentation, gynecomastia, and a pendulous edematous prepuce (7,8). In affected male dogs, 25% to 50% with a SCT experience this feminization syndrome due to estrogens secreted by the tumor (8). Feminization syndrome appears more common for abdominal SCTs (8).

Along with feminization syndrome, the estrogens secreted by a SCT can also affect the bone marrow (9). Typical hematological changes associated with estrogen-induced myelotoxicity include a non-regenerative anemia, thrombocytopenia, and leukocytosis followed by a leukopenia. Prognosis is guarded when all elements are present (9). The mechanism of estrogen-induced myelotoxicity appears to involve the production of myelopoiesis-inhibitory factor by thymic stromal cells in the presence of high estrogen levels. However, the exact mechanism is unknown (10,11).

While the anemia and leukocytosis in this dog were mild, the thrombocytopenia was severe. Both pre-transfusion platelet counts were below the range in which spontaneous clinical hemorrhage can occur (12). A platelet concentrate transfusion was administered as it is thought to be useful for prophylactic therapy when the thrombocytopenia is due to decreased platelet production (12).

Another interesting feature of this case was the increased mitotic activity seen on histology, suggesting an increased possibility for malignancy. Typically, mitotic figures are rare in SCTs, averaging 0 to 1 per hpf, versus the 23 per 10 hpf reported here (3). Only about 10% to 20% of SCTs are malignant with metastasis occurring most commonly to the inguinal, iliac, and sublumbar lymph nodes, as well as lungs, liver, and spleen (13). Thoracic radiographs showed no sign of metastasis in this dog at the time of surgery; however, lymph node aspirates were not taken.