Malignant nerve sheath tumor infiltrating the epididymis of an inguinal cryptorchid testis in a domestic shorthair cat

Abstract

Case summary

An 8-year-old, male domestic shorthair cat presented with a firm mass in the right inguinal region. Microscopic evaluation of the surgically excised mass revealed a soft tissue sarcoma (STS), with features most consistent with a malignant nerve sheath tumor (MNST), infiltrating the epididymis of an atrophic intra-inguinal cryptorchid testis. The tumor showed classical Antoni A and B patterns on histopathology, with spindle cells arranged in short interlacing fascicles, and a mitotic count of 14 per 10 high-power fields, supportive of a malignant form. Immunohistochemistry revealed positive labeling of the neoplastic cells for the markers S-100 and vimentin, while labeling for glial fibrillary acidic protein was negative; these findings supported the diagnosis of MNST.

Relevance and novel information

Nerve sheath tumors (NSTs) in cats are not uncommon neoplasms, typically arising from cutaneous or subcutaneous nerves of the head, neck or limbs. NSTs arising from visceral sites appear relatively rare, and there are no previously published reports describing such a tumor associated with a cryptorchid testis. This case expands the documented anatomical distribution of feline NSTs and underlines the fact that they may occur at visceral sites as well as within the skin and subcutis. It also highlights the need to include NST in the list of tumors that may arise within or be associated with the testes, cryptorchid or otherwise, and to consider neoplasia arising within a cryptorchid testis as a potential differential for an inguinal swelling in an intact male cat.

Plain language summary

A nerve tumor affecting a retained testicle in a cat

We describe a case of a malignant tumor in a cat that originated from the cells surrounding nerves. The tumor was found in an unusual location – associated with a retained testicle located in the inguinal (groin) region. An 8-year-old male cat was presented to a clinic because of a firm swelling in the groin area. Surgery was performed to remove the mass, which was initially suspected to be an abnormal retained testicle. Histopathological examination revealed that the mass was a malignant peripheral nerve sheath tumor infiltrating adjacent structures, including the epididymis. Tumors of this type have been reported in cats, but they are usually located in the skin or subcutaneous tissues. To our knowledge, association with a retained inguinal cryptorchid testis has not been previously described. This case highlights two important points. First, peripheral nerve sheath tumors in cats may occur in unusual internal locations and should not be considered exclusively cutaneous tumors. Second, when a male cat presents with inguinal swelling – particularly in association with cryptorchidism – neoplasia should be included among the differential diagnoses.

Introduction

Nerve sheath tumors (NSTs; formerly referred to as peripheral nerve sheath tumors), a form of soft tissue sarcoma (STS), are neoplasms arising from Schwann cells, perineurial cells or intraneural fibroblasts, and are being increasingly recognized in cats. In the largest retrospective study to date, Schulman et al ¹ reported that feline NSTs accounted for approximately 7% of all cutaneous tumors, most frequently occurring on the head, including the periocular region, ² as well as the neck and limbs, with fewer cases involving the trunk or deep soft tissues.^1,3 Classification remains challenging because of overlapping histological features, variable immunophenotypes and considerable morphological diversity. ⁴ Although benign schwannomas and neurofibromas form the majority, malignant NSTs (MNSTs) can also arise. ¹ In the study by Schulman et al, ¹ tumors with a mitotic count of four or more per 10 high-power fields (HPFs; 400×; 2.37 mm²) also tended to have features such as hypercellularity, significant nuclear atypia and/or tumor necrosis, and were considered histologically malignant. Metastatic disease appears rare with malignant NSTs,^5,6 and for both histologically benign and malignant tumors, an infiltrative growth pattern and the risk of local recurrence appear to be the main clinical challenges.^1,7

More uncommon NST subtypes analogous to variants recognized in human medicine have recently been described in cats, including epithelioid-differentiated tumors, ⁸ rhabdomyosarcomatous differentiation (Triton tumor) ⁹ and neuroblastoma-like schwannomas. ¹⁰ NSTs have also been described at anatomically unusual sites, including the tongue, ¹¹ gastrointestinal tract,^6,12 urinary bladder, ¹³ right cerebellopontine angle ¹⁴ and vertebral canal, ¹⁵ the latter causing neurological deficits secondarily to spinal cord compression. However, to the authors’ knowledge, NSTs involving the male reproductive structures in the cat have not been described and are only rarely described in other species.^16,17

Cryptorchidism is a significant reproductive abnormality in male cats, with the retained testes typically located in the inguinal canal or abdominal cavity. ¹⁸ To date, no published reports describe an NST originating within or directly associated with a cryptorchid testis; therefore, this case report describes a new histological type of tumor associated with a cryptorchidic testis.

Case description

An 8-year-old, male domestic shorthair cat, weighing 3.9 kg and from a shelter population, was clinically evaluated for a firm, non-painful, soft tissue mass within the right inguinal region. The oval-shaped mass measured approximately 67 mm × 40 mm on ultrasonography and appeared well-demarcated and heterogeneous, with the appearance of a markedly altered cryptorchid testis. A definitive testicular structure, including a mediastinum testis, could not be identified. No clear extension into the inguinal canal was identified ultrasonographically. Physical examination also revealed the absence of a right scrotal testis; therefore, the mass within the right inguinal canal was presumed to be a cryptorchid testis. The contralateral (left) testis was normally positioned within the scrotum and of normal size and echogenicity. Preoperative hematology and blood biochemistry, as well as thoracic radiographs, were unremarkable.

Oral gabapentin (100 mg) was administered at the shelter before transportation to the clinic for surgery. Premedication consisted of 0.04 ml medetomidine (0.01 mg/kg, Domitor; Orion Pharma) and 0.04 ml butorphanol (0.10 mg/kg IM, Torbugesic; Zoetis), followed by placement of an intravenous catheter in the cephalic vein and deepening of sedation by an additional 0.04 ml medetomidine and 0.04 ml butorphanol intravenously. Abdominal ultrasonography was performed before surgery. No abnormalities were identified in the abdominal organs or regional lymph nodes.

General anesthesia was induced with propofol (approximately 4–6 mg/kg IV to effect, Propoflo 28; Zoetis), endotracheal intubation performed and anesthesia maintained with an isoflurane–oxygen mixture. Lactated Ringer’s solution was provided as intravenous fluid support throughout the procedure (5 ml/kg/h). Perioperative analgesia included buprenorphine (0.02 mg/kg IV, Vetergesic; Ceva) and postoperative meloxicam (0.2 mg/kg, Metacam; Boehringer Ingelheim) administered subcutaneously and continued orally (0.05 mg/kg q24h) after discharge. Cefovecin (8 mg/kg SC, Convenia; Zoetis) was administered perioperatively. Although not routinely recommended as a first-line perioperative antimicrobial, its use in this case was justified owing to the patient’s temperament, which precluded safe oral medication administration, and that he was housed in a shelter environment, with increased risk of wound contamination and an inability to ensure compliance with postoperative oral therapy.

Surgical exploration of the right inguinal region revealed an inguinal cryptorchid testis that was markedly atrophic and enveloped by a pale, firm, irregular and infiltrative neoplastic mass measuring 67 mm × 40 mm × 35 mm. The tunica albuginea and epididymal tissues were conspicuously thickened, and normal testicular architecture was largely inapparent. The neoplastic tissue was excised, with an attempt to obtain wide margins. The inguinal canal, subcutis and skin were closed with a combination of continuous and interrupted sutures using long-term absorbable monofilament material (polydioxanone). A left-sided orchiectomy of the clinically normal testis was performed concurrently. At postoperative re-evaluation, the surgical wounds were healing appropriately, sutures remained intact, and no swelling or recurrent mass was palpable.

Histopathological findings

The whole excised mass, including the testis, was submitted for histopathology. Histologically, the neoplasm was moderately to highly cellular and comprised interlacing fascicles, short bundles and whorls of spindle-shaped cells. Both Antoni A and Antoni B patterns were evident (Figure 1a). Tumor cells had indistinct cell borders, eosinophilic cytoplasm and elongated to ovoid nuclei with coarse chromatin and prominent nucleoli, consistent with NST (Figure 1b). Mitotic activity was moderate, with 14 mitoses seen in 10 HPF (400×; 2.37 mm²), indicative of a malignant form of NST. Foci of hemorrhage, multifocal perivascular lymphocytic infiltrates, nuclear palisading and sclerotic collagenous cores were also present. The neoplasm infiltrated the epididymal structures (Figure 1c and 2a) and extended around the tunica albuginea of the testis, which was composed of severely atrophic seminiferous tubules that contained only Sertoli cells. Numerous interstitial (Leydig) cells were seen, consistent with chronic cryptorchid testicular atrophy. Neoplastic tissue extended to the surgical margins, indicating incomplete excision.

Figure 1.

Microscopic appearance of the neoplasm: (a) the neoplasm was highly (Antoni A) to sparsely (Antoni B) cellular and comprised interlacing fascicles, short bundles and whorls of spindle-shaped cells. Hematoxylin and eosin (H&E) stain, bar = 100 µm; (b) a high-power view of an area of moderately to highly cellular tissues comprising spindle-shaped cells, with elongated to ovoid nuclei, arranged in interlacing fascicles, short bundles and occasional whorls. Occasional mitotic figures (arrows) are apparent. H&E stain, bar = 30 µm; (c) a low-power view with tumor tissues (arrow) infiltrating into and partly separating epididymal ductules (*). H&E stain, bar = 100 µm

Immunohistochemical evaluation of the neoplastic tissue revealed strong cytoplasmic labeling for the mesenchymal cell marker vimentin (dilution 1:400, monoclonal mouse anti-vimentin, clone V9; Dako/Agilent) (Figure 2b) together with diffuse cytoplasmic and nuclear positive labeling for S-100 protein (dilution 1:2000, polyclonal rabbit anti-S100; Dako/Agilent) (Figure 2c). Glial fibrillary acidic protein (GFAP; dilution 1:1000, polyclonal rabbit anti-GFAP; Dako/Agilent) (Figure 2d) immunoreactivity was absent. Overall, the immunohistochemical labeling pattern was supportive of the histopathological diagnosis of NST. The main differential diagnosis given the S-100 positivity was amelanotic spindle cell melanoma; however, the arrangement of neoplastic cells did not support the diagnosis of melanoma. Other differential diagnoses, such as fibrosarcoma or spindle-cell sarcoma, not otherwise specified, were less likely due to the strong S-100 immunoreactivity, which is not a feature of those tumors.

Figure 2.

Immunohistochemical labeling of the neoplastic cells: (a) neoplastic tissue infiltrating the epididymis. Hematoxylin and eosin (H&E) stain, bar = 100 µm; (b) tumor cells demonstrating strong positive cytoplasmic labelling for the mesenchymal cell marker vimentin. Hematoxylin counter stain, bar = 100 µm; (c) tumor cells demonstrating strong positive cytoplasmic and nuclear labelling for S-100. Hematoxylin counter stain, bar = 100 µm; (d) tumor cells are negative staining for glial fibrillary acidic protein.Hematoxylin counter stain, bar = 100 µm

Follow-up information was limited. The cat was reported to be alive and well at the time of the last telephone contact (3 months postoperatively); however, no re-examination or imaging was performed, and the recurrence status remains unknown because of handling limitations and a lack of follow-up visits.

Discussion

NSTs represent an important subset of feline STS and exhibit variable biological behavior. ¹ They typically arise in the skin and subcutis, often affecting the head, limbs and trunk;^{1 –3} however, they have also been described in smaller numbers within the oral cavity,^1,11 elsewhere in the gastrointestinal tract,^6,12 the urinary bladder ¹³ and nervous system.^14,15 Based on the histological findings, MNST in this case most likely originated from peripheral nerve elements within the spermatic cord or peri-testicular soft tissues, with secondary extension around and into adjacent reproductive structures. There is no definitive histological evidence to support a primary intratesticular origin.

Since classification of STSs into the different histological subtypes remains challenging because of overlapping histological features, ⁴ immunohistochemistry is an important component in the diagnosis of NSTs. In the study by Schulman et al, ¹ all NSTs expressed S-100 and vimentin, while GFAP expression was variable, occurring in approximately three-quarters of cases. GFAP negativity was particularly associated with NSTs lacking Antoni A areas or exhibiting neurofibromatous architecture. Thus, the immunophenotype in this present case (S-100 positive, vimentin positive, GFAP negative) aligns with established diagnostic patterns for NSTs, with comparable immunolabeling profiles reported in the two lingual NSTs ¹¹ and in a neuroblastoma-like schwannoma. ¹⁰

STSs in cats display a spectrum of biological behaviors, with prognosis influenced in part by mitotic activity, necrosis and inflammation seen within the tumor. ⁷ Metastasis appears rare,^5,6 and therefore complete surgical excision for local disease control is the critical factor influencing the clinical outcome in most cases.^1,7 However, infiltrative behavior often limits the ability to achieve wide excision, contributing to the potential for local recurrence – a problem documented across feline STSs. ¹¹ In this case, complete surgical excision could not be confirmed at histological assessment, with evidence of neoplastic tissue seen at the apparent margins, meaning that there is a risk of local recurrence at the surgical site.

Although it is known that cryptorchidism increases the risk of testicular neoplasia in species such as humans ¹⁹ and dogs, ²⁰ it is less clear whether (and if so, how) cryptorchidism directly causes the development of such tumors. ²¹ One hypothesis is that the resulting increase in temperature in an abnormally located testis may impact the maturation of testicular cells and predispose them to neoplastic transformation. Alternatively, there may be genetic and/or environmental factors that contribute to both conditions separately but concurrently.^{19 –21}

In the current case, there is a further potential contributing factor; chronic inflammation and persistent tissue irritation are well-recognized drivers of the development of sarcomas in cats.^22–28

In a recent study, inguinal testes accounted for more than half (35/50 cryptorchid cats) of retained gonads in cryptorchid cats. ¹⁸ Although direct causation cannot be definitively established in this case, the chronic mechanical irritation, trauma and low-grade chronic inflammation may have contributed to the development of the NST in this cat. NSTs may potentially originate wherever peripheral nerve elements are found, demonstrated in this case by a tumor arising from nerve structures within or adjacent to reproductive tissues, which have undergone neoplastic transformation.

This report describes a single case, which limits broader conclusions regarding the biological behavior and origin of this tumor. Although the neoplasm infiltrated epididymal structures, a definitive primary intratesticular origin could not be confirmed. In addition, follow-up was limited, and no re-examination or imaging was performed, preventing assessment of recurrence or metastasis. Finally, the proposed role of cryptorchid-associated irritation in tumor development remains speculative.

Conclusions

This case represents the first documented malignant NST infiltrating the epididymis of an inguinal cryptorchid testis in a domestic cat, expanding the recognized anatomical locations for NSTs in this species. Additional cases and further study may clarify the role of mechanical microenvironmental factors in NST development in cats. These findings also underscore the importance of considering NST in the differential diagnosis of inguinal or peri-testicular masses, particularly in non-descended testicles.