Dedifferentiated liposarcoma of the spermatic cord

Abstract

A man in his 60s presented to an outside hospital with persistent groin pain and a scrotal mass which was thought to be a recurrent hernia. Three months after initial presentation, the patient was found to have dedifferentiated liposarcoma (LPS) of the spermatic cord. LPS of the spermatic cord is a rare entity; however, clinicians should have LPS on the differential diagnosis especially in men with recurrent scrotal pain and mass. If unrecognised, LPS is associated with a high degree of morbidity and mortality. LPS can be subdivided into well-differentiated LPS, dedifferentiated LPS, myxoid LPS and pleomorphic LPS. In patients with advanced or metastatic LPS, chemotherapy consisting of Adriamycin, ifosfamide and mesna is used despite LPS being relatively chemoresistant. Therapies inhibiting mouse double minute 2 homologue, an oncoprotein that is a negative regulator of the tumour suppressor p53, appear to be promising in preclinical trials.

Background

Liposarcoma (LPS) is a malignant tumour derived from mesodermal embryonic tissue (figure 1). LPS is divided into four subtypes: well-differentiated LPS, dedifferentiated LPS, myxoid LPS and pleomorphic LPS.¹ Well-differentiated LPS is the most common subtype (40–60%) and has little to no metastatic potential. Dedifferentiated LPS represents 15–20% of LPS and metastasis to the lung occurs in approximately 20–30% of cases.¹ Regardless of subtype, treatment involves wide surgical resection of the lesion with adjuvant radiation therapy to reduce risk of local recurrence.²

Figure 1.

Cremasteric Muscle, 2. Adipose and Connective Tissue, 3. Cremasteric Artery and Vein, 4. Vas Deferens, 5. Artery and Vein of Vas Deferens, 6. Testicular Artery, 7. Pampiniform Plexus. Sarcoma is a tumor that is of mesenchymal origin. Liposarcoma of the spermatic cord arises from the adipose tissue within the cord (2). Leiomyosarcoma and rhabdomyosarcoma are other uncommon tumors that may arise in the spermatic cord that comes from the undifferentiated mesenchymal cells of the cremaster muscle (1) and vas deferens (4).

Case presentation

A man in his 60s presented with right groin pain and a palpable, right scrotal mass. The patient had a remote history of an inguinal hernia repair in the 1980s. Three months prior to presentation at our institution, he was thought to have a recurrent right inguinal hernia, so he underwent bilateral laparoscopic transabdominal preperitoneal hernia repair. After the surgery, the patient continued to experience right groin pain with persistence of the scrotal mass thought to represent postoperative seroma versus haematoma. The patient then presented to our institution where ultrasound revealed the mass to be solid. A second surgery was performed to visualise the mass which revealed an irregular soft tissue mass associated with the right spermatic cord, with concern for invasion into the abdominal wall. A biopsy was taken of the specimen.

Investigations

Routine labs were completed including complete blood count, inflammatory markers and comprehensive metabolic panel which were all were within normal limits. A biopsy of the mass revealed well-differentiated LPS (figures 2 and 3).

Figure 2.

Low Power Image (Plain) showing cross section of the cord (Orange) with a small amount of residual fat and soft tissue (Yellow) and large infiltrative mass (Blue).

Figure 3.

Medium Power Image (Plain) showing a small amount of residual fat and soft tissue (Yellow) and the large infiltrative mass as it grows through muscle, nerve, and normal cord architecture (Blue).

To determine the extent of the malignancy, MRI of the abdomen and pelvis was completed which demonstrated postsurgical changes involving the inguinal canal with a 3.2 cm mass associated with the right spermatic cord but no evidence of metastatic disease (figure 4). The patient’s case was subsequently brought before an interdisciplinary tumour board which planned for a right radical transinguinal orchiectomy with possible abdominal wall reconstruction.

Figure 4.

MRI Pelvis with contrast demonstrating an enhancing, diffusion restricting, right inguinal mass associated with the spermatic cord. Compatible with known sarcoma.

Gross resection of the mass was completed within 75 days of the second surgery with final pathology showing a microscopically positive margin and grade 3, 11 mitoses/10 high-power fields consistent with dedifferentiated LPS. Further staging imaging with postoperative positron emission tomography (PET) showed a left pleural nodule suspicious for solitary metastasis (figure 5).

Figure 5.

PET/CT scan demonstrating a fludeoxyglucose (FDG) avid left pleural nodule concerning for metastatic disease.

Treatment

Given the pathology and imaging results, the patient elected to undergo adjuvant radiation therapy with concurrent chemotherapy. At onset of adjuvant radiation therapy, radiation was directed at his right groin and bed of surgical site. Three-week follow-up with CT of the chest redemonstrated left pleural nodule with rapid growth of the nodule in addition to features concerning for early chest wall invasion (figure 6). During this visit, the patient was noted to be more symptomatic with pleuritic chest pain and dyspnoea requiring palliative home oxygen. Given progression of findings, interventional radiology performed a CT-guided biopsy of the left pleural nodule and chest wall lesion for confirmation of diagnosis. Pathology revealed malignant spindle cells similar to the original specimen collected from the right spermatic cord, with scattered reactivity to calretinin and WT1 immunohistochemistry with focal reactivity to cytokeratins (AE1/AE3 and CAM 5.2) consistent with metastatic dedifferentiated LPS.

Figure 6.

CT Scan demonstrating multilobulated pleural-based lesion along the periphery of the mid left lung which was fludeoxyglucose (FDG) avid on PET/CT.

Despite histological and imaging findings suggestive of metastatic disease, there was concern for mesothelioma considering peripheral nature of lesion, reactivity for calretinin and WT1 and occupational shipyard exposure. Pending further studies of the pleural biopsy, the patient completed radiation therapy and began gemcitabine with therapy tailored to cover both mesothelioma and LPS. Further analysis of the lung biopsy demonstrated amplification of MDM2 and CDK4, confirming metastatic, dedifferentiated LPS. The chemotherapy regimen was subsequently narrowed to doxorubicin (Adriamycin), ifosfamide and mesna (AIM therapy). Surveillance PET scan 1 month after the pleural biopsy revealed an increase in size of the left pleural mass, new nodular uptake in the left pleura, a new left upper lobe nodule and recurrent focal uptake in the right scrotum. The patient continued to experience worsening pleuritic chest pain with new left shoulder pain which necessitated the use of oxycodone and morphine.

Outcome and follow-up

Prior to starting the second cycle of AIM therapy, our patient had begun experiencing some decline in health with worsening weakness, reduced appetite, mouth sores and weight loss. After he experienced an episode of altered mental status during inpatient cycle 2 of AIM chemotherapy and was experiencing persistent anaemia with transfusion dependency, he decided to forego any further chemoradiation in favour of palliative measures and home hospice.

Discussion

LPS is divided into well-differentiated LPS, dedifferentiated LPS, myxoid LPS and pleomorphic LPS. Each can be distinguished histologically and through variable gene expression.

Histologically, well-differentiated LPS resembles adipose with intervening fibrous stroma. By contrast, dedifferentiated LPS demonstrates pleomorphic sarcoma with highly cellular areas typically with an abrupt transition to background well-differentiated LPS.³ Both well-differentiated and dedifferentiated LPS involve amplified segments of 12q14-15, specifically the oncogenes CDK4 and MDM2.^{2 4} Typically, dedifferentiated LPS demonstrates stronger expression of CDK4 and MDM2 when compared with well-differentiated LPS.^{4 5} Additionally, co-amplification of JUN (1p32.2) is implicated in the progression of well-differentiated LPS to dedifferentiated LPS and is associated with worse prognosis.^{6 7}

Treatment of dedifferentiated LPS is wide resection of the primary tumour. Use of perioperative AIM chemotherapy remains controversial because dedifferentiated LPS is relatively chemoresistant.^{8 9} As such, therapies targeting the MDM2 pathway are of increasing interest. Preclinical trials of such drugs have shown promise in reducing cell proliferation; however, early in vivo studies have not yet demonstrated sufficient efficacy.^10–12

As seen with our patient, a correct diagnosis is essential as less differentiated types are much more aggressive with metastatic spread and growth and are chemoresistant. Therefore, time is of the essence to make these diagnoses early while the malignancy is still resectable. While LPS is rare, given the high morbidity and mortality of LPS and urgency of appropriate management, there should be an elevated index of suspicion in investigation of scrotal masses to ensure malignancy is not missed and lead to poor outcomes (figure 7).

Figure 7.

Algorithm for evaluation of scrotal mass based on physical exam and imaging findings.

Learning points.

• Although liposarcoma of the spermatic cord is a rare entity, clinicians should have a high index of suspicion for this pathology in men with recurrent scrotal pain and mass given the high morbidity and mortality associated with liposarcoma.

• Liposarcoma can be divided into well-differentiated liposarcoma, dedifferentiated liposarcoma, myxoid liposarcoma and pleomorphic liposarcoma. Each carries a different prognosis and requires slightly different treatment based on metastatic potential.

• Mainstay liposarcoma treatment remains wide resection±adjuvant radiation therapy. Adriamycin, ifosfamide and mesna chemotherapy is used in patients with advanced or metastatic disease with little success. However, molecular therapies targeting MDM2 have demonstrated promise in reducing cancer cell proliferation in preclinical trials.

Ethics statements

Patient consent for publication

Consent obtained directly from patient(s).