Supraclavicular left neck mass: an unusual presentation of metastatic testicular cancer in two older men

Abstract

Two male patients, aged 55 and 75 years, were referred to the ENT and haematology team respectively, with an asymptomatic left supraclavicular neck mass. Investigations revealed metastatic primary testicular seminoma. CT contrast study of the thorax, abdomen and pelvis demonstrated an additional left para-aortic nodal mass in both cases. The initial presentation of a solitary left neck lump from a metastatic testicular seminoma is extremely unusual, especially in an older age group. The pattern of metastatic spread to the supraclavicular neck nodes from a single para-aortic lymph node is also an interesting finding. Although the majority of seminomas present in younger patients in the early stages when confined to the testis, seminoma can also occur in older patients and can present in an atypical manner. The ability to recognise an atypical presentation in an older patient is invaluable for prompt diagnosis, treatment and follow-up of disease. This case also highlights the importance of a multisystematic structured and an open-minded approach to investigating and diagnosing a neck mass.

Background

Testicular germ cell tumours (GCTs) account for approximately 1% of cancers in the male population and are also the most common solid cancer in men aged 15–34 years.¹ Historically, testicular GCTs were subdivided into seminoma and non-seminomatous germ cell tumour (NSGCT); however, in the more recent edition of the WHO classification (2016), GCT classification is reconstructed into tumours derived from germ cell neoplasia in situ and those not derived from germ cell neoplasia in situ; seminoma falls into the former subgroup.²

The peak incidence for seminoma is 34–45 years with the peak age of diagnosis being 34 years.³ There is a paucity of literature describing seminoma patterns of disease in the older population, although there is evidence of increasing age at the time of presentation with GCTs over the last decade.⁴

Neck mass is a common presentation in GP and ENT clinics, and the differential diagnosis is wide, including infection, inflammatory, congenital and neoplastic disease. Initial presentation of a malignant testicular tumour with a neck lump is unusual as the most common presentation for a germ cell testicular cancer is a painless testicular enlargement.^5–7 Among patients with testicular cancer, the incidence of neck nodal metastases is between 4.5% and 15% and only 5% of these have a neck mass as the initial presenting sign.¹ This case report focuses on two patients with metastatic seminoma who presented unusually but also similarly.

Case presentation

Case 1

A usually fit and well 55-year-old man (patient 1) presented to his general practitioner (GP) with a 5-week history of sudden onset and rapidly enlarging left neck mass with no associated symptoms or other clinical findings. He had a surgical history of vasectomy in 2002 and was taking no medications. He was referred to ENT for suspected laryngeal malignancy. He had no symptoms of lymphoma (night sweats, weight loss or fever) or symptoms of upper aerodigestive tract malignancy such as dysphagia, sore throat or change in voice. Fibreoptic nasendoscopy was unremarkable. On examination, he had a large, firm, non-tender level 5 neck mass.

The patient did not have any testicular symptoms, and clinical examination did not reveal any suspicious signs for testicular cancer.

Case 2

A usually fit and well 75-year-old man (patient 2) presented to his GP with a 3-week history of left-sided asymptomatic neck mass. He was referred to haematology for suspected non-Hodgkin’s lymphoma. Patient 2 had a surgical history of vasectomy in 2005 and was otherwise well. Clinical examination findings were similar to patient 1. He had a solitary firm non-tender left-sided neck mass. He did not complain of any upper aerodigestive tract malignancy symptoms. The patient did not have any testicular symptoms, and clinical examination did not reveal any suspicious signs for testicular cancer.

Investigations

Case 1

The ENT surgeons arranged an ultrasound of neck with an ultrasound-guided core needle biopsy. A level 5 left neck soft tissue mass was identified; sonographically lymphoma was suspected. Under ultrasound guidance, several core samples were taken with a 14-gauge needle and sent to histology. The thyroid, major salivary glands and right side of the neck were unremarkable.

Due to the suspicion of malignancy, a staging CT contrast study of the neck, thorax, body and pelvis was performed and confirmed a left neck mass consistent with an enlarged lymph node (figure 1) and an associated left para-aortic lymph node (figure 2). No pelvic or urological masses were identified. The liver and lungs were normal and no other enlarged nodes were seen.

Figure 1.

Contrast enhanced CT neck in patient 1. Large soft tissue mass in the root of the left neck at level 5, measuring 42×58 mm in transverse dimensions (arrows). The lesion would be consistent with a significantly enlarged lymph node, which distorts the left internal jugular vein anteriorly and medially.

Figure 2.

Contrast enhanced CT abdomen in patient 1. Single enlarged left para-aortic lymph node (arrows) at the level of renal hila. This was not associated with any other pelvic or para-aortic lymphadenopathy.

Routine blood tests including full blood count, liver function and renal function tests were normal.

Serum human chorionic gonadotropin (hCG) (10.4 iu/L; reference range 0–2 iu/L) and alpha-fetoprotein (AFP) (6.1 ku/L; reference range 0–5.8 ku/L) were raised, while lactate dehydrogenase (LDH) was within normal limits (357 iu/L; reference range 240–480 iu/L).

The core biopsy was consistent with metastatic seminoma with the primary origin of malignancy in either the testis or mediastinum (figure 3).

Figure 3.

Left image: H&E stain low power. Right image placental alkaline phosphatase (PLAP) stain high power. The H&E image shows nests of malignant cells with clear cytoplasm; the tumour cells are strongly positive for PLAP confirming the diagnosis of metastatic seminoma.

Despite no testicular symptoms or suspicious signs found on clinical examination, the core biopsy results prompted an ultrasound of the testes, and features of diffuse testicular tumour were demonstrated in his left testis (figure 4).

Figure 4.

Ultrasound testis of patient 1: the left testis was smaller than the contralateral side with an ill-defined vascularised focus of reduced echogenicity (arrow) and scatter area of microcalcifications; findings consistent with diffuse malignant infiltration.

The patient was discussed at the urology multidisciplinary team meeting (MDM) and was referred for initial chemotherapy and consideration of orchiectomy.

Case 2

Haematology organised an urgent ultrasound of the neck with an ultrasound-guided core biopsy of the left neck mass. Ultrasound of the neck demonstrated a bulky abnormal mass in the root of the left neck, extending into the superior mediastinum. Lymphoma was considered a likely diagnosis and under ultrasound guidance, multiple 14-gauge core samples were taken from the left neck mass and sent to histology. A staging CT contrast study of the neck, chest, abdomen and pelvis confirmed an enlarged level 4 left neck nodal mass measuring 6 cm (figure 5). A bulky left para-aortic lymph node measuring 3.3 cm was also identified (figure 6) with no other site of disease seen.

Figure 5.

Contrast enhanced CT neck in patient 2. Enlarged left level 4 nodal mass (arrows), measuring 6 cm in size.

Figure 6.

Contrast enhanced CT abdomen image in patient 2. Enlarged left para-aortic lymph node (arrow) at the level of renal hila. No associated pelvic or inguinal lymph nodes.

Routine blood tests including full blood count, liver function and renal function tests were normal.

AFP was raised to 7.3 kiu/L (reference 0–5.8 kiu/L). LDH was slightly raised (255 u/L, reference 0–250 u/L), and serum-hCG was within normal limits. The core biopsy was most consistent with metastatic seminoma (figure 7). The testes were the most likely site of origin for his primary tumour, and therefore an ultrasound of the testes was carried out. The findings were consistent with diffuse malignant infiltration in the left testis (figure 8).

Figure 7.

Left image: H&E stain low power. Right image: PLAP stain high power. These images show very similar appearances to those included in figure 3; tumour cells again strongly positive for PLAP. PLAP, placental alkaline phosphatase.

Figure 8.

Ultrasound testis of patient 2. The left testis (8 mL) is smaller than the contralateral side (14 mL) and has diffuse ill-defined areas of reduced echogenicity in keeping with malignant infiltration (arrow).

The patient was discussed at the haematology and urology MDM and referred for initial chemotherapy and consideration for orchiectomy.

Treatment

Typical chemotherapy regimens for seminoma include three cycles of bleomycin, etoposide and cisplatin or four cycles of etoposide and cisplatin (EP).⁸ More serious adverse effects caused by bleomycin toxicity include pneumonitis and pulmonary fibrosis. A predictive factor for the development of such toxicity is advanced age⁹; therefore, both patients in this study were given four cycles of EP instead.

Both patients completed their initial four cycles of chemotherapy (etoposide and cisplatin) and then were both planned to have a delayed radical orchiectomy.

Outcome and follow-up

Both patients were followed up approximately 6 months after their initial presentation to their GP.

On follow-up, both patients demonstrated a good response to their initial chemotherapy treatment and experienced no adverse reactions or complications from it. Follow-up CT chest, abdomen and pelvis scans postchemotherapy demonstrated a significant reduction in the size of their neck and para-aortic lymph nodes. Postchemotherapy blood tumour markers (AFP, serum hCG and LDH) returned to normal limits suggestive of a complete response.

Orchidectomy was performed successfully on case 1, and the histological analysis of the specimens found no necrosis or any residual viable tumour. Case 2 awaits orchidectomy. The management plan after orchidectomy for both patients involves close clinical and imaging/CT surveillance.

Discussion

GCTs, which are divided into NSGCT and seminoma, are the most common solid tumour in young adults; however, they are generally accepted to become less frequent in the older population.⁷ More than 90% GCTs occur in patients less than 50 years of age, fewer than 10% are diagnosed at 50 years and less than 2% at 65 years.^{10 11} The incidence for seminoma and NSGCT differs from their peak age; for seminoma, it is 34–39 years,³ and for NSGCTs, it is 25–29 years.¹⁰ Van Vledder et al reviewed 665 patients with metastatic testicular cancer and found seminoma accounted for 24%, while NSGCTs comprised 76%.¹¹ In other publications, seminoma has been suggested to account for up to 60% of all testicular GCTs making it the most common germ cell subgroup.^{1 10} Currently, seminoma is accepted to outnumber NSGCTs in all major epidemiological reports.¹² In England, the significant relative increase in the number of seminoma over NSGCT was first noted in the 1980s, with a rise from 43% (1983–89) to 58% (1996–2002).¹²

In this case report, we have presented two patients with metastatic testicular seminoma who were diagnosed at an older age compared with the usually recognised age group (55 and 75 years). Further review with more recent literature⁴ suggests that over the last decade there has been an increasing age at presentation for GCTs.⁴ This epidemiological change was reviewed in Germany in 2013, where Ruf et al¹² compared the age distribution of patients’ presenting with testicular cancer between 1976–1990 and 2005–2010. It was found that the mean age rose from 34 years to 39 years in seminoma, and from 26 years to 31 years in NSGCTs (p≤0.001). There is little literature on the clinical characteristics and outcomes in the older population diagnosed with seminoma although this seems to be of increasing importance with the aforementioned epidemiological changes. Some studies have positively correlated patient age with a more advanced stage of disease at the time of diagnosis and less desirable response to treatment, making age an independent negative prognostic factor.¹⁰ The two patients presented in this case both had left supraclavicular lymphadenopathy, classified as stage III advanced disease. They both have demonstrated a good response to their chemotherapy treatment.

Among patients with testicular cancer, the incidence of neck metastases accounts for only a very small proportion of cases (4.5%–15%) overall, and only an estimated 5% of these have a neck mass as the initial presenting sign.¹ Seminomas typically present in the early stages of disease (70%) and remain confined to the testis.¹³ Once cervical nodes are involved, this becomes at least an advanced stage III disease, and the initial treatment is generally chemotherapy.¹ Well-known pathways of metastasis in GCTs include the lymphatic pathway, where the pattern of disease spread tends to be contiguous with the anatomy of the lymphatic’s and the haematogenous pathway, where the disease spreads via the blood to the liver, lung and bones. Understanding the patterns of disease spread is invaluable to a radiologist when staging disease/identifying recurrence of disease. Accurate detection of metastases is important as chemotherapy offers an excellent chance of cure, even at more advanced stages.⁷

Lymphatic pathway

Testicular cancer first spreads to the retroperitoneal lymphatic channels, which converge at L1/2 level. Lymphatics from the right testis drain primarily to areas medial, lateral and anterior to the vena cava and anterior to the aorta. The left testis generally drains into regions medial, lateral and anterior to the abdominal aorta.¹⁴ At the level of T12, the thoracic duct traverses the diaphragm between the descending aorta and azygous vein and extends up to the root of the neck. The thoracic duct remains in the posterior mediastinum in the azygo-oesophageal recess until it reaches T5 (level of the carina) where it crosses to the left side before opening up in the root of neck, at the junction between the left subclavian and internal jugular vein.⁷ Right to left crossover occurs in advanced disease, whereas left to right crossover is rare.⁷ The thoracic duct anatomy would explain why almost exclusively deposits would be present in the left supraclavicular fossa,¹ similar to the two cases presented in this report. Testicular seminoma inclines the lymphatic pathway of metastasis and spread to the head and neck areas are considered rare.^{4 15} If the neck lymph nodes are involved, one would assume the mediastinum nodes usually also to be involved (although not in our cases).

Wood et al⁷ reviewed the clinical and imaging findings of 31 patients with neck nodal metastases from primary testicular GCT, where a minority (11/31) had seminoma and 21/31 had NSGCT. Neck lymphadenopathy was identified in 91% of patients with seminoma and 65% with NSGCT.⁷ The authors noticed that 55% of the seminoma patients who had neck lymphadenopathy also had mediastinum lymphadenopathy (especially subcarinal and para-oesophageal) as opposed to only 10% of NSGCT. This difference was statistically significant (p=0.0124 Fisher’s exact test). The paper also observed that the neck metastases were almost exclusively left sided with 21/23 patients having disease in the left supraclavicular/scalene nodes.⁶ This follows the pattern of lymphatic anatomy.⁷ Forty-five per cent of patients with seminoma had neck lymphadenopathy without mediastinum involvement in Woods’ study, a finding also observed in the two patients included in our paper.

Haematogenous pathway

Another mode of metastasis is via the haematogenous pathway. One possible mechanism involves the metastatic reflux theory via the Batsons paraspinal venous plexus. This is driven by an increase in the intrathoracic/intra-abdominal pressures by activities such as straining. This mechanism permits retroperitoneal renal cell carcinomas to metastasise to the head and neck regions; it may also explain this mode of spread in seminoma.^{1 6} The other histological subtype of GCTs, NSGCT, is known to have a less contiguous spread of disease compared with seminoma. For instance, patients with NSGCTs with neck lymphadenopathy may have no mediastinal lymphadenopathy. This more random pattern of disease may be explained by NSGCTs’ tendency towards the haematogenous pathway of spread.^{4 7}

It has been recognised that both seminoma and NSGCTs arise from a common precursor carcinoma in situ.¹⁵ Fifteen per cent of tumours also demonstrate elements of both seminoma and NSGCT in their primary site and occasionally seminoma can transform into NSGCT.^{7 16 17} It is not surprising that there may be a degree of radiological and/or clinical characteristic overlap between seminoma and NSGCTs.^{7 17}

It could be suggested that seminomas with elements of NSGCTs have an increased tendency and a potential to exhibit a haematological pathway of metastasis, that is, metastasis to the neck and skipping the mediastinal nodes. This may explain the pattern of disease spread in our two patients.

Testicular tumour serum markers

Tumour markers such as AFP, serum hCG and LDH have established roles in the diagnosis, prognosis, treatment and monitoring of patients with testicular cancer. Tumour markers are essentially molecules or substances, which are produced either by the tumour or normal cells in response to the tumour. They can be qualitatively and quantitatively measured in patients’ blood. The pattern of these tumour markers can help differentiate between subtypes of GCTs (eg, NSGCT or seminoma), stage of disease (early or advanced stage) and response to treatment over time.

AFP is a glycoprotein normally produced by the foetal yolk sac, liver and gastrointestinal tract.¹⁸ AFP is undetectable in men normally. The yolk sac tissues regain their ability to produce this oncomarker when they undergo malignant transformation and raised levels are typically found in NSGCTs. Pure seminoma should not by definition produce any AFP, and a raised AFP is considered an atypical feature of seminoma, seen in only 0%–4% of cases.⁷ Elevated serum AFP levels in patients with seminoma are usually interpreted as the tumour containing additional occult elements of NSGCT,¹⁶ and when an elevated serum AFP is seen, patients should potentially be treated as if they had NSGCT.¹⁷

The two patients in this case report have a mildly raised AFP (case 1: 6.1 kiu/L; case 2: 7.3 kiu/L, reference 0–5.8), which as explained above, is not typical in pure seminoma.

It should be noted that the two patients, in this case, were diagnosed from core biopsies taken from their neck mass and histological analysis can only be performed on the samples taken. It is therefore not possible to ascertain there are no other cell types within the entirety of the neck mass, noting also complete tumour response in testis; however, one could surmise that a raised AFP is indicative of potential mixed GCT primary.

Conclusion

Both patients diagnosed with metastatic seminoma in this case report presented in a strikingly similar but also an unusual way, that is, with a neck mass, which occurs in less than 5% of seminoma cases.¹ They also displayed similar radiological and clinicopathological findings, which are considered atypical for pure seminomas. For instance, they both had a raised AFP and a pattern of disease spread (seen on radiological imaging) more consistent with NSGCTs rather than for seminoma. Therefore, it is highly likely their tumour was heterogeneous in nature, and their seminoma has mixed germ cell components within it. Contrary to popular belief, there appears to be an increasing prevalence of seminoma in the older age group. Although the majority of seminoma usually presents in the early stages of the disease and has a contiguous pattern of metastasis, both patients in this case presented with advanced disease and a pattern of metastasis with features of NSGCTs rather than pure seminoma.

It is suggested that seminoma with mixed germ cell lineages may present in an unusual way and occur in an older age group of men. They may demonstrate atypical patterns of disease spread on radiological imaging and a mildly raised AFP from biochemical analyses. This is important to recognise as mixed seminoma generally has a worse prognosis compared with pure seminoma and risk stratification and management may differ accordingly.¹⁹ Recognising the pattern of disease spread is also important to a radiologist as it helps them focus on particular locations when assessing disease stage and suspected recurrence.

The differential diagnosis for a neck mass is wide; it is unusual for this to be the initial presentation for metastatic seminoma. When seminomas have mixed germ cell components, there is a potential for these tumours to present in a more atypical way as in these two patient cases.

One should consider metastatic seminoma as a working differential diagnosis in men (including older men) who present with an asymptomatic neck mass. With an ageing population in mind and with increasing age at presentation for testicular cancer,⁴ more awareness of metastatic seminoma as a differential diagnosis for a neck mass is important in both primary and tertiary clinical settings. It is also stressed that the two patients included in this case did not have a palpable testicular lump or testicular pain on examination. Therefore, this highlights the necessity for an open-minded multisystematic approach, and in some cases even when the clinical examination of the testes may be normal one should still keep metastatic testicular seminoma in mind and appropriate imaging investigations such as ultrasound of the testes may still be invaluable.

Learning points.

• Testicular tumour can present in older males, neck mass, although rare, maybe a presenting sign, particularly in mixed germ cell tumour subtypes.

• A multisystematic approach when consulting patients presenting with an asymptomatic neck mass should be offered, and even if the clinical examination of the testes is normal, an ultrasound of the testes can still be considered.

• Seminoma with atypical features suggestive of mixed germ cell types should be recognised promptly as their prognosis is worse than that for pure seminoma and this change prognostic stratification and patient management. If there are overlaps between the radiological and clinicopathological patterns of seminoma and non-seminomatous germ cell tumour, one should be prompted to suspect heterogeneity of the primary tumour.