Left supraclavicular (Virchow’s) node metastasis detected before primary infradiaphragmatic tumor: a case series

A 78-year-old Japanese woman with a diagnosis of tongue carcinoma underwent partial glossectomy in May 2002 and ipsilateral neck dissection (levels I–V) in July 2002. The pathological diagnosis was poorly differentiated squamous cell carcinoma (pT1N2bM0, according to the Union for International Cancer Control (UICC) TNM classification, 7th edition). She had no notable medical history at the time of her treatment for tongue carcinoma. We subsequently palpated left-sided supraclavicular lymphadenopathy at a postsurgical follow-up visit in July 2003 (Fig. 1A). Biopsy of the left supraclavicular lymph node yielded a diagnosis of adenocarcinoma (Fig. 2). Her carbohydrate antigen 19-9 (CA19-9) and alpha-fetoprotein levels were elevated to 4100 U/mL and 49.0 ng/dL, respectively. Infiltrative intrahepatic cholangiocarcinoma was detected on whole-body computed tomography (CT) scan (Fig. 1B). The patient consented to additional tissue biopsy of the bile duct, and the clinical diagnosis was cholangiocarcinoma (T2N1M1). She opted for palliative care and died 11 months after detection of left supraclavicular lymph node metastasis.

A 64-year-old Japanese man underwent ipsilateral neck dissection (levels I–III), partial glossectomy, and forearm flap reconstruction for moderately differentiated squamous cell carcinoma of the tongue in February 2007. His medical history at the time when tongue carcinoma was detected included chronic otitis media. The pathological diagnosis was poorly differentiated squamous cell carcinoma (pT2N1M0). He revisited our department in March 2012 after noticing left supraclavicular lymphadenopathy (Fig. 3A). Fine-needle aspiration biopsy of the left supraclavicular lymph node revealed atypical cells with slight squamous differentiation, which was diagnosed as class IV, and biopsy of the left supraclavicular lymph node led to a diagnosis of carcinoma (Fig. 4A). Primary cancer screening was started in the head and neck and lung regions, but during that time, he developed postrenal renal failure (Fig. 3B), and a bladder tumor was found on an enhanced pelvic CT scan (Fig. 3C). Hematoxylin–eosin staining of the bladder lesion did not identify a clear glandular or squamous component, and we could not make a definitive diagnosis of whether the lesion was poorly differentiated squamous cell carcinoma, adenocarcinoma, or high-grade urothelial carcinoma (Fig. 4B). Immunopathological examination of the left supraclavicular lymph node showed CK7(+), CK20(−), and GATA3(+) (Fig. 5A), and the bladder lesion showed CK7(+), CK20(−), and GATA3(+) (Fig. 5B). On the other hand, immunopathological examination of the squamous cell carcinoma on the tongue showed GATA3(−) (Fig. 5C). Based on these pathological findings, the diagnosis was compatible with primary bladder cancer with metastasis to the left supraclavicular lymph node (pT2N2M1). The patient opted for palliative care and died 2 months later.

A 61-year-old Japanese man underwent ipsilateral neck dissection (levels I–III), partial glossectomy, and forearm flap reconstruction for poorly differentiated squamous cell carcinoma on the right side of the tongue in March 2011. His medical history included hypertension and a duodenal ulcer. The pathological diagnosis was poorly differentiated squamous cell carcinoma (pT2N0M0). Follow-up ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (¹⁸F‐FDG‐PET/CT) in March 2013 showed intense ¹⁸F‐FDG accumulation in the left supraclavicular (Fig. 6A) and right obturator (Fig. 6B) lymph nodes. ¹⁸F‐FDG uptake in the prostate was weak (Fig. 6C). Biopsy of the left supraclavicular lymph node gave a diagnosis of adenocarcinoma (Fig. 7A). Contrast-enhanced magnetic resonance imaging (MRI) of the pelvis showed adenopathy of the obturator nodes on the right side of the prostate region and an enhancing lesion in the prostate on contrast-enhanced T1-weighted images (Fig. 6D). Biopsy of the prostate revealed adenocarcinoma with Gleason score of 9 (4 + 5) that was diagnosed as prostate carcinoma (pT2N1M1) (Fig. 7B). His prostate-specific antigen (PSA) level at time of diagnosis was elevated at 123.9 ng/mL. Bilateral orchiectomy and adjuvant hormonal therapy were performed. He died 47 months after diagnosis of left supraclavicular lymph node metastasis.

Combined radiological and serological assessments are useful for the diagnosis of primary cancer. CA19-9 and alpha-fetoprotein levels helped make the diagnosis in our first case, as did the PSA level in the second case. ¹⁸F‐FDG‐PET/CT has greatly improved our ability to detect an unknown primary tumor, particularly at a distant location. However, ¹⁸F-FDG PET/CT sometimes fails to reveal organ-localized prostate cancer [12‐15]. In our third case, the ¹⁸F‐FDG uptake was weak on ¹⁸F-FDG-PET/CT and MRI findings aided the diagnosis. Thus, prostate cancer cannot be ruled out even if the uptake is weak, and careful examinations, such as PSA measurements, should be considered.

In our second case, because of the presence of atypical cells with slight squamous differentiation in the fine-needle aspiration biopsy and the lymph node specimen, the difficulty of obtaining a definitive pathological diagnosis from excisional biopsy of the left supraclavicular lymph node, and the patient’s history of squamous cell carcinoma of the tongue, primary cancer screening was started in the head and neck and lung regions. However, the lymph node metastasis originated from the bladder. The histological presentation of urothelial carcinoma is very similar to that of squamous cell carcinoma [11, 16, 17]. If histopathological examination reveals squamous differentiation in metastatic cervical lymph nodes, it is necessary to include the bladder in the search for the primary cancer site [16, 18]. In this case, GATA3(+) staining of the metastasis to the supraclavicular lymph node revealed that the primary cancer was not squamous cell carcinoma of the tongue but urothelial carcinoma in the bladder. The CK7(+) and CK20(−) phenotypes indicate a high probability of bladder urothelial carcinoma [19]. Combined immunolabeling for CK7 and CK20 often aids in the identification of urothelial bladder cancer; however, these markers have limited sensitivity and specificity [19]. Immunohistochemistry of the transcription factor GATA3, a sensitive and specific diagnostic urinary epithelial marker, has been widely used in the diagnosis of urothelial cancer [19, 20].

Our first patient opted for palliative care only and survived for 11 months after diagnosis of lymph node metastasis. There have been some reports of improved survival (for more than 6 years) after successful chemotherapy treatment for metastasis of cholangiocarcinoma to Virchow’s node [21, 22]. Therefore, the prognosis of patients with intrahepatic cholangiocarcinoma and metastasis to the left supraclavicular lymph node is not always poor [21].

The prognosis has been consistently poor in the limited number of case reports on cervical lymph node metastasis from bladder carcinoma [23, 24]. The median survival of patients with metastatic bladder cancer who receive supportive care alone is 4–6 months [18]. Our second patient, who chose palliative care, survived for only 2 months after diagnosis of left supraclavicular lymph node metastasis. As in previous reports, his prognosis was poor.

Even for patients with advanced-stage prostate adenocarcinoma and metastasis to the head and neck region, survival may be extended by rapid diagnosis and appropriate treatment [25]. Hormonal therapy has been shown to prolong survival, even for patients with metastasis of prostate adenocarcinoma to Virchow’s node [26]. One study found that the average survival time was 25.8 (range 1–101) months for patients with prostate adenocarcinoma and Virchow’s node metastasis and pointed out that the prognosis of these patients was superior to that of patients with metastatic adenocarcinoma of nonprostatic origin [25]. Our third patient survived for 47 months after diagnosis of left supraclavicular lymph node metastasis.

The prognosis of malignant infradiaphragmatic tumors after metastasis to Virchow’s node is generally considered to be extremely poor [21]. However, our experience suggests that the prognosis may depend on the characteristics of the tumor and that rapid diagnosis is important for providing appropriate treatment. Enlarged left supraclavicular lymph nodes can be more easily palpated and visually inspected than nodes in other areas of the body. If enlarged left supraclavicular lymph nodes are detected on routine clinical examination, clinicians should request additional assessments such as CT, MRI, ultrasonography, and PET/CT to ensure rapid detection and diagnosis of the primary lesion. In addition, biopsy of the enlarged cervical lymph nodes and serological assessments should be conducted to diagnose the primary cancer.

Further accumulation of cases and more detailed studies of malignant infradiaphragmatic tumors with Virchow’s node metastasis are needed.