Virchow's node, jaundice, and weight loss—lymphoma mimicking gastrointestinal malignancy
Constantinos P Anastassiades* and Thomas H Poterucha About the authors
Correspondence *Department of Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA
Email anastassiades.constantinos@mayo.edu
Summary
Background A 46-year-old white male with a history of well-controlled paranoid schizophrenia presented with painless jaundice, progressive anorexia, weight loss, and dyspnea of 3 months' duration. His only medication at presentation was the antipsychotic olanzapine, taken orally.
Investigations Physical examination and laboratory tests, including a complete blood cell count, electrolyte, lactate dehydrogenase and haptoglobin levels, liver function tests, and a Coombs' test; CT scan of the chest and abdomen; invasive investigations, including thoracentesis and pleural fluid analysis, bone-marrow biopsy, and left supraclavicular lymph-node biopsy.
Diagnosis Diffuse large B-cell lymphoma.
Management Large-volume thoracentesis. Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone chemotherapy followed by dexamethasone, cytarabine, and cisplatin chemotherapy, and autologous stem-cell transplantation.
Keywords:
The case
A 46-year-old white male, with a medical history of paranoid schizophrenia, presented to our clinic in July 2005 with a 3-month history of progressive dyspnea, painless jaundice, weight loss, and anorexia. Most of the patient's history was provided by his mother, who had last seen her son 3 months previously, when he was well. The patient was unaware of the jaundice. He quantified his weight loss as 20 lbs (
9 kg) in 3 months. Furthermore, the patient noted some abdominal distension and bilateral leg swelling. He denied abdominal pain or pruritus, and his bowel habits were unchanged. His stool and urine were normal in color. He had no fevers, rigors, or night sweats. He had neither chest pain nor other respiratory symptoms, and did not have any major risk factors for liver disease.
The patient's past medical history was significant for well-controlled paranoid schizophrenia and secondary hypogonadism. A colonoscopy in 2003 was normal. His only medication was the antipsychotic olanzapine, 7.5 mg taken orally once daily, and he did not use any over-the-counter medications. He had no known allergies and was a nonsmoker. His father had died of leukemia.
On physical examination, the patient was afebrile, his pulse was 130 beats per min and regular, his blood pressure was 102/60 mmHg, his respiratory rate was 30 breaths per min, and his oxygen saturation was 95% on room air. He looked unwell, with dyspnea at rest, and his sclerae were icteric. He had a palpable lymph node in the left supraclavicular fossa (known as a Virchow's node). A pulmonary examination demonstrated decreased breath sounds bilaterally in the lower lung fields, with dullness to percussion. His abdomen was distended, but soft and nontender, with no organomegaly or ascites. A rectal examination was unremarkable. Bilateral pitting edema extending up to his knees was noted.
Initial laboratory results revealed microcytic anemia, with a hemoglobin concentration of 7.1 g/dl, leukocytosis, and thrombocytosis. His bilirubin and liver enzyme levels were elevated, consistent with a cholestatic picture; his total bilirubin level was 1.9 mg/dl (normal range 0.1–1.0 mg/dl), direct bilirubin level 1.2 mg/dl (normal range 0.0–0.3 mg/dl), aspartate aminotransferase level 140 U/l (normal range 12–31 U/l), alanine aminotransferase level 91 U/l (normal range 10–45 U/l), and alkaline phosphatase level 384 U/l (normal range 45–115 U/l). Ferritin, lactate dehydrogenase (LDH), and haptoglobin levels were also high; his ferritin level was 1,716 
g/l (normal range 20–300 g/l), LDH 517 U/l (normal range for adults: 122–222 U/l), and haptoglobin 844 mg/dl (normal range 30–200 mg/dl).
CT scan of the chest revealed large, bilateral pleural effusions with adenopathy (Figure 1), and CT scan of the abdomen (Figure 2) showed multiple splenic masses and extensive bulky lymphadenopathy, including involvement of the porta hepatis. A total of 2,200 cm3 of pleural fluid was aspirated by thoracentesis, which alleviated the patient's respiratory symptoms. The pleural fluid was exudative with atypical lymphoid cells seen on cytologic examination (Figure 3). An incisional left supraclavicular lymph-node biopsy was performed and the sample was submitted for immunoperoxidase studies on paraffin sections with antibodies against several antigens. The tumor cells were positive for CD20 and CD45 antigens and negative for CD3, CD15, CD30, and fascin antigens. These findings supported the diagnosis of malignant lymphoma of B-cell phenotype. Bilateral bone-marrow biopsies were also performed to complete staging, and these showed no lymphomatous involvement of the bone marrow. The final diagnosis was stage IV B diffuse large B-cell lymphoma. The patient was then transferred to the hematology service to receive rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP) chemotherapy. He showed a good, yet partial, response to six cycles of R-CHOP chemotherapy. The hematology service recommended proceeding to autologous stem-cell transplantation because of persistent splenic involvement and because the patient was at high risk for a poor outcome, according to the International Prognostic Factor Index at the time of diagnosis. Before transplantation, the patient underwent two cycles of salvage chemotherapy with dexamethasone, cytarabine, and cisplatin (DHAP) with further partial response. He eventually underwent successful autologous stem-cell transplantation in January 2006. He is currently undergoing 3-month surveillance at the hematology clinic to monitor for disease recurrence.
Figure 1 CT scan of the chest of a 46-year-old white male who presented with painless jaundice, progressive anorexia, and weight loss.
The image shows bilateral large pleural effusions with mediastinal, paratracheal, and subcarinal lymphadenopathy.
Full figure and legend (13K)Figures & Tables indexDownload Power Point slide (62K)Figure 2 CT scan of the abdomen of a 46-year-old white male who presented with painless jaundice, progressive anorexia, and weight loss.
The image shows bulky retroperitoneal and periaortic lymphadenopathy, lymphadenopathy in the porta hepatis, and numerous large heterogeneous splenic masses with splenic enlargement.
Full figure and legend (12K)Figures & Tables indexDownload Power Point slide (60K)Figure 3 Pleural fluid cytology of a 46-year-old man with Virchow's node, painless jaundice, and weight loss, which shows atypical lymphoid cells suspicious for malignancy.
Full figure and legend (3K)Figures & Tables indexDownload Power Point slide (51K)
Discussion of diagnosis and differential diagnosis
Painless jaundice
Painless jaundice in the setting of constitutional symptoms such as anorexia and weight loss is very often suggestive of carcinoma of the head of the pancreas or the ampulla of Vater, because of obstruction of the common bile duct. Physical examination sometimes reveals the Courvoisier's sign (palpable gallbladder). A classic skin manifestation is the Trousseau's phenomenon, also known as thrombophlebitis migrans, which describes venous thrombosis of the upper and lower extremities associated with pancreatic and other visceral malignancies, particularly adenocarcinomas. The 5-year survival rate of pancreatic cancer is poor at 2%.
Jaundice might also be a feature of gastric malignancy. Most patients with carcinoma of the stomach have advanced disease at the time of presentation. Patients with gastric cancer can present with abdominal metastases, which can cause distension (because of ascites) or jaundice (because of liver involvement). Metastases also occur in the bone, brain, and lungs. Weight loss is often the only presenting feature of gastric cancer, although a significant proportion of patients will have a palpable epigastric mass with abdominal tenderness. A Virchow's node is sometimes found. Skin manifestations of gastric malignancy include dermatomyositis and acanthosis nigricans. The overall 5-year survival rate for patients with gastric cancer is 10%, although the 5-year survival rate after surgery for Japanese patients with early-stage gastric cancer is much higher.1
In this patient, gastrointestinal malignancy was initially a major concern. A CT scan of the abdomen was, therefore, one of the initial diagnostic studies performed to look for pancreatic or other intra-abdominal malignancy involving the head of the pancreas, compressing the common bile duct, invading the ampulla of Vater, or metastasizing to the liver.
On review of the literature, the spectrum of diseases that cause painless jaundice, other than pancreatic cancer, seems to be limited. Hodgkin's lymphoma,2 large-cell lymphoma,3 T-cell lymphoma,4 Burkitt's lymphoma,5 extramedullary plasmacytoma of the pancreas,6 and drug-induced hepatitis7 have been described in case reports as the pathologies underlying different presentations of painless jaundice.
Jaundice in patients with lymphoma
Jaundice is a rare presentation of lymphoma. In Hodgkin's lymphoma, less than 15% of cases present with jaundice and the initial manifestation of Hodgkin's lymphoma as a hepatic illness is rare.2 In autopsy series, the incidence of liver involvement in non-Hodgkin's lymphoma (NHL) is about the same as that in Hodgkin's lymphoma.2
Jaundice in patients with lymphoma can be caused by direct liver involvement or extrahepatic obstruction, or a combination of the two. Jaundice can also be 'idiopathic' in up to 25% of cases.2 Histology in idiopathic jaundice reveals intrahepatic cholestasis, without evidence of tumor involvement or hepatic obstruction.8 The mechanism is thought to be defective bile transport across the canalicular membrane.
The left supraclavicular lymph node in metastatic malignancy
A Virchow's node should always alert physicians to the possibility of gastric cancer. A left supraclavicular lymph node might also be involved by other metastatic malignancies, however, including those of abdominal or pelvic origin. A retrospective review of 152 fine-needle aspiration (FNA) biopsies, 87 taken from left supraclavicular lymph nodes and 65 from right supraclavicular lymph nodes, showed that 60% of lymph nodes found positive for malignancy were left nodes and 40% were right nodes.9 In this study, 84% of pelvic tumors and 100% of abdominal malignancies metastasized to the left supraclavicular lymph node. Thorax, breast, head, and neck malignancies showed no differences in metastatic patterns to right and left supraclavicular lymph nodes. Of the patients with lymph nodes found positive for malignancy, 10% had a diagnosis of NHL, leukemia, or Hodgkin's lymphoma.9
It was evident from this study that the primary site and types of malignancy that involved the left supraclavicular lymph node were different from those involving the right lymph node; malignancies originating in the pelvis or abdomen are markedly more likely to metastasize to the left supraclavicular lymph node.
Diffuse large B-cell lymphoma
With regard to this patient's underlying pathology, large B-cell lymphoma is a clinically aggressive NHL, and is the most common histologic subtype,10 constituting approximately 30% of all NHLs. Patients with NHL are generally middle-aged or older at the time of diagnosis, the median age being 64 years.11 They typically present with a rapidly enlarging symptomatic mass, often in the neck or abdomen, which is usually caused by nodal enlargement. The case patient had a neck mass, but was unusually young to present with NHL. Disseminated disease (stage IV) is seen in approximately 40% of patients and is usually defined by extranodal, extramedullary infiltration.12 Systemic 'B' symptoms—fever, weight loss, drenching night sweats—occur in approximately 30% of patients with NHL.10 Based on these characteristics, our patient had stage IV B disease.
Serum LDH levels are elevated in over 50% of patients with systemic B symptoms.10 A high LDH level in patients with lymphoma is a prognostic factor and reflects tumor bulk rather than hemolysis. This patient had a high LDH level and increased indirect and direct bilirubin levels, but no other evidence of hemolysis based on the absence of reticulocytosis, a high haptoglobin level, and a negative Coomb's test. His high LDH level was one of the poor prognostic indicators that led to the recommendation for autologous stem-cell transplantation.
Treatment and management
Current practice in the therapy of advanced-stage NHL involves combination chemotherapy with R-CHOP.13 This patient showed partial response to this regimen. After two cycles of salvage chemotherapy with DHAP, he finally underwent successful autologous stem-cell transplantation 5 months after diagnosis, from which he is currently recovering.
Conclusion
A Virchow's node on physical examination should always alert physicians to the possibility of gastric malignancy. An enlarged left supraclavicular lymph node positive for malignancy is most likely to be of abdominal or pelvic origin, but a minority will be due to lymphoma. The presence of palpable lymphadenopathy in the context of constitutional symptoms and other alarm signs should always raise suspicion for lymphoma. Painless jaundice with constitutional symptoms is not always indicative of pancreatic or gastric cancer. Malignant lymphoma can rarely present with jaundice. This case illustrates that malignant lymphoma must be considered in the broader differential diagnosis of disease which seems to be related to gastrointestinal tract cancer. FNA biopsy is an excellent initial procedure in the work-up of an enlarged supraclavicular lymph node. A high LDH level in the presence of hyperbilirubinemia and jaundice does not automatically suggest hemolysis. Simple procedures such as thoracentesis can be both therapeutic and diagnostic, and they should be undertaken first if indicated.
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Competing interests
The authors declared no competing interests.
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