Renal Cell Carcinoma With Intravascular Lymphomatosis: A Case Report of Unusual Collision Tumors With Review of the Literature

Intravascular lymphomatosis (IVL) is a rare entity reported initially by Pfleger and Tappeiner in 1959.1 It is a variant of aggressive non-Hodgkin lymphoma characterized by a peculiar intravascular proliferation of morphologically neoplastic lymphoid cells. Many terms have been used in the past to describe IVL, including angioendotheliomatosis proliferans systematica and angiotropic large cell lymphoma.1,2 However, most authors prefer the more descriptive term IVL.3,4 The majority of IVL cases are of B-cell phenotype, as demonstrated by immunohistochemical,3,4 Southern blot, and gene rearrangement studies.5 

Intravascular lymphomatosis typically presents as a primary intravascular neoplasm without a solitary component; however, it rarely can result from a disseminated lymphoma.6,7 Intravascular lymphomatosis has been associated with involvement of multiple organs, including the spleen, kidney, lung, endocrine organs, and heart.2,8 The central nervous system and skin, however, are by far the most common sites of involvement, occurring in 32% and 47% of cases, respectively.2 Lymph node and bone marrow involvement, in contrast, are distinctly uncommon.

Previous case reports have described systemic IVL coexisting with other primary neoplasms, such as hemangioma6; however, to our knowledge the literature includes no description of renal cell carcinoma (RCC) containing IVL.

This case report describes a subcutaneous lymphoma of the breast with disseminated IVL. The latter was identified within a conventional RCC. This is a rare and unique entity of collision tumors of RCC coexisting with IVL.

A 77-year-old woman was admitted to Mount Sinai Hospital of Queens, NY, with complaints of weakness, lethargy, dizziness, and weight loss for more than 1 year. One week prior to admission, she had an episode of nausea and vomiting, which resolved spontaneously. She had been previously healthy and denied any past medical or surgical history.

Physical examination revealed a thin, elderly white woman. There were no significant abnormal physical findings other than a mobile breast nodule located in the upper outer quadrant of the left breast. No adenopathy was noted.

Laboratory tests revealed increased levels of lactase dehydrogenase (1254 U/L, reference range, 94–250 U/L), alkaline phosphatase (132 U/L, reference range, 39–117 U/L), and serum urea nitrogen (15 mmol/L, reference range, 3.6–4 mmol/L). All remaining electrolyte levels and liver function tests were within normal limits. Chest computed tomographic scan showed a left breast nodule, but was without evidence of metastases. Abdominal and pelvic computed tomography revealed a 9.5-cm mass in the upper pole of the right kidney (Figure, A) with no adenopathy. Chest radiographs and bone scan were negative for metastases. Subsequently, the patient underwent an excisional biopsy of the left breast mass and a simultaneous right radical nephrectomy. A subsequent bone marrow biopsy was negative for malignancy or infiltrative disease. The patient did well postoperatively, and chemotherapy consisting of cyclophosphamide, vincristine, adriamycin, and prednisone was initiated.

Six months following surgery, the patient died of pneumonia. No autopsy was performed.

The surgical specimens were fixed in a 10% buffered formalin solution and processed for paraffin-embedded blocks. All sections were stained with hematoxylin-eosin.

Immunological markers were performed on paraffin sections of the breast and kidney lesions, using a standard avidin-biotin complex method with diaminobenzidine. Antibodies included cytokeratin (CAM 5.2, 1:4; Becton Dickinson, San Diego, Calif), leukocyte common antigen (CD45, 1:40), L26 (CD20, 1:400), UCHL-1 (CD45RO, 1:200), and CD79a (1:50) (Dako Corporation, Carpinteria, Calif).

The biopsy of the left breast consisted of an ellipse of lightly pigmented skin and underlying subcutaneous tissue measuring 4.2 × 1.6 × 2.8 cm. The skin surface was unremarkable; however, there was a palpable nodule beneath the epidermis. Cross sections revealed a well-demarcated, ovoid, tan, fish-flesh tumor with central necrosis, measuring 3.0 × 1.6 × 1.6 cm and involving the dermis and subcutis. Also received at the same time was a right total nephrectomy and attached portion of adrenal gland. The kidney was markedly enlarged, measuring 13 × 11 × 10 cm and weighing 364 g. At the upper pole, there was a partially cystic tumor mass measuring 9.5 × 7 × 7 cm. The tumor appeared tan-gold with extensive areas of necrosis. The renal capsule, ureter, renal veins, and adrenal gland were free of tumor. In addition, there was a 1.2-cm, orange-brown calculus present in the renal pelvis.

The sections of the left breast nodule demonstrated a diffuse large cell lymphoma involving skin and subcutaneous tissue. No breast elements were seen. The right nephrectomy specimen exhibited an RCC (clear cell type, nuclear grade II) with extensive IVL (Figure, B and C). The RCC extended into but not entirely through the renal capsule. All the resection margins were free of tumor.

The tumor cells in the breast skin lesion and the intravascular tumor cells in the RCC demonstrated an identical B-cell phenotype (CD20⁺, CD79a⁺, CD45⁺, CD3⁻, UCHL-1⁻, and CD30⁻) (Figure, D). The findings were consistent with malignant lymphoma, diffuse large B-cell type (REAL classification: diffuse large B-cell lymphoma with intravascular lymphomatosis).

Intravascular lymphomatosis usually presents as a primary intravascular neoplasm without known primary lymphoma, although it may also occur as a manifestation of disseminated disease.3,4,6,7 Intravascular lymphomatosis was originally believed to be a malignant proliferation of endothelial cells; however, further studies, including immunohistochemistry, Southern blot analysis, and polymerase chain reaction gene rearrangement, have identified a B-cell lineage in the majority of cases.3,5 

The most common presentations of IVL are fever of unknown origin, change in mental status, and skin rash; however, other organs may be involved. Charasse et al9 reported a case of B-cell IVL in a 71-year-old man who presented with proteinuria and was found to have renal glomerular involvement. Intravascular lymphomatosis is typically associated with a fulminant course and is inexorably fatal in untreated patients.2 Most diagnoses of IVL are made at autopsy. The delay in diagnosis is due to the peculiar location of lymphoma cells inside small vessels without involvement of lymphoid organs and associated clinical manifestations. The majority of reported IVL cases tend to disseminate rapidly and carry a poor prognosis despite chemotherapy; however, early recognition of IVL and aggressive treatment with multiagent chemotherapy may lead to prolonged remission.6 

Intravascular lymphomatosis is usually diagnosed histologically; however, more sensitive assays, including Southern blot and polymerase chain reaction techniques, may aid in diagnosis of IVL.5 Detection of an immunoglobulin heavy-chain gene rearrangement by polymerase chain reaction may identify a small clonal B-cell population in histologically negative tissue (eg, bone marrow) in IVL.5 Although immunophenotypically most cases are of B-cell lineage (Figure, C and D), rare cases of T-cell IVL have been identified, including a case of IVL of anaplastic large cell lymphoma of T-cell lineage.3,4 

Intravascular lymphomatosis coexisting with RCC appears to be unique. To the best of our knowledge, it has not been described previously. Renal cell carcinoma is the most common malignant neoplasm in the kidney, accounting for approximately 2% of all cancers. The conventional RCC is the clear cell type, comprising approximately 60% of all renal tumors. Malignant lymphoma appears only rarely as a primary renal neoplasm. More often, renal involvement is secondary to disseminated lymphoma. Renal lymphoma usually presents as a solitary or localized mass. Intravascular lymphomatosis involving kidney has been reported in several studies.2,8 Cheng et al8 reported a case of IVL presenting with encephalomyelitis and reactive hemophagocytic syndrome diagnosed by renal biopsy. The renal biopsy showed IVL with tumor cells positive for CD45 and CD20.

Lymphoma of the breast is uncommon, accounting for less than 1% of all malignant mammary neoplasms. In our case, the lymphoma involved the skin and subcutaneous tissue only. The systemic IVL in our case may be secondary to dissemination of the subcutaneous lesion or may be the primary lymphoma with the subcutaneous lesion acting as a “metastasis.”

A collision tumor contains 2 coexistent but independent primary neoplasms without a substantial histologic admixture at the interface.10 Certain collision tumors occur relatively more frequently, such as hepatocellular carcinoma and cholangiocarcinoma, gastric adenocarcinoma and lymphoma, and malignant melanoma and adenocarcinoma in the lung. Collision tumors involving the kidney are extremely rare.10 

In summary, we report an unusual case of IVL coexisting with RCC. To our knowledge, this is the first report of these unusual collision tumors in the English literature.

The authors thank Norman Katz and Joseph Samet for their excellent photographic assistance.