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1634 Part XI: Malignant Lymphoid Diseases Chapter 98: Diffuse Large B-Cell Lymphoma and Related Diseases 1635

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Therapy number of reactive lymphocytes in the background. Grade 1 lesions
Several regimens have been evaluated in PMBCL. A retrospective study contain a polymorphous lymphoid infiltrate without cytologic atypia.
compared the outcomes of 426 patients who had fibrotic tumor reac- Large transformed lymphoid cells are absent or rare and EBV-positivity
tions (sclerosis) and previously untreated disease using CHOP-like regi- is detectable in only a few cells. Grade 2 lesions contain occasional large
mens, third-generation (MACOP-B, VACOP-B [etoposide, doxorubicin, lymphoid cells or immunoblasts in a polymorphous background. In situ
cyclophosphamide, vincristine, prednisone, and bleomycin], ProMACE hybridization for EBV readily identifies EBV-positive cells, which are
CytaBOM) regimens, or high-dose chemotherapy with autologous hemato- present at 5 to 20 per high-power field. Grade 3 lesions continue to show
poietic stem cell transplantation. With chemotherapy, the CR rates were an inflammatory background, but contain frequent large atypical B cells
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49, 51, and 53 percent with first-generation, third-generation, and high- that are CD20-positive. By in situ hybridization, EBV-positive cells are
dose chemotherapy treatments, respectively. All patients who achieved CR numerous (>50/high-power field).
or PR had radiation therapy to the mediastinum. The final CR rates were
61 percent for CHOP-like regimens, 79 percent for MACOP-B and other Therapy and Prognosis
regimens, and 75 percent for high-dose chemotherapy/autologous hemato- The clinical prognosis is variable in lymphomatoid granulomatosis
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poietic stem cell transplantation. Projected 10-year PFS rates were 35, 67, with a median survival of 2 years. Poor prognostic features include
and 78 percent, respectively, and projected 10-year OS rates were 44, 71, neurologic involvement and higher pathologic grade. The disease is
and 77 percent, respectively. uncommon and the optimal treatment regimen is unclear. In a pro-
In another retrospective study of 138 patients with PMBCL the spective study, patients with grades I and II disease were treated with
effectiveness of two chemotherapy regimens (CHOP vs. MACOP-B/ interferon-α, whereas those with grade III lesions received dose-
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VACOP-B) and the role of mediastinal IFRT as consolidation were eval- adjusted R-EPOCH chemotherapy. Among 27 patients with grade I or
uated. CR occurred in 51 percent of the CHOP group and 80 percent II disease treated with interferon-α, 56 percent were in continuous CR
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in MACOP-B/VACOP-B. EFS was 40 percent with CHOP and 76 per- for a median of 52 months. Among grade III patients treated with dose-
cent in the MACOP-B/VACOP-B group. The addition of IFRT improved adjusted R-EPOCH, 40 percent achieved CR, with OS and PFS rates of
the outcome, regardless of the type of chemotherapy used. The incor- 69 and 82 percent, respectively, after a median follow up of 46 months.
poration of rituximab in the dose-adjusted EPOCH regimen, without
radiotherapy consolidation, resulted in 97 percent OS and 93 percent INTRAVASCULAR LARGE B-CELL LYMPHOMA
EFS in a nonrandomized, phase II clinical trial. Based on this study,
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which included 5-year followup data, many authorities believe that the Definition
dose-adjusted R-EPOCH regimen should be the preferred firstline regi- Intravascular large B-cell lymphoma is a rare type of extranodal large
men for this entity, without routine incorporation of radiotherapy. B-cell lymphoma characterized by selective growth of lymphoma cells
within the lumina of vessels, sparing the large arteries and veins. 2
LYMPHOMATOID GRANULOMATOSIS Epidemiology
Definition This tumor usually occurs in adults in the sixth and seventh decade. It
Lymphomatoid granulomatosis is a rare lymphoproliferative disorder occurs equally in men and women.
characterized by angiocentric and angiodestructive Epstein-Barr virus
(EBV)–driven B-cell proliferation associated with extensive reactive Clinical Features
T-cell infiltration. 2 The clinical manifestations of this lymphoma are extremely variable,
with most symptoms related to the organs affected. Two major patterns
Epidemiology of clinical presentation have been recognized: the first is in European
Approximately two-thirds of cases occur in males. The median age of countries with brain and skin involvement and the second in the Asian
presentation is in the fifth decade of life, although pediatric cases occur. countries where patients typically present with multiorgan failure, hepa-
tosplenomegaly, pancytopenia and hemophagocytic syndrome. 125–129 B
Clinical Features symptoms (fever, drenching sweats, and weight loss) are common in
The lung is the most common site of involvement (90 percent), fol- both types. An isolated cutaneous variant almost unique to Western
lowed by the skin (25 to 50 percent), kidney (30 to 40 percent), liver countries has been identified in females and is associated with a better
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(29 percent), and CNS (26 percent). The spleen and the lymph nodes prognosis. In this variant, skin lesions range from single to striking
are uncommonly involved. Nearly all patients are symptomatic at pre- clusters of nodules and tumors which may appear as violaceous plaques,
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sentation with cough, dyspnea, chest pain, fever, weight loss, and joint erythematous nodules, or ulcerating tumors, which are often painful.
pain. Abdominal pain and diarrhea occur as a result of gastrointestinal These lesions commonly appear on the arms and legs, abdomen and
involvement and various neurologic signs, including diplopia, ataxia, breasts, but may occur anywhere.
and mental status changes may occur as a result of CNS involvement.
Skin manifestations are clinically diverse, and include ulcerations, Laboratory Features
plaques, and maculopapules, although subcutaneous nodules are most There are no laboratory findings specific for intravascular B cell lym-
common. phoma. Increased LDH and β -microglobulin levels are observed in
2
most patients. An elevated erythrocyte sedimentation rate and abnor-
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Laboratory Features malities in hepatic, renal, and thyroid function are also common.
Imaging Studies Pulmonary involvement typically involves bilateral, Tumor cells express B-cell–associated antigens and occasionally express
lower lobe nodules, which frequently cavitate. Nodules may also be CD5.
found in the brain and kidney and other locations.
Histopathology The grading of lymphomatoid granulomato- Therapy
sis depends upon the proportion of EBV-positive B cells identified by Anthracycline-based chemotherapy is the standard of care for this
in situ hybridization with an EBV-encoded RNA probe relative to the type of lymphoma and retrospective studies suggest that the addition

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