The patient is a 40-year-old man diagnosed with HIV infection on routine
screening in 2005. He was not started on antiretroviral therapy at that time.
In January 2008, he developed fatigue, fevers, chills, night sweats, decreased
appetite and a 5-lb weight loss. No acute infectious cause was found, and he
was started on HAART therapy at that time. His fever did not abate with
treatment, and he grew increasingly fatigued, eventually requiring
hospitalization. He was found to have severe normocytic anemia with hemoglobin
6.6 gm/dL, white blood cell 4.2 with normal differential and platelets of
740,000 without evidence of hemolysis.
His chest X-ray revealed diffusely increased lung markings with
peribronchial thickening, and no focal infiltrate. A bone marrow biopsy was
hypercellular to 95%, with more than 50% marked fibrosis and associated
histiocytes, eosinophils and focal atypical cells with prominent nucleoli,
typical of Reed-Sternberg cells. The immunostains were consistent with a
diagnosis of Hodgkins disease. An initial CT scan of the chest, abdomen
and pelvis revealed multiple bilateral tiny nodularities scattered along
bronchovascular bundles and periphery, in addition to widespread lymph nodes
measuring <1 cm and numerous small-lowdensity liver lesions as large
as 3 cm in the right lobe. Biopsy of a liver lesion was nondiagnostic.
Subsequent PET/CT revealed bilateral multiple tiny nodularities scattered along
periphery and bronchovascular bundles, more prominent on the right with a
standardized uptake value up to 3.0, in addition to axillary, mediastinal,
hilar lymph nodes with minimal hyperactivity, a mildly enlarged spleen without
focal lesions, mild hepatomegaly without discrete lesions and subcentimeter
retroperitoneal and iliac chain lymph nodes with standardized uptake value to
Figure 1: CT scan of the chest demonstrates multiple bilateral tiny nodularities scattered along the periphery and the bronchovascular bundles (arrow).
Figure 2: Staging PET/CT examination demonstrates hypermetabolic activity (arrow) associated with these lung nodules. Upper left image is axial CT scan, upper right image is corresponding PET image, lower left image is fusion of PET and CT images displayed on color vs. gray scale, and lower right image is maximal intensity projection PET image.
On the first hospitalization, HAART was continued and prophylactic
antibiotics were started. The patient was hospitalized a second time prior to
treatment for persistent fever and absolute neutropenia. Broad spectrum
antibiotics were initiated, although all cultures remained negative, and
prophylactic medications were stopped. A repeat bone marrow biopsy was done
that again revealed classical Hodgkins lymphoma trilineage maturing
hematopoeisis with myeloid hypoplasia, left shifted myeloid maturation with
marked decreased to absent mature forms. The patient was treated with
granulocyte colony-stimulating factor and counts normalized.
He began treatment with ABVD in May 2008 and developed fever chills and
rigors during treatment IA, but this was thought to be related to cytokine
release from the lymphoma and bleomycin was held only for one cycle, then
reinitiated without difficulty. Restaging PET/CT after cycle IIIB was
consistent with interval resolution of previously identified branching nodular
opacicites in both lungs, and resolution of mild hepatospenomegaly, and
interval decrease in size of lymphadenopathy, without residual hypermetabolic
Figure 3: Staging PET/CT examination demonstrates low-grade hypermetabolic activity associated with left axillary lymph node (arrow).
Figure 4: Comparison of staging and follow-up PET/CT examination demonstrates interval decrease in size of the left axillary lymph node (arrows). This lymph node is no longer hypermetabolic.
Figure 5: Comparison of staging and follow up PET/CT examination demonstrates interval resolution of hypermetabolic lung nodularities (arrows).
Source: M Ghesani
Munir Ghesani, MD, is Associate Clinical Professor of Radiology at
Columbia University College of Physicians and Surgeons and Attending
Radiologist at St. Lukes-Roosevelt Hospital Center.
Carrie Wasserman, MD, is a second year Hematology/Oncology Fellow at St.
Lukes-Roosevelt Hospital Center.
Anupama Goel, MD, is an Attending Physician in the Division of Hematology
& Oncology at St. Lukes-Roosevelt Hospital Center.
Several epidemiologic studies have demonstrated a three- to 18-fold
increased risk of Hodgkins disease in patients with AIDS, although
Hodgkins disease is not considered an AIDS-defining cancer.
It was one malignancy (other than AIDS-defining cancers) that was
associated with advancing immunosuppression in an analysis of over 302,000
adults in a linked population-based AIDS and cancer registry data from the
United States in 2001.
The pathologic spectrum of Hodgkins disease differs for HIV-infected
patients compared to those without HIV in the United States. Hodgkins
disease in patients with HIV is most often the mixed cellularity histologic
subtype compared to the non-HIV population in which the nodular sclerosis type
predominates. The involved tissue in patients with HIV and Hodgkins
disease contain characteristic fibrohistiocytic stromal cells as well.
These patients are more likely to present with advanced disease, and more
often present with B symptoms, bone marrow involvement and
It has been demonstrated that the response rate of patients receiving
standard chemotherapy with antiretroviral treatment was similar to response
rates of non-HIV patients. The rate of opportunistic infections is
significantly lower in patients with HIV treated with antiretrovirals compared
to those treated without HAART. The addition of granulocyte colony-stimulating
factor does not improve outcomes.
The incidence of HIV Hodgkins disease does not appear to have
decreased in the HAART compared to pre-HAART era and may have actually
increased. Patients may now be presenting with less advanced disease and
therefore their outcomes may be better. Studies have clearly shown that
antiretroviral medication in addition to intensive chemotherapy improves
The timing of initiation of HAART and chemotherapy can be difficult because
if started simultaneously, it can be impossible to know which treatment is
working. Oftentimes though, both treatments must be started at nearly the same
time. Since these mildly hypermetabolic subcentimeter lung nodules were present
after almost three months of antiretroviral therapy, and then resolved with
chemotherapy suggests that they were more likely malignant than infectious, but
one cannot be absolutely certain.
For more information:
- Errante D, et al. Combined antineoplastic and antiretroviral therapy for
patients with Hodgkins disease and human immunodeficiency virus
infection. A prospective study of 17 patients. The Italian Cooperative Group on
AIDS and Tumors (GICAT). Cancer. 1994;73:437-44.
- Errante D, et al. Hodgkins disease in 35 patients with HIV infection:
an experience with epirubicin, bleomycin, vinblastine and prednisone
chemotherapy in combination with antiretroviral therapy and primary use of
G-CSF. Oncol. 1999;10:189-95.
- Frisch M, et al. Association of cancer with AIDS-related immunosuppression
in adults. JAMA. 2001;285:1736-45.