Imaging Analysis

Resolution of pulmonary nodules in Hodgkin’s disease and HIV

Initiating HAART and chemotherapy may be a challenge in these patients.

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 Hodgkin’s 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-low–density 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 3.6.

Figure 1: CT scan of the chest
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
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 Hodgkin’s 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 activity.

Figure 3: Staging PET/CT examination
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
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
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. Luke’s-Roosevelt Hospital Center.

Carrie Wasserman, MD, is a second year Hematology/Oncology Fellow at St. Luke’s-Roosevelt Hospital Center.

Anupama Goel, MD, is an Attending Physician in the Division of Hematology & Oncology at St. Luke’s-Roosevelt Hospital Center.

CASE DISCUSSION

Several epidemiologic studies have demonstrated a three- to 18-fold increased risk of Hodgkin’s disease in patients with AIDS, although Hodgkin’s 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 Hodgkin’s disease differs for HIV-infected patients compared to those without HIV in the United States. Hodgkin’s 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 Hodgkin’s 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 extranodal disease.

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 Hodgkin’s 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 outcomes.

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 Hodgkin’s 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. Hodgkin’s 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.

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 Hodgkin’s 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-low–density 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 3.6.

Figure 1: CT scan of the chest
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
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 Hodgkin’s 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 activity.

Figure 3: Staging PET/CT examination
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
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
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. Luke’s-Roosevelt Hospital Center.

Carrie Wasserman, MD, is a second year Hematology/Oncology Fellow at St. Luke’s-Roosevelt Hospital Center.

Anupama Goel, MD, is an Attending Physician in the Division of Hematology & Oncology at St. Luke’s-Roosevelt Hospital Center.

CASE DISCUSSION

Several epidemiologic studies have demonstrated a three- to 18-fold increased risk of Hodgkin’s disease in patients with AIDS, although Hodgkin’s 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 Hodgkin’s disease differs for HIV-infected patients compared to those without HIV in the United States. Hodgkin’s 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 Hodgkin’s 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 extranodal disease.

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 Hodgkin’s 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 outcomes.

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 Hodgkin’s 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. Hodgkin’s 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.