Imaging Analysis

A hypermetabolic lung and peritoneal masses

A 73-year-old woman presented with complaints of ongoing weight loss and intermittent abdominal discomfort. CT of the chest, abdomen and pelvis revealed a 4.3 cm × 3.8 cm spiculated left upper lobe mass and subcentimeter bilateral nonspecific pulmonary nodules. There was no evidence of mediastinal or hilar adenopathy. Imaging also revealed a 4.8 cm × 2.2 cm density in anterior abdominal wall involving the musculature, large amount of ascites, multiple omental masses. There was no evidence of bowel obstruction, but there was a 4.6 cm × 4.2 cm mesenteric mass contiguous with the walls of multiple small bowel loops, with infiltration of mesenteric fat. An FDG-PET/CT confirmed the left upper lobe spiculated mass with an standardized uptake value of 7, and several nonhypermetabolic subcentimeter bilateral lung nodules were also noted. The omental and peritoneal masses had mild-to-moderate metabolic activity with standardized uptake value between 1.7 and 3, and the mesenteric mass had standardized uptake value of 2.5. The anterior abdominal wall mass had standardized uptake value of 1.1.

The patient underwent left upper lobe resection revealing a 4.6 cm mucinous, moderately differentiated adenocarcinoma, invading overlying pleura. All lymph nodes were negative but lymphatic invasion was present. The immunohistochemistry was positive for CK7 and TTF-1 and negative for CD20, CDX2 and CA125.

She recovered without complications and underwent laparoscopy and biopsy of peritoneal mass, which was consistent with metastatic adenocarcinoma. On pathologic evaluation, this biopsy differed morphologically from the lung specimen, and was “less columnar” than the original. Immunohistochemistry was strongly positive for CK7, calretinin, D2–40, CK5/6, focally positive for WT1, negative for TTF-1, CK20, ER/PR breast 2 and CA125. This pattern was most consistent with malignant mesothelioma.

Repeat FDG-PET/CT three months later revealed numerous bilateral subpleural nonhypermetabolic nodules. The previously seen dominant mesenteric mass had increased in size by almost 3 cm in length although standardized uptake value was essentially unchanged, from 2.5 to 2.7. There was progression of nodular thickening of the greater omentum, with standardized uptake value of 2.9, increased peritoneal implants and intra-abdominal and pelvic ascites. Also, several new mildly hypermetabolic lesions were noted in the sternum, thoracic vertebrae and iliac bones.

The patient began palliative chemotherapy with cisplatinum and pemetrexed (Alimta, Eli Lilly), and tolerated the first two cycles without difficulty.

Figure 1: Initial PET/CT examination demonstrates hypermetabolic activity  associated with primary lung carcinoma
Figure 1: Initial PET/CT examination demonstrates hypermetabolic activity (yellow circle) associated with primary lung carcinoma. Upper left image is axial CT scan, upper right image is corresponding PET image, lower left image is fusion image containing PET images displayed on a color scale and CT images displayed on a gray scale. Lower right image is maximum intensity project (MIP) image of whole body PET study.

Figure 2: Initial PET/CT examination demonstrates hypermetabolic activity associated with omental implant
Figure 2: Initial PET/CT examination demonstrates hypermetabolic activity (yellow circle) associated with omental implant. Display convention is the same as Figure 1.


Figure 3: Comparison of initial and follow-up PET/CT examination
Figure 3: Comparison of initial and follow-up PET/CT examination demonstrates increasing amount of ascites. Display convention is the same as Figures 1 and 2.

Figure 4: Follow up PET/CT examination demonstrates hypermetabolic activity associated with a new mixed/sclerotic lesion in the sternum
Figure 4: Follow up PET/CT examination demonstrates hypermetabolic activity associated with a new mixed/sclerotic lesion in the sternum. Display convention is the same as Figures 1, 2 and 3.

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.

DISCUSSION

Primary peritoneal mesothelioma shares the biologic and clinical characteristics of pleural mesothelioma but is much less common, with an incidence of about one in one million. Both are associated with a history of asbestos exposure and tend to spread locally. They are often aggressive, although some patients who undergo multimodality therapy for localized disease do have prolonged survival. The median survival of patients with untreated malignant mesothelioma is four to 13 months, or six to 18 months in treated patients, with the majority dying from local chest extension and respiratory failure.

Tumor extension below the diaphragm or primary peritoneal mesothelioma may result in death from small bowel obstruction. For patients with advanced (unresectable or recurrent) peritoneal disease, palliative systemic chemotherapy is identical to that for pleural-based disease. Three randomized trials have concluded that chemotherapy with a platinum-based doublet prolongs survival compared to single-agent treatment or best supportive care.

The role of FDG-PET/CT for staging and follow-up of mesothelioma is evolving. FDG-PET/CT appears to be quite sensitive for detecting extrathoracic mesothelioma, but its sensitivity for determination of resectability and local thoracic staging may be more limited.

One study evaluated the utility of FDG-PET in the preoperative evaluation and staging of patients who were potential candidates for aggressive combined modality therapy. In 18 patients with biopsy proven malignant mesothelioma, the FDG-PET results were compared with results from staging workup including CT scan, mediastinoscopy, thoracoscopy and pathologic evaluation of biopsy specimens. All mesotheliomas were FDG-PET avid with a mean standardized uptake value of 7.6 (range 3.33-14.85; n=9). The FDG-PET evaluation did reveal occult extrathoracic metastases in two patients, which excluded them from surgery. There were no false negative FDG-PET images, but two false positives: one in the contralateral chest whose biopsy was negative and another after partial colectomy.

In another series, 28 patients with suspected malignant pleural mesothelioma were evaluated by FDG-PET imaging. Surgical biopsy confirmed the presence of malignant disease in 24 of 28 patients and demonstrated benign processes in the remaining four. The uptake of FDG was significantly higher in malignant than in benign lesions. Using a standardized-uptake value cutoff of 2.0 had a sensitivity of 91% and a specificity of 100% for malignant disease.

Another retrospective series of 60 patients with biopsy-proven malignant pleural mesothelioma were identified who had undergone FDG-PET imaging preoperatively. The clinical stage based on FDG-PET was compared with the surgical and pathologic results. The FDG-PET was positive in 59 of 60 patients, and the one false negative had only small volume pleural disease. However, the sensitivity of FDG-PET in detecting T4 (unresectable) disease was only 19%. The sensitivity for lymph node involvement was 11%.

The use of FDG-PET/CT in monitoring response to treatment has not been well studied. The small number of patients and inherent difficulty evaluating response to treatment in this disease has made phase-3 trials difficult to conduct. Both the objective response rate (measured as a decrease of >30% thickness of pleural rind perpendicular to rib on CT scan) and progression-free survival have been used as surrogates for efficacy in all the phase-3 studies to date. A decrease in hypermetabolism on FDG-PET may prove a better method to follow response to treatment but this has not yet been validated.

FDG-PET/CT is a useful tool for evaluating patients in whom one has a high index of suspicion for mesothelioma, especially those with distant metastatic disease. It is likely to be useful in following response to systemic treatment as well. It is less useful for staging and determination of resectability because the relatively low metabolic activity and characteristic pattern of spread of makes it difficult to differentiate malignant from benign processes.

For more information:

  • Schneider DB, et al. PET Positron emission tomography with f18-fluorodeoxyglucose in the staging and preoperative evaluation of malignant pleural mesothelioma. J Thorac Cardiovasc Surg. 2000;120:128-133.
  • Benard F, et al. Metabolic imaging of malignant pleural mesothelioma with fluorodeoxyglucose positron emission tomography. Chest. 1998;114:713-722.
  • Flores RM, Akhurst T, Gonen M, et al. Positron emission tomography defines metastatic disease but not locoregional disease in patients with malignant pleural mesothelioma. J Thorac Cardiovasc Surg. 2003;126:11- 16.

A 73-year-old woman presented with complaints of ongoing weight loss and intermittent abdominal discomfort. CT of the chest, abdomen and pelvis revealed a 4.3 cm × 3.8 cm spiculated left upper lobe mass and subcentimeter bilateral nonspecific pulmonary nodules. There was no evidence of mediastinal or hilar adenopathy. Imaging also revealed a 4.8 cm × 2.2 cm density in anterior abdominal wall involving the musculature, large amount of ascites, multiple omental masses. There was no evidence of bowel obstruction, but there was a 4.6 cm × 4.2 cm mesenteric mass contiguous with the walls of multiple small bowel loops, with infiltration of mesenteric fat. An FDG-PET/CT confirmed the left upper lobe spiculated mass with an standardized uptake value of 7, and several nonhypermetabolic subcentimeter bilateral lung nodules were also noted. The omental and peritoneal masses had mild-to-moderate metabolic activity with standardized uptake value between 1.7 and 3, and the mesenteric mass had standardized uptake value of 2.5. The anterior abdominal wall mass had standardized uptake value of 1.1.

The patient underwent left upper lobe resection revealing a 4.6 cm mucinous, moderately differentiated adenocarcinoma, invading overlying pleura. All lymph nodes were negative but lymphatic invasion was present. The immunohistochemistry was positive for CK7 and TTF-1 and negative for CD20, CDX2 and CA125.

She recovered without complications and underwent laparoscopy and biopsy of peritoneal mass, which was consistent with metastatic adenocarcinoma. On pathologic evaluation, this biopsy differed morphologically from the lung specimen, and was “less columnar” than the original. Immunohistochemistry was strongly positive for CK7, calretinin, D2–40, CK5/6, focally positive for WT1, negative for TTF-1, CK20, ER/PR breast 2 and CA125. This pattern was most consistent with malignant mesothelioma.

Repeat FDG-PET/CT three months later revealed numerous bilateral subpleural nonhypermetabolic nodules. The previously seen dominant mesenteric mass had increased in size by almost 3 cm in length although standardized uptake value was essentially unchanged, from 2.5 to 2.7. There was progression of nodular thickening of the greater omentum, with standardized uptake value of 2.9, increased peritoneal implants and intra-abdominal and pelvic ascites. Also, several new mildly hypermetabolic lesions were noted in the sternum, thoracic vertebrae and iliac bones.

The patient began palliative chemotherapy with cisplatinum and pemetrexed (Alimta, Eli Lilly), and tolerated the first two cycles without difficulty.

Figure 1: Initial PET/CT examination demonstrates hypermetabolic activity  associated with primary lung carcinoma
Figure 1: Initial PET/CT examination demonstrates hypermetabolic activity (yellow circle) associated with primary lung carcinoma. Upper left image is axial CT scan, upper right image is corresponding PET image, lower left image is fusion image containing PET images displayed on a color scale and CT images displayed on a gray scale. Lower right image is maximum intensity project (MIP) image of whole body PET study.

Figure 2: Initial PET/CT examination demonstrates hypermetabolic activity associated with omental implant
Figure 2: Initial PET/CT examination demonstrates hypermetabolic activity (yellow circle) associated with omental implant. Display convention is the same as Figure 1.


Figure 3: Comparison of initial and follow-up PET/CT examination
Figure 3: Comparison of initial and follow-up PET/CT examination demonstrates increasing amount of ascites. Display convention is the same as Figures 1 and 2.

Figure 4: Follow up PET/CT examination demonstrates hypermetabolic activity associated with a new mixed/sclerotic lesion in the sternum
Figure 4: Follow up PET/CT examination demonstrates hypermetabolic activity associated with a new mixed/sclerotic lesion in the sternum. Display convention is the same as Figures 1, 2 and 3.

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.

DISCUSSION

Primary peritoneal mesothelioma shares the biologic and clinical characteristics of pleural mesothelioma but is much less common, with an incidence of about one in one million. Both are associated with a history of asbestos exposure and tend to spread locally. They are often aggressive, although some patients who undergo multimodality therapy for localized disease do have prolonged survival. The median survival of patients with untreated malignant mesothelioma is four to 13 months, or six to 18 months in treated patients, with the majority dying from local chest extension and respiratory failure.

Tumor extension below the diaphragm or primary peritoneal mesothelioma may result in death from small bowel obstruction. For patients with advanced (unresectable or recurrent) peritoneal disease, palliative systemic chemotherapy is identical to that for pleural-based disease. Three randomized trials have concluded that chemotherapy with a platinum-based doublet prolongs survival compared to single-agent treatment or best supportive care.

The role of FDG-PET/CT for staging and follow-up of mesothelioma is evolving. FDG-PET/CT appears to be quite sensitive for detecting extrathoracic mesothelioma, but its sensitivity for determination of resectability and local thoracic staging may be more limited.

One study evaluated the utility of FDG-PET in the preoperative evaluation and staging of patients who were potential candidates for aggressive combined modality therapy. In 18 patients with biopsy proven malignant mesothelioma, the FDG-PET results were compared with results from staging workup including CT scan, mediastinoscopy, thoracoscopy and pathologic evaluation of biopsy specimens. All mesotheliomas were FDG-PET avid with a mean standardized uptake value of 7.6 (range 3.33-14.85; n=9). The FDG-PET evaluation did reveal occult extrathoracic metastases in two patients, which excluded them from surgery. There were no false negative FDG-PET images, but two false positives: one in the contralateral chest whose biopsy was negative and another after partial colectomy.

In another series, 28 patients with suspected malignant pleural mesothelioma were evaluated by FDG-PET imaging. Surgical biopsy confirmed the presence of malignant disease in 24 of 28 patients and demonstrated benign processes in the remaining four. The uptake of FDG was significantly higher in malignant than in benign lesions. Using a standardized-uptake value cutoff of 2.0 had a sensitivity of 91% and a specificity of 100% for malignant disease.

Another retrospective series of 60 patients with biopsy-proven malignant pleural mesothelioma were identified who had undergone FDG-PET imaging preoperatively. The clinical stage based on FDG-PET was compared with the surgical and pathologic results. The FDG-PET was positive in 59 of 60 patients, and the one false negative had only small volume pleural disease. However, the sensitivity of FDG-PET in detecting T4 (unresectable) disease was only 19%. The sensitivity for lymph node involvement was 11%.

The use of FDG-PET/CT in monitoring response to treatment has not been well studied. The small number of patients and inherent difficulty evaluating response to treatment in this disease has made phase-3 trials difficult to conduct. Both the objective response rate (measured as a decrease of >30% thickness of pleural rind perpendicular to rib on CT scan) and progression-free survival have been used as surrogates for efficacy in all the phase-3 studies to date. A decrease in hypermetabolism on FDG-PET may prove a better method to follow response to treatment but this has not yet been validated.

FDG-PET/CT is a useful tool for evaluating patients in whom one has a high index of suspicion for mesothelioma, especially those with distant metastatic disease. It is likely to be useful in following response to systemic treatment as well. It is less useful for staging and determination of resectability because the relatively low metabolic activity and characteristic pattern of spread of makes it difficult to differentiate malignant from benign processes.

For more information:

  • Schneider DB, et al. PET Positron emission tomography with f18-fluorodeoxyglucose in the staging and preoperative evaluation of malignant pleural mesothelioma. J Thorac Cardiovasc Surg. 2000;120:128-133.
  • Benard F, et al. Metabolic imaging of malignant pleural mesothelioma with fluorodeoxyglucose positron emission tomography. Chest. 1998;114:713-722.
  • Flores RM, Akhurst T, Gonen M, et al. Positron emission tomography defines metastatic disease but not locoregional disease in patients with malignant pleural mesothelioma. J Thorac Cardiovasc Surg. 2003;126:11- 16.