BONE IMAGING OF MALIGNANT DISEASES

  1. Patterns of Metastatic Disease
    1. Solitary lesion* - Metastatic disease appears as a single lesion only 6-8% of the time (usually appears multiple). Shirazi et al. noted that of the first 100 solitary lesions on a bone scan, 54% were due to metastatic disease. In a study of 1,129 patients (Corcoran, et al), 15% of patients had single lesions; of this, 64% were determined to be metastatic on follow-up examination. The most common areas in which single lesions were metastatic were noted in the pelvis and spine. Local tenderness and metastatic disease have a high degree of correlation.
      1. Rule of thumb - lesions in the spine are probably metastatic.
      2. When two lesions are seen, the etiology usually becomes clearer. Ex: Two lesions adjacent to ribs are probably due to trauma. However, two on the same rib (or scattered) is probably metastatic disease.
      3. Lucent lesions cannot be seen and may be due to myeloma or rapidly expanding anaplastic disease. The key to having radionuclide uptake is that the lesion must be blastic in nature. Most are.
      4. One might conclude that a single lesion has a >50% probability of being metastatic if the patient's history does not indicate trauma or infection.
    2. Regional Disease* - Most common is breast ca where a local invasion of tumor invades the internal mammary node chain that metastasizes to the sternum and/or ribs. Lesions favor the side of the primary cancer. Prostatic carcinoma dominates the lower quadrant of the pelvic area and then moves to the extremity.
    3. Wide Dissemination* is a common pattern with random distribution throughout the axial skeleton. Distal long bones are rarely involved but cannot be excluded.
    4. Local Invasion - Occasionally, the observer notes invasion to adjacent bone from a soft tissue tumor. Examples are mandible by a tumor in/on the tongue or floor of the mouth or a single lesion on the ANT aspect of the spine at the same level as where the esophageal tumor is located.
    5. Photopenic Disease* - Usually results in the end stage destruction of bone metastases. Mostly seen in flat bones. However, as the tumor moves out of the area, a hyperemic rim may be noted. The example given is Chordoma. However, it should be noted that this type of bone disease is not cancerous and is considered benign. A brief overview of what other types of diseases in the bone might cause photopenic, see discussion.
    6. Dominant Metaphyseal Involvement - is usually seen in children (ex. osteosarcoma).
    7. Dominant Peripheral Skeleton Mets - involves the diaphyseal portions of long bones as compared to the central skeleton. This usually indicates a primary lesion of marrow or lymph node, such as leukemia or lymphoma.
    8. Bone-producing Metastasis* - Seen rarely, lesion of intense uptake extends beyond the bone margin into the soft tissue. This implies that bone producing elements are within a metastatic tumor. Can be osteosarcoma, however, (non-bone) cervix, endometrium, and ovary cancers are common. Example - https://www.karger.com/Article/Fulltext/339198
    9. Soft Tissue Manifestation of Malignant Disease* - Tumors can affect fluid dynamics in their region, therefore resulting in radionuclide retention in the affected area. For example, pelvic tumor may retain traces of increased levels of edema; post-mastectomy may have lymphedema of the arm, which implies the presence of obstructive tumor along the lymph chain.
      1. Example of activity found in the peritoneal cavity. This may be due to the primary tumor of the liver that caused a pleural effusion of the thorax.
    10. Bone-producing Metastases* - Unusual pattern that is rarely seen. Bone lesion is of intense uptake that extends beyond the bone into the soft tissue. The tumor usually occurs from non-skeletal bone metastases and is most common in the cervix, endometrium, and ovarian cancers.
  2. Lesions and types of Cancer
    1. General comment: A major issue that is brought up is whether or not a bone scan is necessary given the specific type of cancer. Pending the type of disease present (cancer), a bone scan may be recommended to determine metastatic involvement. Or, in the situation where metastatic disease is identified, staging of the disease becomes important to determine the type of therapy to administer.
    2. Lung Cancer
      1. Preoperative bone scan imaging is recommended even though it has a low yield in identifying disease. This is due to a high operative mortality. Symptomatic patients are 32% positive at stages I and II, and 41% positive at stage III. A positive bone scan indicates a 40-46% death rate within six months. However, in the revised text, the author argues that bone imaging should not be done on the preoperative patient since it has a relatively low yield of finding disease.
        1. Hematogenous dissemination occurs via arterial circulation (where the breast and prostate are venous). Therefore, mets can go peripherally anywhere, but it is rare to find it in the hands and feet.
        2. Most common patterns: Direct invasion to the chest wall, particularly upper rib by Pancoast tumor; it may just go to chest wall and not disseminate in to pleural involvement.
    3. Breast Cancer
      1. Bone imaging will show metastatic involvement 4 to 6 months before it appears in a skeletal survey (x-ray). However, the use of bone scintigraphy remains controversial, which is due to its low true positive rate.
      2. Stage I and II are 20% to 38%, respectively, positive for mets. However, reported in the literature is as little as 7 to 8 percent in Stages I and II.
      3. Therefore, a nuke study in the early stages or as a preoperative scan varies to need. One can argue the importance of establishing a baseline, noting a negative bone scan (which becomes positive over time), that results in a change in the patient's therapy.
      4. Gerber et al. reported a 21% of patients converted to a positive study in within two years post-surgery, while Robbins et al. reported a 9.5 % conversion rate in ten years with patients with negative nodes.
      5. The universal agreement is that all patients with advanced disease (stage II) need to have a bone scan.
      6. Common patterns:
        1. The most common pattern is local invasion (bone) by regional nodes. Most occur from the internal mammary chain with a signal lesion on the sternum of the involved side. Usually doesn't go widespread.
        2. The second most common pattern is a regional pattern in 2 to 5 contiguous posterior ribs on the proximal side and may involve the spine (usually between the 3 and 9th ribs). This is usually seen within 18 months post radical mastectomy.
  3. Prostate Cancer
    1. Radionuclide bone imaging is extensively used for early detection of metastatic disease as well as staging.
    2. Stage I = 5%, Stage II = 10%, Stage III = 20% have positive bone scans. If serum acid phosphatase levels are up, the value jumps to 30%.
    3. Serial bone scanning is helpful in evaluating and treating the disease. Regression of mets indicates that therapy is working and is considered a good prognosis. If the follow up scans remain negative for 6 to 12 months, survival rates become 60 and 88%, respectively.
    4. Increased levels of prostatic acid phosphatase (PSA) indicate the possible spreading of prostate cancer, which correlates to positive bone scintigraphy. Miller, et al. showed that all patients with a positive bone scan had PSA levels equal to or greater than 20 ng/ml.
    5. Common patterns:
      1. Regional mets with a dominant quadrant in the pelvis region are common. Ranges from a small cluster of lesions to the entire hemipelvis and/or extending down the femur, which mimics Paget's disease. Urinary tract obstruction or extremity edema may not initially be present and/or may occur over the course of the disease.
      2. Widely disseminated mets are remarkable in prostate cancer. It goes everywhere and is sometimes referred to as a Superscan.
  4. Genitourinary Tract Cancer - It Isn't helpful as a diagnostic tool. Both renal and bladder cancers have a low detection rate in all stages, with only a 5% detection rate being reported. However, at end-stage, bone involvement it is usually seen in the central skeleton.
  5. Female Genital Tract Carcinoma
    1. Similar to #4, however, it may be helpful in patients that have recurrent disease.
    2. Two patterns were noted:
      1. Blood-borne with randomly distributed multi-focal lesions leads to a poor prognosis.
      2. Concentrated in the lumbar spine, particularly on the left side, due to paravertebral lymph node chain involvement. Responds well to radiation. Seen mostly in cervical cancer. It also attacks the kidneys more so than bone, and if a bone scan is done, renal involvement may be noted.
      3. Exophytic uptake sometimes occurs in patients that have gynecologic types of cancer. Sometimes this pattern is seen with a clinically silent tumor.
  6. GI Track Carcinoma
    1. An oral lesion will appear in the mandibular or maxillary bone. Esophageal lesions can spread to the adjacent spine but usually to the upper two-thirds of the throat. Stomach cancer goes to the liver and bone. Pancreas cancer invades the lower ribs and adjacent spine. A bone scan for colon cancer is not recommended.
  7. Tumors of Marrow and Lymph Node Origin
    1. Lymphoma and bone involvement are rare. However, if skeletal mets are expected, this is the procedure of choice even though it has a high false-negative rate. Usually, it is seen in the long bone and more routinely in the diaphysis, in which activity is usually equal to or greater than the activity in the central skeletal system.
    2. Leukemia is of little help; however, if noted, it involves the peripheral skeleton as much or more than the central.
    3. Thyroid Cancer is generally ineffective, however, 131I is the whole body scan agent of choice.
    4. Melanoma and Multiple Myeloma both do not pick up the bone agent very well.
    5. Neuroblastoma can be visualized in bone scintigraphy, however, MIBG is more sensitive and specific to the disease. (Bone 78 sensitivity and 51% specific) (MIBG is 90% sensitive and 100% specific).
    6. In general, 68Ga-DOTATATE is the agent of choice when it comes to neuroendocrine tumors. The website discusses the use of this radiopharmaceutical in its hunt for disease. We will discuss this preferred agent in your senior year.
    7. 18F-FDG is another agent that is used to image lymphatic diseases - Lymphoma (B-Cell) and Non-Hodgkin's lymphoma
  8. Primary Bone Tumors
    1. Two major indications: malignant or benign. Nukes cannot always differentiate between malignant and benign. For a period of time, bone uptake cannot occur in patients that have received radiation therapy at a disease site.
    2. Osteosarcoma is noted in soft tissue uptake as metastatic involvement invades the body.
    3. Ewing's Sarcoma will show multiple lesions 33 to 45% of the time in the initial scan. In negative studies, it should be followed out for two years.
    4. Chondrosarcoma can be malignant or a benign tumor that is of cartilaginous origin. Although benign, it tends not to be as hot; this is not an indication of it being benign. Patients should have a bone scan to determine the course of therapy.
    5. Osteoid Osteoma is a benign bone tumor that is very hot sometimes and is referred to as having "double uptake" and is nicknamed "nidus."
    6. Ewing's sarcoma usually arises from the femur or pelvis and is the second most common tumor in children and young adults. Usually reveals intense uptake in a three phase bone scan and may be mistaken for osteomyelitis. Soft tissue uptake is less common. Ewing sarcoma usually spreads to the lung and bones.
  9. Na18F vs MDP
    1. MDP and Na18F have been compared in the evaluation of metastatic workup with the discovery that the PET procedure seems more sensitive in finding disease.
    2. This research article evaluates 40 patients with a whole body bone scan vs. an Multi-FOV SPECT procedure, PET
    3. What do you conclude?
    4. In another patient, the use of MDP and FDG is applied to a patient that has prostate cancer. The reason why uptake varies relates to MDP goes to blastic lesions, and 18F goes to lytic, this is according to Cook GJ, et al.1
    5. In another presentation of the disease, 18FDG and Na18F are compared.2

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9/22

1. Detection of Bone Metastases in Breast Cancer by 18FDG PET: Differing Metabolic Activity in Osteoblastic and Osteolytic Lesions by Cook GJ, et al

2. Novel Strategy for a Cocktail 18F-Flouride and 18F-FDG PET/CT Scan for Evaluation of Malignancy: Results of the Pilot-Phase Study by Iagaru A, et al.