Down Deep Differentiating Sentinel Nodes
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| Top: Planar lymphoscintigraphy shows lymphatic drainage from a breast tumor to the sentinel nodes; SPECT/CT shows the exact location of these nodes (i.e. within the breast and in the axilla). Bottom: Sentinel lymph node imaging in breast cancer, draining to sentinel nodes in the breast, in the internal mammary chain and in the axilla: planar lymphoscintigraphy vs. SPECT/CT in coronal and transaxial projections vs. 3D-volume rendered image. At surgery, all these nodes were confirmed to have microscopic metastases, not shown by a previous FDG-PET/CT scan. Image source: Cornelis A. Hoefnagel, MD, PhD, The Netherlands Cancer Institute, Amsterdam |
A sentinel lymph node is the first filter which tumor cells must pass, before spreading to other lymph nodes and organs. Instead of resecting all the lymph nodes to manage the lymphatic spread, only the sentinel nodes are excised and histopathological examination performed to detect metastatic cells. If the sentinel node is tumor negative, the patient is spared more extensive surgery and possible complications, such as lymphoedema.
SPECT/CT + lymphoscintigraphy
Only in cases where the sentinel nodes are found to be tumor positive, other lymph nodes will be removed—a necessary and curative operation. However, for this to be effective, it is imperative that the correct sentinel node is identified and removed. For this purpose, sentinel node lymphoscintigraphy is used, in many cases combined with SPECT/CT for correct anatomical localization, shares Cornelis A. Hoefnagel, MD, PhD, director of the department of nuclear medicine at the Netherlands Cancer Institute, Amsterdam. The role of SPECT/CT in sentinel node lymphoscintigraphy is to identify the sentinel node and localize it, so that it can be reliably removed for microscopic exam. “SPECT/CT can not determine whether the node is tumor positive or negative. This has to be confirmed by pathological exam,” says Hoefnagel. To localize the sentinel node, the SPECT tracer used is a technetium-99m-labeled microcolloid, which is injected in or around the tumor and is drained by the lymphatics, first to the sentinel nodes and later also to other nodes called second echelon nodes, Hoefnagel adds.The lymphoscintigram serves as a roadmap for the surgeon. The location of the sentinel node is marked on the skin and highlighted on the SPECT/CT fused images. The surgeon then finds the sentinel node, using a gamma probe, which detects the radioactive signal, describes Hoefnagel. “SPECT/CT not only tells the surgeon where the sentinel node is but how many sentinel nodes are there [in cases where there are more than one sentinel lymph node],” says Michael S. Sabel, MD, associate professor of surgery at the University of Michigan Health Systems, Ann Arbor, Mich. “SPECT/CT is a wonderful technique for surgeons in terms of identifying sentinel nodes particularly in the head and neck and upper trunk lesions where the drainage can be variable and very tricky to delineate on a lymphoscintigram. However, SPECT/CT doesn’t serve as a substitute for doing the sentinel node biopsy, but instead helps the surgeon find and remove the sentinel node which is then analyzed histopathologically,” he says.
Sentinel lymph node imaging with SPECT/CT is no longer restricted for accurate localization of sentinel nodes in breast cancer and melanoma. For instance, the types of cancers in which the Netherlands Cancer Institute routinely performs sentinel lymph node imaging with SPECT/CT are: breast cancer, melanoma, Merkel cell tumor, head and neck cancer, penile cancer, vulvar carcinoma, testicular carcinoma, prostatic cancer and renal cell carcinoma, according to Hoefnagel.
Why not PET/CT?
PET/CT or SPECT/CT fusion images enable visualization of the tumor or the lymph node in relation to all anatomical structures (such as bones, muscles and blood vessels), which are relevant for surgery. In addition, three-dimensional, volume-rendered (3DVR) images are helpful in orientation prior to surgery, adds Hoefnagel. PET/CT is designed to detect tumors and their metastases, including lymph node metastases. FDG, an aspecific tumor seeking agent, is the most widely used as PET/CT tracer and is useful in the detection, staging and treatment response monitoring of tumors. “It will detect malignant lymph nodes, provided that the tumor is FDG-avid [not all are] and that the lymph node has a certain size,” says Hoefnagel. For example, some mucinous tumor types, prostatic cancers, lobular breast carcinomas, neuroendocrine tumors, bronchioloalveolar cell carcinomas and carcinoids are not FDG-avid. Nevertheless, most tumor types can be demonstrated well by FDG-PET/CT. “For those tumors which are not FDG-avid, we may perform PET/CT using alternative radiopharmaceuticals, which these tumors can take up [e.g. prostatic cancers can be studied with Fluor-18 choline PET/CT, neuroendocrine tumors with Fluor-18 DOPA or Gallium-68 DOTATOC],” says Hoefnagel.There are issues related to size of lymph node as well and false negative outcomes that may arise in lymph nodes that contain micro-metastases. “Nodes less than 8 to 10 mm are usually not identifiable assuming that the volume of potential tumor in the node would be proportionally low,” shares Ania Z. Kielar, MD, from the department of diagnostic imaging at the Ottawa Hospital in Ottawa, Ontario, and Robert H. El-Maraghi, MD, from the department of oncology at the Royal Victoria Hospital in Barrie, Ontario, Canada.
In patients who had undergone surgery, the old scar is not metabolically active and will not show uptake on PET and is very helpful, notes Kielar and El-Maraghi. But showing the difference between inflammation, infection and recurrence in a recent post-operative patient can be difficult using PET/CT as macrophages can accumulate the FDG in a large amount as well. The more diffuse the area, the more likely it is inflammation, but a focus of malignancy could be missed in that area, adds Kielar and El-Maraghi.
Spatial resolution of PET/CT also is not sufficient for identifying a sentinel lymph node, shares Kielar and El-Maraghi. The two conducted a systematic literature review comparing PET/CT with sentinel lymph node biopsy for staging local lymph nodes in patients with melanoma. They concluded that sentinel lymph node biopsy was superior to PET for local lymph node staging in patients with intermediate-risk melanoma. The likelihood of PET/CT identifying distant metastases in melanoma was equally low because of the small risk for having distant metastases at diagnosis (J Am Coll Radiol 2008;5:924-931).
Challenges ahead
The limitations of PET/CT come from the fact that microscopic disease in lymph nodes may be missed and that the current tracers used are aspecific showing other nodal pathologies. The development of more specific tracers may help overcome these problems.Cost and radiation exposure are other limitations of using PET/CT and SPECT/CT, according to Brian Wosnitzer, MD, nuclear medicine fellow at St. Luke’s Hospital in New York City. In addition to the scanner cost, many radiolabeled tracers require expensive cyclotrons for production. Since many institutions cannot afford their own cyclotron, delivery of tracers from outside facilities can be problematic given the short physical half-life of some tracers. Regardless of the limitations, the benefits of PET/CT and SPECT/CT far outweigh the costs given their crucial role in both surgical and radiation planning as well as restaging and recurrence of disease, Wosnitzer notes.
The sentinel lymph node biopsy approach remains the most accurate to date to detect non-macroscopic lymph node metastases, and for this SPECT/CT is a valuable technique. Also, further development of radionuclide and fluorescent tracers, as well as dedicated equipment will enhance the accuracy and reliability of sentinel lymph node biopsy.
Mary C. Tierney, MS, Vice President & Chief Content Officer, TriMed Media Group
Mary joined TriMed Media in 2003. She was the founding editor and editorial director of Health Imaging, Cardiovascular Business, Molecular Imaging Insight and CMIO, now known as Clinical Innovation + Technology. Prior to TriMed, Mary was the editorial director of HealthTech Publishing Company, where she had worked since 1991. While there, she oversaw four magazines and related online media, and piloted the launch of two magazines and websites. Mary holds a master’s in journalism from Syracuse University. She lives in East Greenwich, R.I., and when not working, she is usually running around after her family, taking photos or cooking.