|Ahead of print publication
The lytic skeletal lesions: A rare presentation of carcinoma prostate on 18F-fluorodeoxyglucose positron emission tomography/computed tomography
Shantanu Pande1, Nihit Mhatre2, Ipsita Dhal3
1 Department of Nuclear Medicine and Molecular Imaging, All India Institutes of Medical Sciences, Nagpur, Maharashtra, India
2 Department of Nuclear Medicine, Tata Memorial Hospital, Dr. E Borges Marg, Parel East, Mumbai, Maharashtra, India
3 Department of Pathology, Homi Bhabha Cancer Hospital and Mahamana Pandit Madanmohan Malaviya Cancer Centre, Sundar Bagiya, BHU Campus, Varanasi, Uttar Pradesh, India
|Date of Submission||22-May-2022|
|Date of Decision||14-Jul-2022|
|Date of Acceptance||15-Jul-2022|
|Date of Web Publication||04-Oct-2022|
Department of Nuclear Medicine and Molecular Imaging, All India Institutes of Medical Sciences, Nagpur - 441 108, Maharashtra
Source of Support: None, Conflict of Interest: None
We describe the 18F-fluorodeoxyglucose positron emission tomography/contrast enhanced computed tomography (FDG PET/CECT) images of a 63-year-old male who complained of back pain and was suspected of multiple myeloma based on magnetic resonance imaging. PET/CECT suggested the FDG avid lesion involving prostate, accompanied by multiple lytic skeletal lesions with no evidence to suggest other possible primary site. A bone marrow biopsy suggested a metastatic adenocarcinoma of primary prostatic origin. Post anti-androgen therapy follow-up FDG PET/CT revealed reductions in the metabolic activities and soft tissue components of most of the metastatic skeletal lesions. These images highlight the possible indication of FDG PET/CT in evaluation of prostatic malignancy in era of 68Ga-PSMA.
Keywords: Anti androgen therapy, FDG petct, lytic skeletal metastases, Prostate carcinoma
|How to cite this URL:|
Pande S, Mhatre N, Dhal I. The lytic skeletal lesions: A rare presentation of carcinoma prostate on 18F-fluorodeoxyglucose positron emission tomography/computed tomography. J Can Res Ther [Epub ahead of print] [cited 2022 Dec 9]. Available from: https://www.cancerjournal.net/preprintarticle.asp?id=357898
| > Introduction|| |
Fluorodeoxyglucose (FDG) is a glucose analog, and most tumors demonstrate increased glucose metabolism because of upregulation of glucose transporter expression and increased hexokinase activity. However, the role of FDG in evaluating prostate carcinoma is somewhat limited because of non-glucose metabolic pathways such as fatty acid metabolism and 68Gallium prostate-specific membrane antigen ligand is increasingly being used. Although serum prostate-specific antigen (PSA) is a sensitive marker, a subset of patients can exhibit normal serum PSA levels even with high-grade prostate cancer. Sclerotic bone metastases are common and lytic bone metastases are rare in prostate carcinoma. In this context, we report a case involving a patient with lytic skeletal lesions with normal serum PSA level (1.79 ng/ml; normal: 0–4 ng/ml), in whom FDG PET/CT results suggested the prostate as a possible primary malignancy site.
| > Case Report|| |
A 63-year-old male presented with complaints of a 2-month history of back pain, weakness in both lower limbs, and difficulty with ambulation for 1 month. Magnetic resonance imaging (MRI) performed elsewhere revealed widespread expansile lesions in the spine and pelvic bones, raising suspicion for multiple myeloma. Clinical examination revealed pedal edema and reduced power in both lower limbs. There were no known co-morbidities, and his rest of medical history was noncontributory. The patient underwent 18F-fluorodeoxyglucose positron emission tomography/(contrast-enhanced) computed tomography (18F-FDG PET/(CE) CT), which revealed focal FDG uptake predominantly in the right peripheral zone of the prostate [Figure 1]b, [Figure 1]c and multiple pelvic nodes. Multiple FDG avid, expansile, and lytic lesions with associated soft tissue were evident throughout the skeleton [Figure 1]a, [Figure 1]b, [Figure 1]c, [Figure 1]d, [Figure 1]e, [Figure 1]f, [Figure 1]g, [Figure 1]h, [Figure 1]i. Bone marrow biopsy revealed marrow infiltration by atypical epithelial cells (arranged in clusters) with occasional acinar patterns [Figure 2]a. On immunohistochemistry (IHC), tumor cells were positive for alpha-methylacyl-CoA racemase (i.e., AMACR, [Figure 2]b) but negative for cytokeratins (CK), CK7, CK20, and CK19 and Thyroid transcription factor-1. The reported sensitivity and specificity of AMACR varies from 80 to 100% for prostate carcinoma. There were no clonal plasm cells detected on bone marrow examination. Hence, the aforesaid findings favored diagnosis of adenocarcinoma of prostatic origin. The urine Bence-Jones protein was negative, no “M” band detected on serum electrophoresis, and free light chain (FLC) ratio was normal. Anemia and hypercalcemia could be overlapping features in these cases. Overall findings suggested a high probability of primary prostatic malignancy associated with unusual metastatic bony lesions. The patient underwent androgen deprivation therapy (degarelix) and bicalutamide. Follow-up FDG PET/CT performed 1 year later revealed complete resolution of focal prostate FDG uptake [Figure 3]d. Compared to initial FDG PET/CT images [Figure 3]a, [Figure 3]b, [Figure 3]e, [Figure 3]f, [Figure 3]i, and [Figure 3]j and [Figure 4]a, [Figure 4]c, and [Figure 4]e, follow-up images showed resolution and reductions of metabolic activities and soft tissue components of most of the metastatic skeletal lesions [Figure 3]c, [Figure 3]d, [Figure 3]g, [Figure 3]h, [Figure 3][Figure 3][Figure 3][Figure 3]k, and [Figure 3]l and [Figure 4]b, [Figure 4]d, and [Figure 4]f, except for a lesion in the left acetabulum exhibiting persistent FDG uptake and soft tissue component [Figure 4]b, [Figure 4]f.
|Figure 1: Maximum intensity projection (a) revealed multiple foci of FDG uptake in visualized body (black arrowheads) (b) axial and (d) sagittal CT images showed enhancing lesion involving prostate (white arrow). Corresponding PET/CT images (c and e) revealed focal FDG uptake in lesion involving prostate. Multiple FDG avid expansile lytic skeletal lesions with associated enhancing soft tissue at various sites (yellow arrowheads in b to i images)|
Click here to view
|Figure 2: (a) Bone marrow biopsy revealed marrow infiltration by atypical epithelial cells in clusters and occasional acinar pattern (b) Immunohistochemistry showed tumor cells positive for alpha-methylacyl-CoA racemase|
Click here to view
|Figure 3: Pre- and post-therapy images of CT and PET/CT. Pre-therapy images (white arrow in a and b) showed focal FDG avid enhancing lesion in prostate that is resolved in post-therapy images (white arrow in c and d). Pre-therapy images (yellow arrowheads in a, b, e, f, i, and j) showed FDG avid expansile lytic lesions with enhancing soft tissue at various sites, corresponding post-therapy images (yellow arrowheads in c, d, g, h, k, and l) showed complete to significant reductions in enhancing soft tissue components and metabolic activity|
Click here to view
|Figure 4: (a) Pre-therapy maximum intensity projection (MIP) image, compared with post-therapy MIP image (b) revealed resolution of majority of skeletal lesions except for lesion in left acetabulum. Pre-therapy sagittal PET/CT image (c) revealed FDG avid skeletal lesions, corresponding post-therapy PET/CT image (d) showed resolution of FDG uptake in skeletal lesions. Pre (e) and post (f) therapy axial CT images showed persistence of soft tissue involving left acetabulum (yellow arrowheads); while there is resolution of soft tissue involving right acetabulum (white arrow)|
Click here to view
| > Discussion|| |
Skeletal lesions, including fibrous dysplasia, eosinophilic granuloma, giant cell tumor, non-ossifying fibroma, aneurysmal bone cyst, hyperparathyroidism (brown tumor), and infection at multiple sites, exhibit osteolytic appearance on imaging scan. Multiple myeloma and metastases from the lung, breast, and thyroid, neuroendocrine tumors, and gastrointestinal malignancies can give rise to osteolytic skeletal lesions. Knowledge of patient age, number of lesions, and lesion site (i.e., diaphysis, metaphysis, and epiphysis) can help to narrow the differentials. In our case, the probability of these skeletal lesions being benign was lower because the above-described benign lesions exhibit peak occurrence in the first and second decade of life, with most lesions presenting before the third decade of life. Although chondromyxoid fibromas, giant cell tumors, fibrosarcoma, and chondrosarcomas are detected in older patients, their presentation is usually a solitary large bony lesion. Matrix calcification, zone of transition, and periosteal reaction are important to differentiate bone tumors, although overlap between benign and malignant skeletal lesion is not uncommon. Considering our patient's age and the number of lesions detected, two main differentials were noted as follows: multiple myeloma and metastases from primary malignancy producing lytic lesions. No lesions were detected using FDG PET/CT in the thyroid, lungs, breast, kidneys, gastrointestinal tract, and hepatobiliary system that could generate lytic metastases (synchronous malignancy). Additionally, there were no complaints suggestive of primary problems in the gastrointestinal system (e.g., abdominal pain and rectal bleeding). Not all the lymph nodes were FDG avid, and liver and spleen showed no focal FDG uptake but extensive FDG avid skeletal lesions making the diagnosis of lymphoma unlikely. The absence of the Bence-Jones protein, no “M” band on serum electrophoresis, and normal FLC along with no plasma cells on marrow biopsy made diagnosis of multiple myeloma less likely. The IHC suggested the origin of bony lesions from malignancy involving the prostate. The presence of multiple skeletal metastases can be explained by “seed and soil hypothesis” though the vertebrae, pelvic bones, and ribs are most commonly involved in carcinoma prostate. Based on overall findings, prostate carcinoma producing lytic bony metastases was the most likely scenario in this case, and was confirmed on follow-up imaging.
The normal prostate generally exhibits a low-grade, homogeneous distribution of FDG. Because the extent of FDG accumulation in patients with benign prostatic hyperplasia, prostatitis, and prostate cancer overlap considerably, it is difficult to reliably differentiate benign from malignant disease., Tumor proximity to physiological bladder activity may compromise accurate tumor identification. For these reasons and, because prostate cancer features non-glucose metabolic pathways, FDG PET/CT is not generally used for initial staging. However, among patients with high serum PSA levels or known aggressive prostate cancer (Gleason score >7), it may be valuable for initial staging. In patients exhibiting biochemical recurrence, FDG PET may be useful in detecting disease. In post-treatment evaluation, it is essential to assess the status of metastatic bony lesions (the most common metastasis sites of prostate cancer). Such lesions are considered to be non-target lesions. The Response Evaluation Criteria in Solid Tumors (RECIST) criteria are structure based. Metabolically based criteria (e.g., PET Response Criteria in Solid Tumors – PERCIST) may be more appropriate and may warrant further exploration using FDG PET/CT in this clinical context. Sclerotic bone metastases are common in patients with prostate cancer and lytic bone metastases are rare. The latter probably reflects overproduction of parathyroid hormone-related peptide(s) by prostate cancer cells. FDG PET/CT has demonstrated low sensitivity in detecting sclerotic metastatic lesions of prostate cancer but useful in detecting lytic skeletal metastases., Although PSA is a sensitive marker for prostate cancer, some patients with high-grade cancers can, nevertheless, exhibit normal PSA values, as in the present case. On follow-up of this case, the serum PSA was found to be 7.0 ng/ml. In summary, FDG PET/CT generally affords only low sensitivity and specificity in terms of prostate cancer detection; however, it is useful in specific clinical scenarios involving the prostate.
In the present case, 18F-FDG PET/CT suggested a likely primary site (i.e., the prostate) in a patient with lytic metastatic skeletal lesions and normal serum PSA level. 18F-FDG PET/CT contributed to monitoring the response to treatment. Therefore, 18F-FDG PET/CT is appropriate in specific clinical scenarios involving the prostate and for evaluation of lesions of unknown origin
The prostate biopsy was not available and the MRI of the pelvis could have been useful; however, the overall disease course suggested that a diagnosis other than carcinoma of the prostate was unlikely.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient (s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initial s will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| > References|| |
Macheda ML, Rogers S, Best JD. Molecular and cellular regulation of glucose transporter (GLUT) proteins in cancer. J Cell Physiol 2005;202:654-62.
Liu Y, Zuckier LS, Ghesani NV. Dominant uptake of fatty acid over glucose by prostate cells: A potential new diagnostic and therapeutic approach. Anticancer Res 2010;30:369-74.
Bois F, Noirot C, Dietemann S, Mainta IC, Zilli T, Garibotto V, et al
. 68Ga-PSMA-11 in prostate cancer: A comprehensive review. Am J Nucl Med Mol Imaging 2020;10:349-74.
Adhyam M, Gupta AK. A review on the clinical utility of PSA in cancer prostate. Indian J SurgOncol 2012;3:120-9.
Jadvar H, Ye W, Groshen S, Conti PS. [F-18]-Fluorodeoxyglucose PET-CT of the normal prostate gland. Ann Nucl Med 2008;22:787-93.
Jadvar H.Imaging evaluation of prostate cancer with 18Ffluorodeoxyglucose PET/CT: Utility and limitations, Eur J Nucl Med Mol Imaging 2013;40:5-10.
Liu IJ, Zafar MB, Lai YH, Segall GM, Terris MK. Fluorodeoxyglucose positron emission tomography studies in diagnosis and staging of clinically organ-confined prostate cancer. Urology 2001;57:108-11.
Schöder H, Herrmann K, Gönen M, Hricka H, Eberhard S, Scardino P, et al
. 2-[18F] Fluoro- 2-deoxyglucose positron emission tomography for the detection of disease in patients with prostate-specific antigen relapse after radical prostatectomy. Clin Cancer Res 2005;11:4761-9.
Jadvar H. Prostate cancer: PET with 18FFDG, 18F- or 11Cacetate, and 18F- or 11Ccholine. J Nucl Med 2011;52:81-9.
Rabbani SA, Gladu J, Harakidas P, Jamison B, Goltzman D. Overproduction of parathyroid hormonerelated peptide results in increased osteolytic skeletal metastasis by prostate cancer cells in vivo. Int J Cancer 1999;80:25764.
Shreve PD, Grossman HB, Gross MD, Wahl RL. Metastatic prostate cancer: Initial findings of PET with 2deoxy2- F18 fluoroDglucose. Radiology 1996;199:7516.
Kara PO, Kara T, Kara GG, Sari O, Sahin O. Comparison of bone scintigraphy and 18FFDG PETCT in a prostate cancer patient with osteolytic bone metastases. Rev Esp Med Nucl 2011;30:946.
Salminen E, Hogg A, Binns D, Frydenberg M, Hicks R. Investigations with FDGPET scanning in prostate cancer show limited value for clinical practice. ActaOncol 2002;41:4259.
Jadvar H. Is there use for FDGPET in prostate cancer? SeminNucl Med 2016;46:5026.
[Figure 1], [Figure 2], [Figure 3], [Figure 4]