Atypical presentation of colorectal carcinoma with sole multiple osteolytic bone metastases: a case report

Abstract Background The incidence of colorectal cancer in persons aged < 50 years has been increasing. The diagnosis of colorectal cancer is not difficult if the patient has typical symptoms; however, diagnosis may be difficult in cases with atypical symptoms and signs. We present here an atypical case of metastatic colorectal cancer with fever and sudden onset paraplegia as the sole manifestations. The patient had multiple osteolytic lesions without gastrointestinal symptoms or signs, which resulted in a diagnostic delay of colorectal cancer. Case presentation A 46-year-old Japanese man was transferred to our hospital for evaluation of fever. He had developed fever 8 weeks previously and had been first admitted to another hospital 5 weeks ago. The patient was initially placed on antibiotics based on the suspicion of a bacterial infection. During the hospital stay, the patient experienced a sudden onset of paralysis and numbness in his both legs. Magnetic resonance imaging showed an epidural mass at the level of Th11, and the patient underwent a laminectomy. Epidural abscess and vertebral osteomyelitis were suspected, and antimicrobial treatment was continued. However, his fever persisted, and he was transferred to our hospital. Chest, abdominal, and pelvic computed tomography (CT) with contrast showed diffusely distributed osteolytic lesions. Fluorodeoxyglucose-positron-emission tomography showed high fluorodeoxyglucose accumulation in multiple discrete bone structures; however, no significant accumulation was observed in the solid organs or lymph nodes. A CT-guided bone biopsy obtained from the left iliac bone confirmed the evidence of metastatic adenocarcinoma based on immunohistochemistry. A subsequent colonoscopy showed a Borrmann type II tumor in the sigmoid colon, which was confirmed to be a poorly differentiated adenocarcinoma. As a result of shared decision-making, the patient chose palliative care. Conclusions Although rare, osteolytic bone metastases as the sole manifestation can occur in patients with colorectal cancer. In patients with conditions difficult to diagnose, physicians should prioritize the necessary tests based on differential diagnoses by analytical clinical reasoning, taking into consideration the patient’s clinical manifestation and the disease epidemiology. Bone biopsies are usually needed in patients only with sole osteolytic bone lesions; however, other rapid and useful non-invasive diagnostic tests can be also useful for narrowing the differential diagnosis.

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Differences in Radiation Exposure of CT-Guided Percutaneous Manual and Powered Drill Bone Biopsy

CardioVascular and Interventional Radiology ◽

10.1007/s00270-021-02851-z ◽

2021 ◽

Author(s):

Sebastian Zensen ◽

Sumitha Selvaretnam ◽

Marcel Opitz ◽

Denise Bos ◽

Johannes Haubold ◽

...

Keyword(s):

Radiation Exposure ◽

Diagnostic Yield ◽

Bone Biopsy ◽

Lumbar Vertebrae ◽

Bone Lesions ◽

Anatomical Location ◽

Thoracic Vertebrae ◽

Level Of Evidence ◽

Ct Guided ◽

Bone Biopsies

Abstract Purpose Apart from the commonly applied manual needle biopsy, CT-guided percutaneous biopsies of bone lesions can be performed with battery-powered drill biopsy systems. Due to assumably different radiation doses and procedural durations, the aim of this study is to examine radiation exposure and establish local diagnostic reference levels (DRLs) of CT-guided bone biopsies of different anatomical regions. Methods In this retrospective study, dose data of 187 patients who underwent CT-guided bone biopsy with a manual or powered drill biopsy system performed at one of three different multi-slice CT were analyzed. Between January 2012 and November 2019, a total of 27 femur (A), 74 ilium (B), 27 sacrum (C), 28 thoracic vertebrae (D) and 31 lumbar vertebrae (E) biopsies were included. Radiation exposure was reported for volume-weighted CT dose index (CTDIvol) and dose–length product (DLP). Results CTDIvol and DLP of manual versus powered drill biopsy were (median, IQR): A: 56.9(41.4–128.5)/66.7(37.6–76.2)mGy, 410(203–683)/303(128–403)mGy·cm, B: 83.5(62.1–128.5)/59.4(46.2–79.8)mGy, 489(322–472)/400(329–695)mGy·cm, C: 97.5(71.6–149.2)/63.1(49.1–83.7)mGy, 627(496–740)/404(316–515)mGy·cm, D: 67.0(40.3–86.6)/39.7(29.9–89.0)mGy, 392(267–596)/207(166–402)mGy·cm and E: 100.1(66.5–162.6)/62.5(48.0–90.0)mGy, 521(385–619)/315(240–452)mGy·cm. Radiation exposure with powered drill was significantly lower for ilium and sacrum, while procedural duration was not increased for any anatomical location. Local DRLs could be depicted as follows (CTDIvol/DLP): A: 91 mGy/522 mGy·cm, B: 90 mGy/530 mGy·cm, C: 116 mGy/740 mGy·cm, D: 87 mGy/578 mGy·cm and E: 115 mGy/546 mGy·cm. The diagnostic yield was 82.4% for manual and 89.4% for powered drill biopsies. Conclusion Use of powered drill bone biopsy systems for CT-guided percutaneous bone biopsies can significantly reduce the radiation burden compared to manual biopsy for specific anatomical locations such as ilium and sacrum and does not increase radiation dose or procedural duration for any of the investigated locations. Level of Evidence Level 3.

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Treatment of bone metastases with dichloromethylene bisphosphonate.

Journal of Clinical Oncology ◽

10.1200/jco.1992.10.4.591 ◽

1992 ◽

Vol 10 (4) ◽

pp. 591-598 ◽

Cited By ~ 19

Author(s):

G Francini ◽

S Gonnelli ◽

R Petrioli ◽

F Conti ◽

P Paffetti ◽

...

Keyword(s):

Bone Metastases ◽

Serum Alkaline Phosphatase ◽

Urinary Calcium ◽

Bone Lesions ◽

Osteolytic Lesions ◽

Concurrent Use ◽

Pathologic Fractures ◽

Group A ◽

Group B

PURPOSE The study was undertaken to evaluate the effects of dichloromethylene bisphosphonate (Cl2MDP) on osteolytic and osteoblastic bone lesions from a variety of tumoral primary sites and to investigate the in vivo mechanism underlying the action of this drug. PATIENTS AND METHODS Seventy-six patients participated in the current study: 59 had predominantly osteolytic lesions and 17 osteoblastic metastases. Sixteen patients had hypercalcemia. All of the patients received 300 mg of Cl2MDP intravenously (IV) for 7 days and then 200 mg of Cl2MDP intramuscularly (IM) for 14 days. Biochemical parameters were measured in the patients before the start of treatment and 3, 7, 14, and 21 days after beginning treatment. After the withdrawal of parenteral Cl2MDP, 59 patients with predominantly osteolytic lesions were then randomized to receive chemotherapy alone (group A, 29 cases) or chemotherapy plus Cl2MDP given at an oral dose of 1,200 mg/d (group B, 30 cases). RESULTS Serum calcium (Ca), urinary calcium (UCa) phosphate (UPO4), and hydroxyproline (HOP) excretion levels significantly decreased in all patients, whereas no significant changes occurred in serum alkaline phosphatase (AlkPh) and bone Gla-protein (BGP) levels. In 56 patients with painful bone lesions, a progressive analgesic effect was observed mainly between day 7 and day 14. In patients with predominantly osteoblastic metastases, the Cl2MDP treatment led to a more evident hypocalcemia and an increase in both AlkPh and BGP. However, in the majority of these patients the hypocalcemia was corrected by the concurrent use of effective cytotoxic treatments capable of reducing osteoblast stimulation. During 6 months of follow-up, two pathologic fractures occurred in patients of group A, and none occurred in patients of group B. CONCLUSIONS We conclude that Cl2MDP was effective in patients presenting bone metastases with and without hypercalcemia. Care should be taken particularly in those patients with mixed metastases when the sclerotic component is predominant, as the drug may enhance the possibility of hypocalcemia, which is generally corrected by effective cytotoxic drugs. Therefore, Cl2MDP can be considered a valuable support in the treatment of bone metastases.

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Detection of PIK3CA Mutations in Breast Cancer Bone Metastases

ISRN Oncology ◽

10.5402/2012/492578 ◽

2012 ◽

Vol 2012 ◽

pp. 1-8

Author(s):

Manijeh Daneshmand ◽

Jennifer E. L. Hanson ◽

Mitra Nabavi ◽

John F. Hilton ◽

Lisa Vandermeer ◽

...

Keyword(s):

Breast Cancer ◽

Bone Marrow ◽

Bone Metastases ◽

Cancer Cells ◽

Primary Tumour ◽

Breast Cancer Patients ◽

Ct Guided ◽

Mutation Status ◽

Bone Biopsies ◽

Metastatic Sites

Background. An important goal of personalized cancer therapy is to tailor specific therapies to the mutational profile of individual patients. However, whole genome sequencing studies have shown that the mutational profiles of cancers evolve over time and often differ between primary and metastatic sites. Activating point mutations in the PIK3CA gene are common in primary breast cancer tumors, but their presence in breast cancer bone metastases has not been assessed previously. Results. Fourteen patients with breast cancer bone metastases were biopsied by three methods: CT-guided bone biopsies; bone marrow trephine biopsies; and bone marrow aspiration. Samples that were positive for cancer cells were obtained from six patients. Three of these patients had detectable PIK3CA mutations in bone marrow cancer cells. Primary tumor samples were available for four of the six patients assessed for PIK3CA status in their bone metastases. For each of these, the PIK3CA mutation status was the same in the primary and metastatic sites. Conclusions. PIK3CA mutations occur frequently in breast cancer bone metastases. The PIK3CA mutation status in bone metastases samples appears to reflect the PIK3CA mutation status in the primary tumour. Breast cancer patients with bone metastases may be candidates for treatment with selective PIK3CA inhibitors.

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P044 Tibia honest, it takes a lot of spine to diagnose DISC

Rheumatology ◽

10.1093/rheumatology/keab247.041 ◽

2021 ◽

Vol 60 (Supplement_1) ◽

Author(s):

Wan Lin Ng ◽

Aqeel Anjum ◽

Joe Devlin ◽

Alexander Fraser

Keyword(s):

Inflammatory Markers ◽

Plasma Cells ◽

Whole Body ◽

Heroin Addiction ◽

Dramatic Improvement ◽

Diagnostic Dilemma ◽

Male Adult ◽

Ct Guided ◽

Osteolytic Lesions ◽

Bone Biopsies

Abstract Background/Aims CRMO is a rare autoinflammatory condition characterised by sterile bone osteolytic lesions which is described mainly in children with a female preponderance. Methods A 31 year-old male presented with a 4-week history of productive cough, abdominal pain, left sided chest pain and right hip pain. He is a smoker with a background of heroin addiction and alcohol abuse. He was homeless and no family history available as he was fostered. His chest radiography was unremarkable but he had inflammatory markers. He was treated for as chest infection and heroin withdrawal. CT abdomen and pelvis demonstrated multiple osteolytic lesions in the pelvis, sternum, thoracic and lumbar spine. His HIV, Quantiferon and blood cultures were negative. His immunoglobulins, urine Bence Jones protein and echocardiogram were normal. In-depth assessment by the Infectious Disease team failed to isolate an infective pathogen. Bone marrow aspirate and trephine were unremarkable. Two CT-guided bone biopsies done twice showed plasma cells and macrophages. His condition deteriorated rapidly over 2 months. He mobility was reduced to wheelchair-bound and had dramatic 10kg weight loss. Results In the absence of an infective or malignant cause, the Rheumatology service was consulted. Having reviewed the extensive data available, he was diagnosed with a likely but unusually aggressive form of adult-onset chronic recurrent multifocal osteomyelitis (CRMO). He was commenced initially on IV methylprednisolone, zoledronic acid, methotrexate and, etoricoxib. Subsequently he was treated with, tocilizumab and teriparatide. Whole body MRI revealed numerous other lesions not evident on previous imaging including lesions of the distal right humerus, proximal right femur and both tibias. His symptoms and inflammatory markers improved substantially over several days following treatment. A repeat full body MRI demonstrated dramatic improvement in the bony lesions. Soon he was able to walk again and gained some weight before he absconded from the hospital. His treatment was changed to tocilizumab infusion and denosumab injection to facilitate compliance. Conclusion This is an unusual fascinating case which posed a significant diagnostic dilemma. Ruling out infection particularly in great challenge in diagnosing CRMO in a male adult who is homeless and a heroin abuser presenting with multifocal osteolytic lesions was challenging. The severity of his condition necessitated using novel treatments such as tocilizumab. Disclosure W. Ng: None. A. Anjum: None. J. Devlin: None. A. Fraser: None.

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A phase II trial of cabozantinib (Cabo) in patients (pts) with castrate-resistant prostate cancer (CRPC) metastatic to bone (NCT01428219).

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.tps5094 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. TPS5094-TPS5094

Author(s):

Petros Grivas ◽

Stephanie Daignault ◽

Kathleen A. Cooney ◽

Jon Jacobson ◽

Corrie Yablon ◽

...

Keyword(s):

Prostate Cancer ◽

Bone Metastases ◽

Bone Metabolism ◽

Phase Ii ◽

Phase Ii Trial ◽

Bone Lesions ◽

Clinical Activity ◽

Type I ◽

Synergistic Activity ◽

Ct Guided

TPS5094 Background: MET overexpression predicts prostate cancer invasion and bone metastasis; inhibition of MET/VEGF pathways has synergistic activity in CRPC (Knudsen et al. Adv Cancer Res 2004; Aftab et al. Clin Transl Oncol 2011). Cabo is a small molecule that inhibits multiple receptor tyrosine kinases, including MET and VEGFR2. A phase II randomized discontinuation trial of Cabo showed clinical activity in CRPC, including reduction of soft tissue lesions, prolongation of progression-free survival (PFS), resolution of bone scans, and reductions in bone turnover markers, pain and narcotic use (Smith et al, JCO 2013). To further define the activity of Cabo in pts with CRPC and bone metastases, we launched a phase II trial to characterize the effects of Cabo on bone metabolism and tumor activity in prostate cancer bone lesions. We hypothesize that the clinical activity of Cabo correlates with measurable pharmacodynamic effects on bone micro-environment. Methods: After informed consent, chemotherapy-naive pts with progressive CRPC and bone metastases accessible to CT-guided biopsy, adequate performance status/organ function, are treated with Cabo 60 mg once daily. Primary endpoint: proportion of pts progression-free (PF) at 12 weeks. Secondary endpoints: safety, PFS, response proportion/duration, PSA response, PSA time-to-progression. A Simon's two-stage mini-max design permits early termination after the first 27 evaluable pts in case of unfavorable results. Alternatively, up to 46 evaluable pts will be accrued. Cabo would not be of interest if the 12-week PF proportion is <0.45; it would be of definite clinical interest if the 12-week PF proportion is >0.65 (5% type I error, 85% power). Perfusion/diffusion-weighted MRI (parametric response maps) and bone lesion biopsies are required at baseline and 6 weeks after starting Cabo. Doxycycline is administered prior to bone biopsy for bone labeling. Bone cores are sent for dynamic histomorphometry and immunohistochemistry (phospho-MET/MET, phospho-VEGFR2/VEGFR2, phospho-Akt/Akt). Serum is collected at several time-points to measure markers of bone metabolism. 13 of 27 first-stage pts have been enrolled and started Cabo. Clinical trial information: NCT01428219.

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Assessment of suspected bone metastases

Acta Radiologica ◽

10.1080/02841859709172431 ◽

1997 ◽

Vol 38 (5) ◽

pp. 890-895 ◽

Cited By ~ 3

Author(s):

I. Çiray ◽

G. Åström ◽

C. Sundström ◽

H. Hagberg ◽

H. Ahlström

Keyword(s):

Bone Metastases ◽

Bone Biopsy ◽

Clinical Information ◽

Benign Lesions ◽

True Negative ◽

Ct Guided ◽

Negative Results ◽

Skeletal Lesion ◽

Bone Biopsies ◽

Malignant Lesions

Purpose: To evaluate the role of CT with and without clinical information as compared to CT-guided bone biopsy in the assessment of suspected bone metastases. Material and Methods: The study comprised 51 consecutive patients with suspected bone metastases who had undergone CT-guided bone biopsies with an eccentric drill system. CT of the targets, clinical information, and histopathology were scored separately as malignant, uncertain or benign. The results of CT alone and CT in combination with clinical information were compared to the results of histopathology. Results: Histopathology diagnosed 45/51 lesions (88%), 23 as malignant and 22 as benign. CT correctly depicted 17 of these 23 malignant lesions. The remaining 6 malignant lesions were CT-scored as uncertain (n=5) or benign (n=l). CT correctly depicted only 3 of the 22 benign lesions. The remaining 19 benign lesions were CT-scored as malignant (n=2) or uncertain (n=17). When uncertain CT scores were combined with clinical scores, the true-positive and true-negative results for malignancy increased from 44% to 82%. Conclusion: In most cases, CT in combination with clinical information gives enough information about the nature — malignant or benign — of a skeletal lesion. In uncertain cases, diagnostic accuracy can be improved by means of CT-guided bone biopsy.

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Multiple Metastasis-Like Bone Lesions in Scintigraphic Imaging

Journal of Biomedicine and Biotechnology ◽

10.1155/2012/957364 ◽

2012 ◽

Vol 2012 ◽

pp. 1-8 ◽

Cited By ~ 6

Author(s):

Ying Zhang ◽

Chunlei Zhao ◽

Hongbiao Liu ◽

Haifeng Hou ◽

Hong Zhang

Keyword(s):

Bone Metastases ◽

Eosinophilic Granuloma ◽

Clinical Work ◽

Whole Body ◽

Bone Lesions ◽

Osteolytic Lesions ◽

Multiple Imaging ◽

Imaging Results ◽

Multiple Bone Metastases ◽

Treatment Procedures

Multiple benign osteolytic lesions are very hard to differentiate from disseminated bone metastasis. Whole-body bone scintigraphy (WBBS) with technetium-99m methylene diphosphonate (Tc-99m MDP) demonstrates multiple lesions with increased uptake in any bone involved. Even combined with medical history and multiple imaging results, such as MRI and CT, the clinical diagnosis of metastasis lesion remains as a challenge. These clinical characteristics are similar to multiple malignant bone metastases and therefore affect the following treatment procedures. In this paper, we analyzed multiple benign osteolytic lesions, like eosinophilic granuloma (EG), multiple myeloma (MM), disseminated tuberculosis, fibrous dysplasia, or enchondroma, occurring in our daily clinical work and concluded that additional attention should be paid before giving the diagnosis of multiple bone metastases.

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Consumption of Lactose, Other FODMAPs and Diarrhoea during Adjuvant 5-Fluorouracil Chemotherapy for Colorectal Cancer

Nutrients ◽

10.3390/nu12020407 ◽

2020 ◽

Vol 12 (2) ◽

pp. 407

Author(s):

Reetta Holma ◽

Reijo Laatikainen ◽

Helena Orell ◽

Heikki Joensuu ◽

Katri Peuhkuri ◽

...

Keyword(s):

Colorectal Cancer ◽

Adjuvant Therapy ◽

Gastrointestinal Symptoms ◽

Mucosal Injury ◽

Dietary Carbohydrates ◽

Food Diary ◽

High Consumption ◽

Increased Risk ◽

Symptom Diary ◽

Low Consumption

Chemotherapy-induced mucosal injury of the small intestine may interfere with the enzymes and transporters responsible for the hydrolysis and absorption of dietary carbohydrates causing diarrhoea, abdominal discomfort and pain. The aim of this study was to investigate the association between the consumption of foods rich in FODMAPs (fermentable oligo-, di- and monosaccharides and polyols) and gastrointestinal symptoms in patients receiving adjuvant therapy for colorectal cancer. The patients (n = 52) filled in a 4-day food diary at baseline and during therapy and kept a symptom diary. The intakes of FODMAP-rich foods were calculated as portions and the intakes were divided into two consumption categories. Patients with high consumption of FODMAP-rich foods had diarrhoea more frequently than those with low consumption (for lactose-rich foods the odds ratio (OR) was 2.63, P = 0.03; and for other FODMAP-rich foods 1.82, P = 0.20). Patients with high consumption of both lactose-rich and other FODMAP-rich foods had an over 4-fold risk of developing diarrhoea as compared to those with low consumption of both (OR, 4.18; P = 0.02). These results were confirmed in multivariate models. Conclusion: Consumption of lactose-rich foods results in an increased risk of diarrhoea during adjuvant therapy for colorectal cancer, especially when the consumption of other FODMAP-rich foods is also high.

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Validity of negative bone biopsy in suspicious bone lesions

Acta Radiologica Open ◽

10.1177/20584601211030662 ◽

2021 ◽

Vol 10 (7) ◽

pp. 205846012110306

Author(s):

Mine B Lange ◽

Lars J Petersen ◽

Michael B Nielsen ◽

Helle D Zacho

Keyword(s):

Bone Biopsy ◽

False Negative ◽

Exclusion Criterion ◽

Bone Lesions ◽

False Negatives ◽

Patient Morbidity ◽

Bone Biopsies ◽

Initial Biopsy ◽

Valid Criterion

Background The presence of malignant cells in bone biopsies is considered gold standard to verify occurrence of cancer, whereas a negative bone biopsy can represent a false negative, with a risk of increasing patient morbidity and mortality and creating misleading conclusions in cancer research. However, a paucity of literature documents the validity of negative bone biopsy as an exclusion criterion for the presence of skeletal malignancies. Purpose To investigate the validity of a negative bone biopsy in bone lesions suspicious of malignancy. Material and Method A retrospective cohort of 215 consecutive targeted non-malignant skeletal biopsies from 207 patients (43% women, 57% men, median age 64, and range 94) representing suspicious focal bone lesions, collected from January 1, 2011, to July 31, 2013, was followed over a 2-year period to examine any additional biopsy, imaging, and clinical follow-up information to categorize the original biopsy as truly benign, malignant, or equivocal. Standard deviations and 95% confidence intervals were calculated. Results 210 of 215 biopsies (98%; 95% CI 0.94–0.99) showed to be truly benign 2 years after initial biopsy. Two biopsies were false negatives (1%; 95% CI 0.001–0.03), and three were equivocal (lack of imaging description). Conclusion Our study documents negative bone biopsy as a valid criterion for the absence of bone metastasis. Since only 28% had a confirmed diagnosis of prior cancer and not all patients received adequately sensitive imaging, our results might not be applicable to all cancer patients with suspicious bone lesions.

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Prostatic Acid Phosphatase Alters the RANKL/OPG System and Induces Osteoblastic Prostate Cancer Bone Metastases

Endocrinology ◽

10.1210/en.2016-1606 ◽

2016 ◽

Vol 157 (12) ◽

pp. 4526-4533 ◽

Cited By ~ 9

Author(s):

Alexander Kirschenbaum ◽

Sudeh Izadmehr ◽

Shen Yao ◽

Kieley L. O’Connor-Chapman ◽

Alan Huang ◽

...

Keyword(s):

Prostate Cancer ◽

Acid Phosphatase ◽

Bone Metastases ◽

Cross Talk ◽

Bone Cells ◽

Bone Mineralization ◽

Critical Role ◽

Prostatic Acid Phosphatase ◽

Bone Lesions ◽

Rankl Expression

Prostate cancer (PCa) is unique in its tendency to produce osteoblastic (OB) bone metastases. There are no existing therapies that specifically target the OB phase that affects 90% of men with bone metastatic disease. Prostatic acid phosphatase (PAP) is secreted by PCa cells in OB metastases and increases OB growth, differentiation, and bone mineralization. The purpose of this study was to investigate whether PAP effects on OB bone metastases are mediated by autocrine and/or paracrine alterations in the receptor activator of nuclear factor κ-B (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG) system. To investigate whether PAP modulated these factors and altered the bone reaction, we knocked down PAP expression in VCaP cells and stably overexpressed PAP in PC3M cells, both derived from human PCa bone metastases. We show that knockdown of PAP in VCaP cells decreased OPG while increasing RANK/RANKL expression. Forced overexpression of PAP in PC3M cells had the inverse effect, increasing OPG while decreasing RANK/RANKL expression. Coculture of PCa cells with MC3T3 preosteoblasts also revealed a role for secretory PAP in OB-PCa cross talk. Reduced PAP expression in VCaP cells decreased MC3T3 proliferation and differentiation and reduced their OPG expression. PAP overexpression in PC3M cells altered the bone phenotype creating OB rather than osteolytic lesions in vivo using an intratibial model. These findings demonstrate that PAP secreted by PCa cells in OB bone metastases increases OPG and plays a critical role in the vicious cross talk between cancer and bone cells. These data suggest that inhibition of secretory PAP may be an effective strategy for PCa OB bone lesions.

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