Incidence of occult cancer in children presenting with musculoskeletal symptoms: A 10-year survey in a pediatric rheumatology unit

doi:10.1053/sarh.2000.5752

Seminars in Arthritis and Rheumatism

Volume 29, Issue 6, June 2000, Pages 348-359

https://doi.org/10.1053/sarh.2000.5752 Get rights and content

Abstract

Objectives:

To assess the frequency and types of cancer found in children presenting to our Unit with musculoskeletal symptoms over a 10-year period.

Methods:

The medical records of patients with musculoskeletal symptoms and a final diagnosis of cancer were reviewed. In each case age, gender, presenting symptoms, laboratory data, diagnostic procedures, provisional and final diagnoses, and time between clinical onset and correct diagnosis were reviewed.

Results:

An underlying neoplasia was found in 10 of 1,254 patients (<1%) complaining of musculoskeletal symptoms. The types of malignancies found included acute lymphocytic leukemia (ALL) (6 cases), lymphoma (2 cases), neuroblastoma (1 case), and Ewing's sarcoma (1 case). The mean time between disease onset and final diagnosis was 3.2 months. The most common presenting feature was monoarthritis, involving the larger joints such as the elbows, knees or ankles. Juvenile idiopathic arthritis (JIA) was the most frequent provisional diagnosis. In the preliminary hematologic evaluation, eight patients had an increased erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) value. White blood cell (WBC) count was normal in almost all children, with a normal differential count. Lactic dehydrogenase (LDH) was raised in all children. Bone marrow aspirates and lymph node or bone biopsies were necessary to reach the final diagnosis.

Conclusions:

A malignancy should always be excluded in children with musculoskeletalsymptoms, especially when the clinical pattern is not characteristic of a specific rheumatic disease. Routine laboratory tests may be misleading. The simultaneous presence of high LDH or α-hydroxybutyric dehydrogenase (α-HBDH) levels and raised ESR or CRP, even with normal blood cell counts, should lead to additional investigations.

Relevance:

All patients presenting with arthritis or other musculoskeletal symptoms should have a thorough clinical examination. Disproportionate pain levels and an atypical pattern of “arthritis,” especially in the presence of systemic manifestations, suggest a possible underlying malignancy.

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Development and Initial Validation of the ONCOREUM Score to Differentiate Childhood Cancer with Arthropathy from Juvenile Idiopathic Arthritis
2023, Journal of Pediatrics
To develop and validate a weighted score, the ONCOREUM score, that aids physicians in differentiation of cancer with arthropathy from juvenile idiopathic arthritis (JIA).
Data were extracted from the ONCOREUM Study, a multicenter, cross-sectional investigation aimed at comparing children with cancer and arthropathy to children with JIA. Three statistical approaches were applied to develop the ONCOREUM score and assess the role of each variable in the diagnosis of cancer with arthropathy, including 2 approaches based on multivariable stepwise selection (models 1 and 2) and 1 approach on a Bayesian model averaging method (model 3). The β coefficients estimated in the models were used to assign score points. Considering that not missing a child with cancer is a mandatory clinical objective, discriminating performance was assessed by fixing sensitivity at 100%. Score performance was evaluated in both developmental and validation samples (representing 80% and 20% of the study population, respectively).
Patients with cancer and arthropathy (49 with solid tumors and 46 with hematologic malignancies without peripheral blasts) and 677 patients with JIA were included. The highest area under the receiver operating characteristic (ROC) curve (AUC) in the validation data set was yielded by model 1, which was selected to constitute the ONCOREUM score. The score ranged from −18 to 21.8, and the optimal cutoff obtained through ROC analysis was −6. The sensitivity, specificity, and AUC of the cutoff in the validation sample were 100%, 70%, and 0.85, respectively.
The ONCOREUM score is a powerful and easily applicable tool that may facilitate early differentiation of malignancies with articular complaints from JIA.
Musculoskeletal Diagnoses before Cancer in Children: A Danish Registry-Based Cohort Study
2022, Journal of Pediatrics
To identify the prevalence of musculoskeletal diagnoses recorded 6 months before the diagnosis of cancer and to evaluate whether preceding musculoskeletal diagnoses affected survival.
We performed a nationwide registry-based cohort study including all children under 15 years of age diagnosed with cancer in Denmark over a 23-year period (1996-2018). The Danish National Patient Registry was used to identify musculoskeletal diagnoses and associated dates recorded within 6 months preceding the diagnosis of cancer. We compared the characteristics of children with and without a prior musculoskeletal diagnoses using prevalence ratios and 95% CI and diagnostic interval as median with IQR. We compared survival using Kaplan-Meier and Cox proportional hazards regression analysis adjusting for age, sex, and presence of metastasis at diagnosis.
Of 3895 children with all types of cancer, 264 (7%) had a total of 451 hospital visits with musculoskeletal diagnosis within 6 months preceding the diagnosis of cancer; however, survival was not affected. The overall median diagnostic interval from first musculoskeletal diagnosis (within 6 months before cancer diagnosis) to cancer diagnosis was 15 days (IQR, 7-47 days). A diagnosis of juvenile idiopathic arthritis, unspecified arthritis, and arthropathy each accounted for 5% of the contacts, primarily in children with acute lymphoblastic leukemia, bone sarcomas, or neuroblastomas.
A preliminary musculoskeletal diagnosis occurred in 7% of children with cancer, but did not affect the overall survival.
Musculoskeletal manifestations of childhood cancer and differential diagnosis with juvenile idiopathic arthritis (ONCOREUM): a multicentre, cross-sectional study
2021, The Lancet Rheumatology
Presenting symptoms of childhood cancers might mimic those of rheumatic diseases. However, the evidence available to guide differential diagnosis remains scarce. Preventing wrong or delayed diagnosis is therefore important to avoid incorrect administration of glucocorticoid or immunosuppressive therapy and worsening of prognosis. As such, we aimed to assess the prevalence and characteristics of presenting musculoskeletal manifestations in patients at cancer onset and to identify the factors that differentiate childhood malignancies with arthropathy from juvenile idiopathic arthritis.
We did a multicentre, cross-sectional study at 25 paediatric haemato-oncology centres and 22 paediatric rheumatology centres in Italy. We prospectively recruited patients who were younger than 16 years that were newly diagnosed with cancer or juvenile idiopathic arthritis. We excluded patients with glucocorticoid pre-treatment (>1 mg/kg per day of oral prednisone or equivalent for ≥2 consecutive weeks). We collected data for patients with a new diagnosis of cancer or juvenile idiopathic arthritis using an electronic case report form on a web-based platform powered by the Cineca Interuniversity Consortium. The primary outcome was to describe the frequency and characteristics of musculoskeletal manifestations at cancer onset; and the secondary outcome was to identify factors that could discriminate malignancies presenting with arthropathy, with or without other musculoskeletal symptoms, from juvenile idiopathic arthritis using multivariable logistic regression analysis.
Between May 1, 2015, and May 31, 2018, 1957 patients were eligible, of which 1277 (65%) had cancer and 680 (35%) had juvenile idiopathic arthritis. Musculoskeletal symptoms occurred in 324 (25% [95% CI 23·0–27·8]) of 1277 patients with cancer, of whom 207 had arthropathy. Patients with malignant bone tumours had the highest frequency of musculoskeletal symptoms (53 [80%] of 66), followed by patients with Langerhans histiocytosis (16 [47%] of 34), leukaemia (189 [32%] of 582), soft-tissue sarcomas (16 [24%] of 68), and neuroblastoma (21 [19%] of 109). In the 324 patients with cancer and musculoskeletal symptoms, the most common complaints were joint pain (199 [61%]), followed by limb bone pain (112 [35%]). Joint involvement had a prevalent monoarticular pattern (100 [48%] of 207) and oligoarticular pattern (86 [42%] had 2–4 joints involved and 20 [10%] had >4 joints involved), with the most frequently involved joints being the hip (88 [43%] of 207) and knee (81 [39%]). On multivariable analysis, limb bone pain was the independent variable most strongly associated with cancer (odds ratio [OR] 87·80 [95% CI 18·89–408·12]), followed by weight loss (59·88 [6·34–565·53]), thrombocytopenia (12·67 [2·40–66·92]), monoarticular involvement (11·30 [4·09–31·19]), hip involvement (3·30 [1·13–9·61]), and male sex (2·40 [1·03–5·58]). Factors independently associated with juvenile idiopathic arthritis were morning stiffness (OR 0·04 [95% CI 0·01–0·20]), joint swelling (0·03 [0·01–0·09]), and involvement of the small hand joints (0·02 [0–1·05]).
Our study provides detailed information about presenting musculoskeletal manifestations of childhood cancers and highlights the clinical and laboratory features that are most helpful in the differential diagnosis with juvenile idiopathic arthritis.
Associazione Lorenzo Risolo.
Neuroblastoma metastasis to bone requiring differentiation from septic arthritis of the hip. Report of 2 cases
2018, Journal of Orthopaedic Science
Citation Excerpt :
When non-specific symptoms, such as limping, were included, the proportion of patients presenting with orthopedic symptoms increased to 18%. According to one report, presentation to an orthopedic surgeon first because of orthopedic-related symptoms delayed the diagnosis of neuroblastoma by an average of three months [5]. Therefore, orthopedic surgeons treating children must be aware that patients with neuroblastoma could first present to their service, and neuroblastoma should be included in the differential diagnosis of pain and limping in children.
The Approach to the Child with Joint Complaints
2018, Pediatric Clinics of North America
Citation Excerpt :
Although articular or periarticular pain as the presenting sign of malignancy is uncommon, it should always be included in the differential diagnosis, particularly if the pain is severe. Although there are isolated case reports of intermittent pain, it is more frequently experienced as a constant pain throughout the day and night and can be severe enough to wake the patient from sleep.18–20 The arthritis can involve any number of joints, which most commonly are the large joints; that is, knee, ankle, shoulder, and elbow.
Signs and symptoms of rheumatic diseases as first manifestation of pediatric cancer: diagnosis and prognosis implications
2017, Revista Brasileira de Reumatologia
Avaliar a prevalência e descrever as principais manifestações clínicas, os exames complementares, o tratamento e a evolução de crianças com doenças neoplásicas atendidas inicialmente em um serviço terciário de reumatologia pediátrica.
Analisamos retrospectivamente o prontuário médico de pacientes com diagnóstico definitivo de neoplasia, identificados entre 250 casos novos atendidos no ambulatório de reumatologia pediátrica do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto‐USP, de julho de 2013 a julho de 2015.
Dos 250 pacientes, cinco (2%) tiveram diagnóstico de neoplasia. Desses, 80% apresentavam sintomas constitucionais, principalmente perda de peso e astenia e 60% artrite. Inicialmente, todos apresentavam pelo menos uma série alterada no hemograma, 80% aumento da desidrogenase lática (LDH) e 60% mielograma confirmatório. Dois pacientes necessitaram de biópsia, óssea e de intestino, para o diagnóstico final. Artrite idiopática juvenil foi o diagnóstico inicial mais frequente. Os diagnósticos definitivos foram leucemia linfoide aguda (dois casos), leucemia mieloide aguda‐M3, neuroblastoma e linfoma (um caso cada). Dos pacientes estudados, três (60%) estão em remissão. Dois pacientes foram a óbito (40%), um deles com uso prévio de corticoide.
Os sintomas constitucionais e musculoesqueléticos comuns às doenças reumáticas e neoplásicas podem retardar o diagnóstico e consequentemente agravar o prognóstico das neoplasias. O hemograma inicial, assim como o mielograma, podem estar normais no quadro inicial das neoplasias. Dessa forma, o seguimento clínico evolutivo desses casos torna‐se imperativo e o tratamento, principalmente com corticoides, deve ser retardado até definição diagnóstica.
To assess the prevalence and describe the clinical, laboratory and radiological findings, treatment and outcome of children with cancer initially referred to a tertiary outpatient pediatric rheumatology clinic.
Retrospective analysis of medical records from patients identified in a list of 250 new patients attending the tertiary Pediatric Rheumatology Clinic, Ribeirão Preto Medical School hospital, University of São Paulo, from July 2013 to July 2015, whose final diagnosis was cancer.
Of 250 patients seen during the study period, 5 (2%) had a cancer diagnosis. Among them, 80% had constitutional symptoms, especially weight loss and asthenia, and 60% had arthritis. Initially, all patients had at least one alteration in their blood count, lactate dehydrogenase (LDH) was increased in 80% and a bone marrow smear was conclusive in 60% of patients. Bone and intestine biopsies were necessary for the diagnosis in 2 patients. JIA was the most common initial diagnosis. The definitive diagnosis was acute lymphoblastic leukemia (2 patients), M3 acute myeloid leukemia, lymphoma, and neuroblastoma (one case each). Of 5 patients studied, 3 (60%) are in remission and 2 (40%) died, one of them with prior use of steroids.
The constitutional and musculoskeletal symptoms common to rheumatic and neoplastic diseases can delay the diagnosis and consequently worsen the prognosis of neoplasms. Initial blood count and bone marrow smear may be normal in the initial framework of neoplasms. Thus, the clinical follow‐up of these cases becomes imperative and the treatment, mainly with corticosteroids, should be delayed until diagnostic definition.

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Incidence of occult cancer in children presenting with musculoskeletal symptoms: A 10-year survey in a pediatric rheumatology unit

Abstract

Objectives:

Methods:

Results:

Conclusions:

Relevance:

Semin Arthritis Rheum

J Pediatr

J Pediatr

Semin Arthritis Rheum

J Pediatr

J Pediatr

J Pediatr

Rheumatic manifestations of occult cancer

Cancer

The association of malignancy with rheumatic and connective tissue diseases

Semin Oncol

Rheumatologic manifestations of malignancy

Curr Opin Rheumatol

Rheumatic manifestations of malignancy

Curr Opin Rheumatol

Rheumatic manifestations of neoplasia

Curr Op Rheumatol

Rheumatologic manifestations of cancer

Med Clin North Am

The discriminating value of serum lactate dehydrogenase levels in children with malignant neoplasms presenting as joint pain

Arch Pediatr Adolesc Med