Keywords
Lymphoma - papillary thyroid carcinoma - pediatric cancer - thyroid carcinoma - tuberculosis
INTRODUCTION
Cancer in children is rare, and thyroid carcinoma represents less than 3% of all pediatric
malignancies.[1] Papillary thyroid carcinoma is the most common type and its incidence appears to
rise in the last four decades, which is related to better detection and accurate diagnosis.
Most cases arise during teenage years. Possible risk factors include radiation exposure,
iodine deficiency, previous history of Hashimoto’s thyroiditis, and certain inherited
syndromes.[2] The modality of therapy is extrapolated from adult diseases, as patients undergo
surgical excision with further adjuvant radioactive iodine for non-resectable lesions.
Targeted kinase inhibitors provide a promising option in refractory disease.[3]
Children with PTC typically manifest with an asymptomatic neck mass with or without
lymphadenopathy. Associated dyspnea is common, and some patients have an associated
hyperthyroidism. Fine needle aspiration of the neck mass is very helpful in establishing
the diagnosis, as cytologic features of PTC are easy and can be achieved by simple
sedation in children. The presence of B-symptoms in pediatric PTC is unusual and would
provisionally warrant an alternative diagnosis such as infections or lymphoma.
CASE REPORT
In June 2014, a 5-year-old boy presented with a 2-month history of fever, night sweats,
weight loss, and cough. Physical examination revealed bilateral anterior cervical
lymph nodes enlargement which were fixed and painless. The patient also had peripheral
cyanosis in digits. Complete blood count test showed hemoglobin concentration: 128
g/L, white blood cell count: 9.12×109/L (30.1% neutrophils, 57.3% lymphocytes, 6.61% eosinophils, 4.54% monocytes, 1.45%
basophils) and platelet count: 329×109/L. Liver enzymes, serum bilirubin, creatinine, and blood urea nitrogen were all normal.
Blood culture showed no bacterial growth.
Chest X-ray revealed bilateral airway narrowing. Neck computed tomography (CT) scan
showed multiple bilateral anterior cervical as well as supraclavicular and infraclavicular
lymphadenopathy causing mass effect. The largest lymph node measured was 20 × 15 mm.
Some lymph nodes showed cystic degeneration suggestive of central necrosis. The thyroid
gland exhibited heterogenous density. CT scan of the chest demonstrated bilateral
nodular and micronodular lung densities and hilar lymphadenopathy [Figures 1],[2],[3]. Abdominal CT scan showed mild hepatomegaly and paraaortic lymph node enlargement.
The overall clinical impression was favoring either tuberculosis or Hodgkin’s lymphoma
(HL).
Figure 1: Neck CT without contrast showing diffuse thyroid enlargement, bilateral lymphadenopathy,
and compression to trachea
Figure 2: Chest HRCT scan showing innumerable micronodules in both lungs of miliary pattern
of dissemination
Figure 3: Chest-X-ray (posterioanterior and lateral views) showing diffuse bilateral miliary
nodular opacities
Based on the clinical suspicion of lymphoma, an excisional biopsy of a single cervical
lymph node was performed. A bone marrow trephine biopsy was also obtained for staging.
Histopathological examination of the lymph node showed proliferation of malignant
thyroid glands, demonstrating papillary growth and characteristic nuclear clearing
and grooves of follicular epithelial cells. Only a residual rim of lymph node tissue
was present [Figures 4],[5],[6]. The diagnosis of metastatic papillary thyroid carcinoma was established. The bone
marrow biopsy was negative for metastasis. The patient was in clinical stage-I disease.
Figure 4: Cervical lymph node excision: low-power view showing a residual rim of lymphoid tissue
(top) and presence of thyroid glands (below)
Figure 5: Medium power view: follicular epithelial cells are arranged in papillae harboring
fibrovascular cores, most notably on the left side of this view
Figure 6: High power view: follicular epithelial cells show prominent nuclear clearing “Orphan
Anne” and occasional nuclear grooves, characteristic of papillary thyroid carcinoma
The patient was transferred to another facility and had total thyroidectomy and cervical
lymph nodes excision. Then he received radioactive iodine therapy. The patient remained
in complete remission until December 2019 when he developed respiratory symptoms.
CT scan revealed multiple bilateral pulmonary nodules consistent with metastasis.
The patient had many admissions to the intensive care unit for unstable vital signs.
He died in March 2020 of septicemia by methicillin-resistant Staphylococcus aureus.
DISCUSSION
Pediatric PTC remains an uncommon disease despite recent annual increase in incidence.
The disease is more common in females and only one-third of the patients are younger
than 12 years. PTC in children and adolescents represents a biologically and molecularly
distinct disease that is different from adults counterpart. For example, BRAF genetic
mutation is very rare in pediatric PTC, while expression of sodium-iodide transporter
in metastatic foci is common compared with adults.[2],[4] The traditional prognostic variables of sex, disease stage, relapse, and histologic
subtype do not have a similar impact on outcome as in adult disease. When the disease
arises in adolescents, the outcome is comparable to adults. However, PTC in prepubertal
age shows inferior prognosis.[5]
The identification of a thyroid nodule in adults is common and harbors a low incidence
of malignancy. In contrast, children rarely develop thyroid nodules, and the chance
of malignancy is as high as a quarter of cases.[2] Clinical features suggestive of malignancy are, if the nodule is large and hard,
adherent to neck structures or associated with lymphadenopathy. Given the small size
of thyroid gland in children, pediatric PTC tends to have larger size, greater chance
of invasion to adjacent structures, and distant metastasis compared with adults. The
rate of recurrence is also high.[1]
The constellation of fever, night sweats, and unintentional weight loss, which are
referred to as B-symptoms, are characteristics of certain diseases that are primarily
chronic and have an inflammatory nature. Prolonged fever is alarming for an infectious
or neoplastic disease. Neoplastic fever is commonly non-infectious and occurs secondary
to elevated cytokines levels. Mutant genes in neoplastic cells are responsible for
aberrant release of cytokines. In addition, tumor-induced inflammation, tissue damage,
and deep vein thrombosis would promote this condition. High levels of cytokines induce
prostacyclin release which directly affects hypothalamus to change its thermostatic
function.[6]
HL is the most common type of lymphoma in children.[7] It primarily affects cervical lymph nodes and spreads contiguously to mediastinal
lymph nodes, causing dyspnea and cough.[8] Approximately 25% of the HL patients suffer from B-symptoms secondary to high level
of interleukin-6.[6] In addition, infection with tuberculosis would cause respiratory symptoms, fever,
and commonly cervical lymphadenopathy. Thus, the symptoms of the patient we present
would strongly match with both diseases.
In addition to lymphoma, B-symptoms were described in several hematologic and solid
tumors such as acute leukemia, renal cell carcinoma, hepatocellular carcinoma, ovarian
cancers, and glioblastoma multiforme.[6] The emergence of B-symptoms in pediatric PTC is exceptionally rare and, to the best
of our knowledge, was not described previously. Despite the presence of respiratory
symptoms, no definite infectious cause was identified and B-symptoms disappeared after
surgical intervention.
CONCLUSION
This case demonstrates the need to consider PTC in the differential diagnosis of children
presenting with neck mass and fever, despite its rare incidence. It also highlights
the important role of histopathologic evaluation to reach the correct diagnosis.
