Tumori maligne primare cu localizare abdominală la copii (neuroblastom și nefroblastom) – prezentare de caz clinic și analiză a literaturii de specialitate

1. Introduction

Primary malignant tumors with multiple localization are insufficiently discussed in modern pediatric oncology. Statistics regarding these nosologies are sporadic. Recent research reveals that the presence of two or more independent malignant tumor formations in a single patient and diagnosed simultaneously or sequentially are called multiple primary tumors (MPT), and each tumor does not show an extension, or recurrence, or metastasis of the other. According to the classification, multiple primary malignant tumors are subdivided, according to their onset, into synchronous and metachronous. The term synchronous tumor is used when the second tumor formation is detected within six months of the diagnosis of the first tumor formation or when both formations are diagnosed in parallel. Special investigations will differentiate multiple primary tumors from multifocal/multicentric, bilateral and systemic ones. Multicentric tumors present multiple tumor conditions located in one organ and with identical histological characteristics. Bilateral tumors are detected in paired organs, and have identical histological characteristics. Systemic tumors develop at various levels of a system or organs, while multiple primary malignant tumors develop in parallel or gradually independently, or one after another within the limits of an organ, or in several organs of a patient, but with identical or diverse histological characteristics, in one and the same organ.

In 1793, the American physician J. Pearson first reported a clinical case of a patient who presented multiple primary malignant tumors (polyneoplasia), such as breast and uterine tumors. In 1889, T. Billroth reported over 30 clinical cases of multiple primary tumors, and he defined multiple primary tumors by publishing their characteristics:

1. the tumors must be located in different organs

2. the tumors must have diverse histological cha­rac­te­ristics

3. each tumor may have its own metastases.

In 1932, Warren and Gates reported diagnostic features of multiple primary malignant tumors^(1,2). Each tumor presents different histological characteristics and excludes the possibility of the same metastasis^(3,4). The given clinical case reports the presence of two primary malignant tumors – adrenal neuroblastoma and renal nephroblastoma.

2. Case report

We report the case of a male patient, aged 3 years and 6 months old, who presented the onset of the disease on 10 February 2023, when he became febrile, associated loss of appetite, fatigue when walking, cough upon physical exertion, pale skin, and fecal masses with a “clay” appearance. The mother observed the presence of an abdominal tumor formation. According to the mother, at the age of 1 year old, the child presented a “fishy” odor from the genitals, along with frequent but painless urination. The child was admitted to the “Academician Natalia Gheorghiu” National Scientific and Practical Center for Pediatric Surgery (IMSP), with the diagnosis of abdominal tumor. On physical examination, the abdomen was enlarged, asymmetrical, bulging in the hypochondrium region where a round tumor formation was palpated, of hard-elastic consistency, poorly mobile, painful on palpation, occupying the entire region of the costal margin on the right side, extending below the navel.

2.1. Initial laboratory data

Blood group A(II), Rh-factor positive. Hemoleucogram: hemoglobin – 90 g/L, erythrocytes 3.5x10⁶/L, leukocytes 9.7x10⁹/L, color index 0.9, non-segmented 6%, segmented 41%, eosinophils 7%, lymphocytes 41%, monocytes 5%; ESR 35mm/hour, platelet count 400x10⁹/L, clotting time 5’15" -5'40"; ALT 14.9 U/L, AST 23.2 U/L, bilirubin 8-0.5-7.5 µmol/L, creatinine 44 µmol/L, glucose 4.29 µmol/L, LDH 630 U/L, urea 21 mg/dL, fibrinogen 5.105 g/L, prothrombin 69.9%, a-fetoprotein 24.1 ng/mL, CRP 58.6 mg/L.

Biological investigations showed first-grade anemia and increased ESR – which are characteristic data for neuroblastoma. An increased a-fetoprotein is suggestive for the presence of tumor formation. The absence of the Cesnic sign does not exclude the presence of metastases in the liver, which occur in neuroblastoma. Increased C-reactive protein indicates the presence of an inflammatory process and/or necrosis of the tumor formation.

2.2. Primary imagistic evaluation

The abdominal computed tomography examination with angiography performed in February 2023 indicated a tumor formation in the right kidney, with blurred contours, with dimensions of approximately 14x13 cm and a density of 20-40 UH. The tumor formation captured the contrast substance unevenly, with an inhomogeneous structure. This tumor formation displaced neighboring organs to the left. The liver was not enlarged; the parenchyma was homogeneous. The gallbladder was not enlarged in size, with a density of 45 UH. The spleen parenchyma was homogeneous. The pancreas was not enlarged, homogeneous, with a lobulated structure. The parenchyma had a density of 22-28 UH. The Wirsung duct was not determined on the trajectory. The adrenal glands were without pathological changes. The left kidney had regular shape, located in a typical place. The left calyceal-pelvic system was without pathological changes. The bilateral ureters were not dilated. The urinary bladder was without pathological changes. Free fluid in the abdominal cavity was not detected. Conclusion: renal tumor on the right – nephroblastoma?

2.3. Evaluation upon admission to the surgery department

The child was consulted jointly with a urologist and an oncopediatrician, and the decision was made to transfer the child to the oncopediatric department for polychemotherapy. After three courses of polychemotherapy, the child was readmitted to our clinic for surgery. Upon admission, the child’s general condition was serious, he had complaints, he had an abdominal tumor, along with periodic, moderate abdominal pain, subfibrillation, loss of appetite, fatigue and pale skin. On objective examination, the abdomen was oval in shape, not distended, without muscle defenses, soft, accessible to palpation, and the tumor was not palpable.

2.3.1. Biological investigations

Hemoglobin 124 g/L, erythrocytes 4.2x10⁶/L, hematocrit 40.2%, leukocytes 9.63x 10⁹/L, neutrophils 35.7%, basophils 0.9%, eosinophils 0.1%, lymphocytes 46.6%, monocytes 16.7%, ESR 10 mm/h, platelets 550x10⁹/L, ALT 16.8 U/L, AST 30.2 U/L, albumin 48.2 g/L, bilirubin 6.7-0.3-6.4 µmol/L, calcium 2.48 mmol/L, chloride 105.1 mmol/L, creatinine 48 µmol/L, urea 3.6, magnesium 0.85 mmol/L, potassium 5.21 mmol/L, sodium 143 mmol/L, total protein 76.7 g/L, APTT 28 s, fibrinogen 3.217 g/L, prothrombin 76.2%.

General urine analysis: quantity – 50 mL, color yellow, density –1016, flat epithelium – 1-2, unmodified erythrocytes – 1-2, leukocytes – 2-4, mucosities – 2+, negative protein. Reaction: acid. Transparency: transparent.

2.3.2. Imagistic evaluation

Abdominal ultrasound revealed a solid tumor formation located in the projection of the upper pole of the right kidney and the adrenal gland on the right, with dimensions of 111x85 mm, with inhomogeneous consistency and overlapping the right lobe of the liver. Liver right lobe: 86 mm, left lobe: 35 mm, with clear contour, homogeneous parenchyma, medium echogenicity, portal vein: 5 mm, gallbladder: 48x7 mm, pancreas: 7x6x8 mm, with regular contour, homogeneous parenchyma, medium echogenicity, spleen: 70 mm, homogeneous, right kidney: 78x33 mm, left kidney: 74x28 mm, parenchyma: 11 mm bilaterally.

Spiral computed tomography with three-dimensional image of the abdomen with contrast on the 80 Slices spiral device:

Retroperitoneally on the right, a massive solid-hypodense volume formation is determined, reported to the T8-L3 vertebral level, of polygonal configuration, well-defined, approximately sized 11.8 cm (vertical) x 8.4 cm (transverse) x 7.4 cm (anteroposterior), with heterogeneous structure – with marking of multiple massive necrolytic areas with a tendency to confluence, predominantly visualized in the venous phase and late phase. Native density of the tissue component +18 UH – +32 UH, post-contrast in the arterial phase +29 UH, in the venous phase +36 UH, late phase +44 UH, with extension to the upper pole of the right kidney and on the posterior parenchymal surface. Vascularized from an aberrant vessel emerging from the abdominal aorta, measuring 1.9 mm (possibly, the right adrenal artery), cranially with 9 mm of the right renal artery. Delimitations: superiorly, the dome of the diaphragm – minimally displaced cranially; anteriorly, by the posterior segments of the right lobe of the liver and the posterior surface of the inferior vena cava; laterally and posteriorly, by the regional costal surface and the retroperitoneal space; medially, the compressed psoas major muscle (tumor invasion is not excluded). Signs of inflammation in the Zuckerkandl fascia; adrenal gland on the right – impossible to appreciate. Massive mass effect on the posterior segments of the right lobe of the liver, by anterior displacement, marked displacement of the right kidney caudal – located at the level of the iliac spine, marked anterior displacement of the inferior vena cava; deformation of the portal vein; compression of the psoas major muscle on the right and compression of the intestinal loops and adjacent organs and the diaphragm on the right.

Abdominal aorta without signs of displacement, superior mesenteric artery, celiac trunk – minimally displaced to the left, due to the aforementioned mass effect. Signs of filling defects – not determined. In the late phase, on the right – the pyelocaliceal system minimally deformed at the upper pole, the pelvis and ureter without signs of compression; on the left, without pathological changes; bilateral ureters – visualized, normally sized (within the limits of the scan).

The rest of the kidneys: on the right – 6.5 cm, on the left – 7.1 cm, homogeneous parenchyma, corticomedullary distinction respected. Renal arteries: on the right, 3 mm; on the left, 4 mm, with a usual course. Adrenal gland on the left – without pathological changes. Single mesenteric lymph nodes, with a maximum short axis diameter of up to 0.8 cm, of round and ovoid configuration, native density +40 UH, post-contrast +60 UH; without signs of mass effect.

Free fluid in the abdominal cavity is not determined.

The rest of the abdominal organs – without pathological changes.

The basal segments – without pathological changes.

The bone structures – intact.

Conclusion: CT imaging data suggestive for the presence of a massive hypodense solid retroperitoneal tumor mass on the right (taking into account the reduction in size of the aforementioned tumor mass, is neuroblastoma of the adrenal gland on the right not excluded?). Subcentimeter mesenteric lymphadenopathy – is it not excluded from secondary genesis?

Taking into account the data from the previous examinations, abdominal MRI with angiography was also performed: massive volume formation (12x7x7 cm) with heterogeneous solid component, peripheral solid, central cyst/fluid, heterogeneous contrast, with clear contour, and mass effect compression of the right lobe of the liver and right kidney. Kidney of normal size. Normal corticomedullary ratio. Upper tracts are not dilated, with typical depression, left adrenal gland of usual size, structure and signal are homogeneous. There is no free fluid in the abdominal cavity. There is no evidence of lymphadenopathy. Ovoid mesenteric lymph nodes up to 6 mm. Conclusion: massive volume formation of the adrenal gland on the right (neuroblastoma).

After intensive preoperative preparation, the child underwent surgery under orotracheal anesthesia. In the supine position, after processing the surgical field through the upper median laparotomy, the abdominal cavity was opened and, during the revision, a tumor formation located retroperitoneally on the right was detected. The retroperitoneal space was opened, where a tumor formation with a concretion in the upper pole of the right kidney was detected. By the blunt and electroshock method, the tumor formation and the adrenal gland on the right were removed with marginal resection of the right kidney – the visible area of the concretion, with renal raphy. Control of hemostasis. Restoration of anatomical plans.

Postoperatively, the child underwent conservative treatment.

Histopathological examination: the morphological peculiarities attested in the tumor formation support conclusive data of the presence of a heterogeneous tissue-cellular neoplasm in varied differentiation of the synchronous characteristics of triphasic nephroblastoma and neuroblastoma, with rich Svaniana-type stroma, diverse mitotic activity, and necrotic pseudo- and myxomatous changes.

3. Discussion

Neuroblastoma and nephroblastoma are the most common abdominal tumors in children. Both are embryonal tumors. This type of tumor is characterized by the proliferation of immature cells that are usually present in the developing embryo. In the embryonic stage, these cells remain immature and then begin to grow uncontrollably, forming a multitude of small immature cells.

Studies in the field reveal that both neuroblastoma and nephroblastoma are the most common tumors diagnosed in children with palpable abdominal tumor formations (“abdominal masses”) that may involve the kidneys.

Neuroblastoma is most often detected in children under 1 year of age, being extremely rare in those older than 5. In 95% of cases, nephroblastoma is the most common neoplasm in children under 15 years of age. The maximum incidence of nephroblastoma is between the ages of 2 and 4 years old, and in 95% of cases, it is diagnosed by the age of 5 years old.

The differential diagnosis between neuroblastoma, nephroblastoma and other renal tumors is based on the patient’s age, clinical manifestations, laboratory and imaging findings. In some cases, imaging features are common to various tumors, making the preoperative diagnosis difficult⁽⁶⁾.

4. Conclusions

1. The case presented is one of the rare cases that require not only an early diagnosis but also a meticulous surgical technique in optimal conditions, with the excision of all tumor elements.

2. Multiple primary malignant tumors are rare conditions in children. The tumors are of moderate size, but involve multiple organs.

3. The diagnosis is difficult, despite the multiple imaging investigations possible and more or less available.

4. Surgery has an important role in the treatment, given the tumor conditions.

5. Conventional chemotherapy has a low effect on the prognosis of most tumors, but the availability of new targeted agents may improve the prognosis of some tumor formations.

Autor corespondent: Elena Țarcă E-mail: elatarca@gmail.com

CONFLICT OF INTEREST: none declared.

FINANCIAL SUPPORT: none declared.

This work is permanently accessible online free of charge and published under the CC-BY.