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Fig 1.

Morphological and histological characterization of tumors from patient #1, presenting concomitant NB and ACT.

A) Schematic representation based on patient #1 image files demonstrating adrenocortical tumor in right adrenal gland and the neuroblastoma in left paravertebral region. B) Right adrenocortical tumor from patient #1 measuring 2,0 x 1,8 x 0,8 cm. The microscopic examination revealed in I) cortical region of non-tumoral adrenal; II) medullary region of non-tumoral adrenal; III) adrenocortical tumor characterized by atypical large pleomorphic cells with acidophilic cytoplasm, presenting Fuhrman nuclear atypia grade 3 (H&E 100x magnification). C) Histological examination of left paravertebral tumor from patient #1. The neuroblastoma presented dimensions of 4,3 x 3,2 x 1,5 cm and was characterized by small round primitive cell clusters (H&E staining, 40x magnification). In detail, neuroblasts at different maturation stages embedded in neurofibrillary stroma (H&E, 400x magnification).

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Fig 2.

Morphological and histological characterization of tumors from patient #2, presenting concomitant NB and ACT.

A) Schematic representation based on patient #2 macroscopic findings shows the right adrenal gland presenting concomitant occurrence of adrenocortical adenoma and in situ neuroblastoma. B) The macroscopic examination of tumor demonstrates a solid and well-circumscribed adrenocortical tumor, completely surrounded by a thin fibrous capsule (arrow). The cut surface shows a yellowish, shiny, and homogeneous neoplasm with slightly lobular architecture. C) The left half of the picture shows the adrenocortical tumor surrounded by a thin and fibrous capsule (HE, 100x). Insert a detail demonstrating tumor cells of large size, with huge and eosinophilic cytoplasm, large nuclei, with central and conspicuous nucleoli. (HE, 400x). D) In situ neuroblastoma can be identified as a slightly pale region indicated by an arrow. E) Microscopic analysis from the pale region of remainder adrenal gland shows well-preserved cortical parenchyma cells (arrowheads). The inner medullary zone is heavily infiltrated by in situ neuroblastoma (arrows) (HE, 40x). Insert, a detail showing tumor composed of small round blue cells with scant cytoplasm, and dark, hyperchromatic nuclei with frequent formation of Homer-Wright rosettes (thin arrows) (HE, 100x).

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Table 1.

Characteristics of p.R337H positive patients.

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Fig 3.

Immunohistochemical p53 staining on p.R337H positive NB tumors.

A, B) Representative images of nuclear p53 accumulation on neuroblastoma cells from patients 3 and 7, respectively (100x magnification).

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Table 2.

Clinico-biological data of neuroblastoma patients according to p.R337H status.

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Table 3.

Cancer family history of the 83 neuroblastoma patients according to p.R337H status.

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Table 4.

Literature review on TP53 polymorphisms in neuroblastoma.

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Table 5.

Literature review on TP53 mutations in association with neuroblastoma.

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