Diagnosing low-grade central osteosarcoma using a neural network mathematical model: a case report and review

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Abstract

BACKGROUND: Diagnosing low-grade central osteosarcoma is associated with a significant challenge because, according to radiological and histological findings, the condition closely resembles various benign lesions, most commonly being misdiagnosed as fibrous dysplasia. Convolutional neural network-based mathematical models have been successfully applied for the automated analysis of digital histopathological images, including tumor classification, regions of interest segmentation, and identification of morphological features of malignancy.

CASE DESCRIPTION: This paper presents a clinical case of a 33-year-old female patient in whom, following a pathologic fracture of the femoral diaphysis, the lesion was long misinterpreted as fibrous dysplasia. Upon re-evaluation of histological slides and repeat biopsy at the N.N. Priorov National Medical Research Center of Traumatology and Orthopedics, the diagnosis of low-grade central osteosarcoma with areas of dedifferentiation and formation of high-grade osteosarcoma foci was established. For additional diagnostic confirmation, a convolutional neural network (ResNet-101)-based mathematical model previously developed by the authors for automated detection of pathologic mitoses on digital histopathological images was applied. The model analyzed scanned slides (Leica Aperio CS2, ×400), identifying several structures with a high probability of pathologic mitoses (maximum confidence scores: 99% and 92%), consistent with the conclusions of two experienced pathologists, thereby confirming the malignant nature of the lesion.

CONCLUSION: This paper presents a clinicopathological and radiologic description of the condition, discusses diagnostic challenges and similarities with fibrous dysplasia and other benign lesions, and evaluates the potential and limitations of artificial intelligence techniques in pathology for rare low-mitotic tumors. Emphasis is placed on the role of neural network analysis as an auxiliary tool for improving reproducibility and sensitivity of mitosis detection, the need for multicenter model validation, and the implementation of stain normalization and interpretability of results for clinical application.

About the authors

Gennadiy N. Berchenko

Priorov National Medical Research Center of Traumatology and Orthopedics

Author for correspondence.
Email: berchenko@cito-bone.ru
ORCID iD: 0000-0002-7920-0552
SPIN-code: 3367-2493

MD, Dr. Sci. (Medicine), Professor

Russian Federation, Moscow

Alexander K. Morozov

Priorov National Medical Research Center of Traumatology and Orthopedics

Email: ak_morozov@mail.ru
ORCID iD: 0000-0002-9198-7917
SPIN-code: 4447-8306

MD, Dr. Sci. (Medicine), Professor

Russian Federation, Moscow

Vadim Y. Karpenko

Priorov National Medical Research Center of Traumatology and Orthopedics

Email: Doctor-kv@cito-priorov.ru
ORCID iD: 0000-0002-8280-8163
SPIN-code: 1360-8298

MD, Dr. Sci. (Medicine)

Russian Federation, Moscow

Olga B. Shugaeva

Priorov National Medical Research Center of Traumatology and Orthopedics

Email: Olga.Shugaeva2013@yandex.ru
ORCID iD: 0000-0002-0778-5109
Russian Federation, Moscow

Alexander F. Kolondaev

Priorov National Medical Research Center of Traumatology and Orthopedics

Email: klndff@inbox.ru
ORCID iD: 0000-0002-4216-8800
SPIN-code: 5388-2606

MD, Cand. Sci. (Medicine)

Russian Federation, Moscow

Nina V. Fedosova

Priorov National Medical Research Center of Traumatology and Orthopedics

Email: hard_sign@mail.ru
ORCID iD: 0000-0002-0829-9188
SPIN-code: 5380-3194
Russian Federation, Moscow

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Supplementary files

Supplementary Files
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1. JATS XML
2. Fig. 1. X-ray of the femur after osteosynthesis for a pathologic fracture. A healed pathologic fracture of the left femoral diaphysis is visualized; bone structure is altered, with focal areas of rarefaction and coarse trabecular remodeling.

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3. Fig. 2. Changes in femoral bone structure 5 years later. Multislice computed tomography in the axial plane (a) and in the sagittal plane obtained by reconstruction (b) demonstrates an enlarged lytic destruction focus with cortical layer disruption along the anterolateral surface, a massive soft-tissue tumor component with indistinct margins, and signs of infiltrative growth.

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4. Fig. 3. a, among fibroblast-like cells with mild nuclear atypia, a pathologic mitosis is seen (arrow); hematoxylin-eosin stain, ×1000 b, area of atypical osteogenesis (asterisks); hematoxylin-eosin stain, ×100.

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5. Fig. 4. a, bundles of fibroblast- and osteoblast-like cells arranged in various directions, with marked atypia (asterisks) and pathologic mitosis (arrows); hematoxylin-eosin stain, ×200; b, formation of a layer of atypical osteoid lacking clear signs of calcification (asterisks); hematoxylin-eosin stain, ×100.

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6. Fig. 5. a, the model identified a “pathologic mitosis” object with a probability of 99%; hematoxylin-eosin stain, ×400 b, the model identified a “pathologic mitosis” object with a probability of 92%; hematoxylin-eosin stain, ×400.

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