PMC8239351_01
CT scan 3d-reconstruction of the baseline tumor lesions (A) coronal plane; (B) sagittal plane). L1Vol1 = left thigh mass; L2Vol1 = lesion of the left dorsal muscles next to D11 vertebral body; L3Vol1 = lesion of the left dorsal muscles next to L5 vertebral body; L4Vol1 = lesion of the left gluteus muscles; L5Vol1 = lesion of the left iliopsoas.
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TB CT scan of March 2019 showed the left thigh mass of 170 x 135 mm, a similar mass in the context of the left iliopsoas (40 x 25 mm) and gluteus muscles (19 x 21 mm), other two tumoral nodules in the dorsal muscles next to D11 vertebral body (37 x 30 mm) and L5 vertebral body (40 x 30 mm) ( Figures 2A, B  and  3A ). The reactive inguinal lymphadenopathies were not viewable.
CT scan imaging of the tumoral lesions during patient's treatment history. Evolution during treatment of the tumoral lesions: lesions of the left dorsal muscles next to D11 vertebral body (arrow) and L5 vertebral body (arrowhead), lesion of the left gluteus (circle) and left thigh mass (asterisk). (A) before chemotherapy (March 2019), (B) after second cycle of chemotherapy and before crizotinib (May 2019), (C) after 4 months of crizotinib (September 2019), (D) after 7 months of crizotinib (December 2019).
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TB CT scan of March 2019 showed the left thigh mass of 170 x 135 mm, a similar mass in the context of the left iliopsoas (40 x 25 mm) and gluteus muscles (19 x 21 mm), other two tumoral nodules in the dorsal muscles next to D11 vertebral body (37 x 30 mm) and L5 vertebral body (40 x 30 mm) ( Figures 2A, B  and  3A ). The reactive inguinal lymphadenopathies were not viewable. According to the absence of clinical and radiological response to chemotherapy ( Figures 3B  and  4B ), the presence of this rare targetable mutation and the patient's preference to stop chemotherapy, the patient started crizotinib (250 mg orally, twice daily) as off-label therapy in May 2019. The CT scan of September 2019, also, showed a significant dimensional decrease of the left thigh mass (40 x 30 mm) and a complete regression of the lesions of the iliopsoas, gluteus and dorsal muscles ( Figure 3C ). In December 2019, after 7 months of therapy, an additional minimal shrinkage of the tumor mass was observed (38 x 30 mm) ( Figure 3D ).
Clinical presentation of the left thigh mass during patient's treatment history. (A) before chemotherapy (March 2019), (B) after second cycle of chemotherapy and before crizotinib (April 2019), (C) after 7 days of crizotinib, (D) after 3 months of therapy (August 2019), (E) after 7 months of therapy (December 2019).
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In the same month, in consideration of the rapid progression of the primary lesion ( Figure 4A ) and the final diagnosis of sarcoma, the start of standard chemotherapy with doxorubicin and ifosfamide was indicated. According to the absence of clinical and radiological response to chemotherapy ( Figures 3B  and  4B ), the presence of this rare targetable mutation and the patient's preference to stop chemotherapy, the patient started crizotinib (250 mg orally, twice daily) as off-label therapy in May 2019. After only 7 days of treatment, we observed a significant dimensional decrease of the left thigh mass ( Figure 4C ). In August 2019, after 3 months of therapy, an outstanding clinical response was observed ( Figure 4D ). In January 2020, after 8 months of treatment, in consideration of the outstanding clinical and radiological response and the patient's preference to remove all the visible disease, the patient underwent wide excision of the residual tight lesion ( Figure 4E ).
IHC analysis of the resected tumor. (A) Hematoxylin and eosin (H&E) stain, original magnification 10x: necrotic area (asterisk) and sclerotic tissue with residual neoplastic spindle cells. (B, C) H&E stain, original magnification 20x: foamy histiocytes (circle) and a vascularized fibrotic area of connective tissue (arrowhead) mark the tumor bed. (D) H&E stain, original magnification 40x: atypical spindled neoplastic cells set in a loose collagenous matrix with a mild inflammatory infiltrate. Neoplastic cells show hyperchromatic and enlarged nuclei (arrows).
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The neoplastic foci displayed spindle-shaped cells embedding in a loose myxoid stroma ( Figures 5A-D ) (TNM: ypT1, according to UICC:VIII ed. 2017).
Complete regression of multifocal local recurrence in the left thigh. (A) Post-contrast MR T1 fat saturated axial image of upper left thigh shows some irregular enhancing nodules in the anterior compartment (asterisk). (B) The same sequence obtained three months later in the same area reveals complete nodules disappearance.
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TB CT scan and the subsequent MRI ( Figure 6A ) showed a multifocal local recurrence in the left thigh without evidence of new distant metastasis. Therefore, in August 2020 we decided, in agreement with the patient, to resume the treatment with crizotinib. After 3 months of therapy (November 2020) the TB CT scan and the MRI ( Figure 6B ) showed a complete regression of the disease.