case_images: PMC10646488_01
case_images: (A) CT enhancement scan shows a primary tumor in the left hilum with mediastinal and left hilar lymph node metastasis; (B) primary lung lesions were reduced significantly after two months; (C) CT scan demonstrating a dramatic shrinkage of the primary tumor after taking alectinib for 21 months; (D) HE staining at 100x magnification; (D) (a-d) Immunohistochemical stain revealed that CD56 (+), Syn (+), TTF-1 (+), and Ki-67 (+) (80%), x100; (E) ECT showed the 6th thoracic vertebra and left localized iliac metastases; (F) distinctly decreased uptake of 99mTc-MDP in bone metastases after taking alectinib for 18 months.
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case_images: PMC10646488_01_fonc-13-1227980-g001.jpg
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case_images: Chest Hospital with a 7-month history of "interrupted cough and wheezing." Laboratory tests revealed abnormally elevated levels of neuron-specific enolase (NSE) (23.79 ng/ml; normal range 5.00-15 ng/ml). Contrast-enhanced chest CT showed a tumor in the left hilum ( Figure 1A ) with mediastinal and left hilar lymph node metastasis. A CT-guided lung biopsy was performed, along with baseline whole-body tumor burden and bone scanning ( Figure 1E ). TTF-1, and a Ki-67 index of 80% [ Figure 1D  (a-d)]. The patient was considered to have advanced NECLC with multiple bone metastases, cT3N2M1c, and Union for International Cancer Control (UICC) After two months of treatment with alectinib, the primary lung lesions responded significantly to treatment ( Figure 1B ), and the subsequent CT scan showed a durable response in the primary tumor. Additionally, there was a dramatic reduction in 99mTc-MDP uptake in bone lesions 18 months later ( Figure 1F ). The patient receives alectinib without evidence of disease progression with PFS for 21 months ( Figure 1C ).
case_images: PMC10646488_02
case_images: (A) Primary tumor in the right upper lung field; (B) Primary lung lesions distinctly shrink in 2 months; (C) Primary tumor showed a further decrease and almost disappeared after taking alectinib for 32 months; (D) positive ALK protein expression by IHC staining using the anti-ALK antibody (clone D5F3) characterized by intense, diffuse cytoplasmic staining; (D) (a-e) a, HE staining at 100x magnification; (b-e) Immunohistochemical stain revealed that CD56 (+), Syn (+), TTF-1 (+), and Ki-67 (+) (90%), x100; (E) ultrasonography (USG) of bilateral superficial cervical lymph nodes metastasis; (F) USG of bilateral superficial cervical lymph nodes shrank obviously after 20 months of therapy.
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case_images: Cancer Hospital with a palpable mass in the right supraclavicular fossae. Chest CT revealed a 4 cm irregularly shaped solitary tumor in the right upper lung field ( Figure 2A ). Ultrasonography (USG) of the superficial cervical lymph nodes (LNs) detected supraclavicular lymph node metastasis ( Figure 2E ) but no thyroid gland lesion. The Ki-67 index was 90% [ Figure 2D  (a-e)]. HE staining under the microscope revealed distinct neuroendocrine differentiation, characterized by non-small cell morphology, abundant cytoplasm, and well-defined nucleoli [ Figure 2D  (a)]. Given the patient's never-smoker status, a molecular work-up for potentially actionable mutations was conducted using Ventana ALK IHC (D5F3), which unexpectedly revealed positive staining for ALK ( Figure 2D ), which was confirmed by NGS, revealing an EML4-ALK rearrangement (E20:A20). The patient immediately started on second-generation ALK inhibitor alectinib at 600 mg b.i.d. in October 2020. The patient showed a rapid excellent tumor response to alectinib, with shrinkage of the pulmonary nodule in 2 months ( Figure 2B ). Despite the reduced alectinib dose, the patient continued demonstrating sustained clinical, radiographic, and biochemical responses while on alectinib for 32 months at writing, without any other drug-related toxicities ( Figures 2C, F ).