PMC7166265_01
Morphologic features and immunophenotype of SCLC from supraclavicular lymph node biopsy obtained at the time of diagnosis in 2009. (a) H&E stain displaying the characteristic morphologic features of small-cell carcinoma including high nuclear to cytoplasm ratio, hyperchromatic nuclei with salt and pepper chromatin, inconspicuous nucleoli, and frequent mitoses. (b) AE1/AE3 stain demonstrating focal punctate or discontinuous staining that is usually observed in SCLC. (c, d) The neoplasm is diffusely positive for neuroendocrine markers synaptophysin and chromogranin. (e) TTF-1 expression is positive, suggesting pulmonary origin of tumor. (f) PD-L1 immunostain was negative in the initial biopsy and subsequent biopsied metastatic sites.
CRIONM2020-8026849.001.jpg
PMC7166265_01_CRIONM2020-8026849.001.jpg
fig1
Histopathology (Figure 1) showed the morphologic features of SCLC including small to medium size cells, high nuclear/cytoplasmic ratio, salt and pepper chromatin with inconspicuous nucleoli, nuclear molding, and high mitotic activity.
Patient's disease course timeline. Black arrow: Surgical resection of intramedullary metastasis at C6-7; Red arrow: stereotactic radiosurgery to 6, 9, and 11 brain lesions; SCLC: small-cell lung cancer; CR: complete response; PR: partial response; SD: stable disease; PD: progressive disease; EP: etoposide/platinum; T: topotecan; PCI: prophylactic cranial irradiation; E: etoposide; Ev: everolimus; Tem: temozolamide; D: docetaxel; Su: sunitinib; LAD: lymphadenopathy; XRT: external beam radiation therapy.
CRIONM2020-8026849.002.jpg
PMC7166265_01_CRIONM2020-8026849.002.jpg
fig2
Thus, he was deemed to have limited stage disease and was treated accordingly with cisplatin and etoposide and concurrent radiation therapy (Figure 2).
Top:CT and PET-CT images April 2012 before alisertib showing 2.1 cm R hilar mass (a) with SUV 4.8 (b) and R para-tracheal soft tissue prominence with fibrotic changes in previously irradiated field (c) with SUV 5.2 (d). Bottom:CT and PET-CT images December 2012 after 10 cycles of alisertib showing resolution of R hilar mass (a, b) and unchanged R para-tracheal cicatricial changes (c) with maximum SUV of 2.3 (d).
CRIONM2020-8026849.003.jpg
PMC7166265_01_CRIONM2020-8026849.003.jpg
fig3
He experienced an objective response after 4 cycles and near complete response after 10 cycles of therapy (Figure 3).
Top:PET-CT chest, abdomen, and pelvis before initiation of nivolumab (July 2015) showing R para-tracheal soft tissue thickening and 3.2 cm L para-tracheal lymph node (a), 2.6 cm R hepatic dome lesion (b), 3.8 cm R adrenal and 4.1 cm L adrenal nodules (c), and multiple pancreatic lesions in the head, body, and tail (c, d). In addition (not shown), the patient had other metastases involving bones, mediastinal and retroperitoneal lymph nodes, and pleural and peritoneal surfaces. The maximum SUV values for R-para-tracheal thickening, L para-tracheal lymph node, hepatic lesion, R adrenal nodule, L adrenal nodule, and pancreatic lesions were 5.2, 6.83, 13.08, 11.9, 9.9, and 11.4, respectively. Bottom:PET-CT chest, abdomen, and pelvis after 16 weeks of nivolumab (December 2015) showing resolution of L para-tracheal lymphadenopathy (a), decrease in R hepatic dome lesion to 1.2 cm (b), decrease in L adrenal nodule to 1.4 cm (c), and resolution of R adrenal (d), and all pancreatic lesions (c, d). Other metastatic lesions (not shown) in the bone, mediastinal and retroperitoneal lymph nodes, and pleural and peritoneal surfaces have completely resolved. The maximum SUV for R hepatic dome lesion has reduced from 13.08 to 2.0, and no increased metabolic activity was detected in the L adrenal nodule. Other than equivocal increased metabolic activity in previously irradiated R para-tracheal region (SUV 2.4), there was no increase in metabolic activity anywhere else.
CRIONM2020-8026849.004.jpg
PMC7166265_01_CRIONM2020-8026849.004.jpg
fig4
He had evidence of partial response at 8 weeks of therapy and near complete response at 16 weeks of therapy in December 2015 (Figure 4).