Case Report: First-Line Immune Checkpoint Inhibitor Plus Chemotherapy for Oral Metastasis in a Patient with Ultra High-Risk Gestational Choriocarcinoma

Figures & data

Figure 1 CC pathology and ¹⁸F-FDG PET/CT images. (A and B) Clinical responses of the patient to DC+ICI treatment: PR. (C) HE-stained section of the tumor showed extensive hemorrhage and necrosis at low magnification, the biphasic feature of mixed cytotrophoblasts (black triangle) and syncytiotrophoblasts (black arrow) and nuclear division in tumor cells (star) at high magnification. In some regions, tumors are mainly composed of mononuclear cytotrophoblasts, and syncytiotrophoblasts are few and inconspicuous, which is easy to be misdiagnosed as poor-differentiated carcinoma. Immunohistochemical markers provided further support for the diagnosis of CC.

Abbreviations: CC, choriocarcinoma; ¹⁸F-FDG PET/CT, 18-fluorine-fluorodeoxyglucose positron-emission-tomography/computed tomography; DC, docetaxel and cisplatin; ICI, immune checkpoint inhibitor; PR, partial response; HE, hematoxylin-and-eosin; 3D, three dimensional; CK, cytokeratin; HCG, human chorionic gonadotropin.

Figure 2 Tumor microenvironment of this patient. (A) Targeted next-generation sequencing analysis (483-gene panel) showed high tumor mutation burden (33.571 muts/MB). (B) Multiplex immunofluorescence staining results.

Figure 3 DNA polymorphic analysis. (A–D) Genetic profiles of 21 highly polymorphic short tandem repeats (STRs) from tumor, the patient and spouse were compared. At 7/21 valid loci (D19S433, D7S820, D8S1179, TPOX, Penta E, D12S391, FGA) examined, tumor sample was found to contained both the maternal and paternal allele, demonstrating its gestational origin. Y-axis: fluorescence intensity of the labeled product. X-axis: allelic sizes in base pairs, such that the number stands for repeat size in each short tandem repeat locus and can be highly variable among individuals.

Figure 4 Clinical course. The patient underwent gingival resection, relapse, and was transferred to our hospital to receive 2 cycles of DC+ICI treatment, followed by 3 cycles of FEVA chemotherapy. Pathologic images revealed the biphasic growth pattern of cytotrophoblasts (yellow triangle) and syncytiotrophoblasts (yellow arrow). Dynamic observation of lesions imaging (red arrow) and β-HCG levels were shown below.

Abbreviations: DC, docetaxel and cisplatin; ICI, immune checkpoint inhibitor; FEVA, 5-fluorouracil, actinomycin D, vincristine and etoposide; β-HCG, β-human chorionic gonadotropin; HE, hematoxylin-and-eosin; PD-L1, programmed cell death ligand-1; CPS, combined positive score; NGS, next-generation sequencing; PR, partial response; MOF, multiple organ failure.

Table 1 Cases of Oral Metastasis by Choriocarcinoma with Survival Data in Reviewed Literatures

Case No.	Source	Gender	Age	Oral Neoplasm at First Sign	Lesion Location on Oral Cavity	Metastases Besides Oral Cavity	Major Lesion Manifestation	NGC or GCC	Was It Surgically Exercised	Chemotherapy Regimen	Prognosis
1	Sato, 1978^Citation23	Female	32	Yes	Gingiva	Lung	Gingival bleeding	GCC	No	Methorexate	Death
2	Altintas, 1995^Citation4	Female	26	Yes	Gingiva	No	Pain	GCC	No	Methotrexate, actinomycin D and cyclophosphamide	CR for 2 years
3	Kösem, 2004^Citation2	Female	37	Yes	Gingiva	ND	Nausea, vomit and gingival bleeding	GCC	No	ND	ND
4	Bakeen, 1976^Citation3	Female	25	No	Gingiva	Lung, pelvis	Vagina and gingival bleeding	GCC	No	Methotrexate, chlorambucil and actinomycin	Death
5	Shafiee, 2011^Citation5	Female	23	No	Gingiva	Lungs, liver, brain	Vomit, poor appetite	GCC	No	No	Death
6	Tsuge, 1962^Citation17	ND	ND	ND	Gingiva	ND	ND	ND	ND	ND	ND
7	Roa, 1972^Citation18	ND	ND	ND	Gingiva	ND	ND	NGC	ND	ND	ND
8	Mori, 1974^Citation19	Female	47	Yes	Gingiva	Lung, brain	Swelling, Bleeding	NGC	Yes	ND	Death
9	Nespeca, 1980^Citation20	Male	77	Yes	Gingiva	Brain, neck, lungs, kidney	Gingival bleeding	NGC	No	ND	Death
10	Scolozzi, 2006^Citation8	Male	36	Yes	Gingiva	Duodenum, brain, lung	Dyspnea	NGC	No	Platinol and Etoposide, followed by Platinol, Etoposide, and Ifosfamide	Death
11	Bhatia, 2007^Citation21	Male	22	Yes	Gingiva	Skin	Gingival and skin lesions	NGC	ND	ND	ND
12	Khanfir, 2011^Citation6	Female	26	Yes	Gingiva	Lung, renal	Bleeding	NGC	No	Actinomycin, cisplatin and etoposid	CR for 4 years
13	Velasco, 2013^Citation7	Male	33	Yes	Gingiva	Brain, neck, lungs, liver, retroperitoneum	Dysphagia, weight loss	NGC	No	Cisplatin, etoposide, bleomycin for 2 cycles, then placitaxel, cisplatin ifosfamide for 3 cycles	Death

Note: The reference numbers are listed on the top left corner of the “Source” column.

Abbreviations: ND, not describe; GCC, gestational choriocarcinoma; NGC, non-gestational choriocarcinoma; CR, complete response.

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