PMC8141844_01
Clinical features of patient at diagnosis. (A) Computerized Tomography scan of the abdomen and pelvis. (B) Fluorodeoxyglucose-positron emission tomography scan. (C) Hematoxylin and eosin stain, showing nests of pleomorphic epithelioid cells with occasional vacuoles and luminal structures.
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Australia) following 2 weeks of abdominal pain, vomiting, constipation, and rectal pain. A diffuse lower-abdominal mass was felt upon palpation, and computerized tomography (CT) revealed a large anterior multi-lobulated intraperitoneal mass abutting the abdominal wall and extending from above the umbilicus to the colovesical pouch inferiorly, with multiple enlarged mesenteric nodes in the upper abdomen ( Figure 1A ). The mass demonstrated high-grade FDG-PET activity ( Figure 1B ), including the right lobe of the liver, suggestive of metastatic disease. Some had large cytoplasmic vacuoles, and occasionally cells were arranged around a lumen ( Figure 1C ).
Strong, diffuse immunohistochemical staining of tumor cells. (A) CK AE1/AE3, (B) CK20, (C) Vimentin, (D) Loss of nuclear staining with INI1 and positive staining in the internal control stromal nuclei.
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INI1 staining in most cells ( Figures 2A-D ).
Sanger confirmation of missense mutations identified by whole exome sequencing analysis. (A) Heterozygous FANCM mutation (c.5857C>G, p.Gln1953Glu). (B) Heterozygous SMARCD2 mutation (c.311G>T, p.Arg104Leu). FP, forward primer; RP, reverse primer.
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Of these, two heterozygous missense mutations in the tumor-suppressor genes FANCM (c.5857C>G, p.Gln1953Glu) and SMARCD2 (c.311G>T, p.Arg104Leu) were confirmed by Sanger sequencing ( Figure 3 ).
Fluorodeoxyglucose-positron emission tomography scan response assessment during therapy. (A) Very good partial response prior to surgical resection. (B) At hepatic progression (metastatic lesions to segments 7 and 8 shown). (C) Complete remission prior to metronomic maintenance therapy.
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Repeat imaging showed a very good partial response ( Figure 4A ) and a further two cycles were administered prior to incomplete surgical resection of residual tumor, which included a pelvic mass attached to the bladder, an omental mass off the anterior abdominal mass, and small lymph nodes. FDG-PET scans revealed a continued partial response, with resolution of the pelvic tumor, but progression in the right (segments 7 and 8) and left (segment 3) lobes of the liver ( Figure 4B ). Chemotherapy was subsequently adjusted to ifosfamide (3 g/m2, Days 1 to 3) and doxorubicin (37.5 mg/m2, Days 1 and 2), repeated every 4 weeks. FDG-PET revealed a complete metabolic response following two cycles of therapy, and a further four cycles were administered, resulting in complete radiological remission ( Figure 4C ).