Bankstown Hospital - Grand Rounds - Further Reading

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Beware the beta

Abdelwahab, H., et al. (2021). "S3107 A Rare Case of Metastatic AFP and Beta HCG-Producing Gastric Carcinoma." Official journal of the American College of Gastroenterology | ACG 116: S1283  https://journals.lww.com/ajg/fulltext/2021/10001/s3107_a_rare_case_of_metastatic_afp_and_beta.3111.aspx PDF AT LINK

Alpha fetoprotein (AFP) is an oncogenic glycoprotein which is normally expressed during gestation. AFP can be secreted during the prenatal period by yolk sac, fetal liver, and some gastrointestinal cells. AFP is used as a biomarker for yolk sac tumor, tumors of gonadal origin, hepatocellular carcinoma (HCC), and certain gastric carcinomas (GCs). Extrahepatic AFP-producing carcinomas are relatively rare. 1.3-15% of GC is classified as AFP-producing GC (AFPPGC). AFPPGC is an aggressive, usually advanced tumor with higher incidence of metastasis and poor prognosis. We present a case of metastatic AFPPGC which initially was thought to be a metastatic pancreatic adenocarcinoma based on imaging.

Case Description/Methods:

A 54-year-old otherwise healthy male presented with three weeks of dry, persistent cough associated with diffuse abdominal pain and distension, decreased oral intake and unintentional weight loss. Beside generalized abdominal distension and tenderness, the physical exam was unremarkable. Laboratory studies revealed elevated LFTs, AFP of 16916 ng/mL (reference range 10-20 ng/mL) and beta HCG of 2399 mIU/mL (reference range < 2 mIU/mL). Testicular ultrasound was unremarkable. CT scan of abdomen and pelvis and subsequent MRCP showed innumerable masses in the liver, extensive upper abdominal lymphadenopathy, and a large mass arising from the head of the pancreas, likely representing primary pancreatic tumor. He underwent endoscopic ultrasound (EUS) which revealed a large gastric ulcer and numerous malignantappearing peripancreatic lymph node (LN), but no pancreatic mass was seen. LN and gastric ulcer biopsy confirmed AFPPGC [Figure 1]. Patient’s clinical condition deteriorated quickly, and he opted for non-aggressive treatment. Eventually, he was discharged to inpatient hospice and died within one month.

Discussion:

AFPPGC is one of the most aggressive gastric tumors due to its high incidence of early liver and LN metastasis with poor prognosis compared with other GCs. The poor prognosis is attributed to the AFP effect as a growth promoter. Our patient not only had elevated AFP but also had elevated beta HCG which is extremely rare. Tissue biopsy with immunohistochemical staining is helpful in arriving at the diagnosis and differentiating it from metastatic HCC. Although there is no current standardized treatment for AFPPGC, surgical resection and chemotherapy have been reported. Clinicians should be aware of this rare tumor due to its rapid progression and early metastasis

Fujimoto, S., et al. (1987). "The presence of an aberrant type of human chorionic gonadotropin in patients with gastric or colorectal cancer." The Japanese journal of surgery 17(5): 382-387  https://doi.org/10.1007/BF02470638  REQUEST ARTICLE

Beta subunits of human chorionic gonadotropin (β-hCG) and human chorionic gonadotropin-like substance (hCGLS) were measured radioimmunologically in the serum and malignant tissue from patients with gastrointestinal cancer. Since serum β-hCG and hCGLS correlate closely to those in cancer tissues, it is assumed that these two gonadotropins originate from cancer tissues. The serum hCGLS levels in 54 patients with gastrointestinal cancer were significantly higher, when compared with the findings in 19 healthy volunteers and 10 peptic ulcer patients. The frequency of high levels of serum hCGLS accounted for 71 per cent of those with operable gastric cancer, 44 per cent of those with inoperable gastric cancer, 100 per cent of those with operable colorectal cancer, and 67 per cent of those with inoperable colorectal cancer. On the contrary, serum β-hCG levels did not differ between the volunteers and the cancer patients. In the 17 sera and 15 cancer tissues assayed, β-hCG did not correlate to hCGLS. Moreover, the high levels of β-hCG in cancer patients occurred in only 1/14 (7.1 per cent) of the assayed serum, and in 5/14 (35.7 per cent) of the cancer tissue. The increased production of these two hCGs may result from neoplastic trans-fromation of an unrestrained fetal genome responsible for hCG production during gestation. It is assumed that the increased producibility of a defective hCG, i.e., an aberrant hCG such as hCGLS, is characteristic of malignant tumors.

Kang, S., et al. (2019). "A case report of paraneoplastic syndrome in β-hCG-secreting duodenal adenocarcinoma." J Gastrointest Oncol 10(6): 1151-1156   2219-679x https://pmc.ncbi.nlm.nih.gov/articles/PMC6954993/ REQUEST ARTICLE

Human chorionic gonadotropin (hCG) is a glycoprotein hormone that is used in clinical practice to detect pregnancy and serves as a sensitive marker for trophoblastic tumors. Other organs besides placental trophoblasts naturally express the hormone at low levels, which can be elevated in nontrophoblastic malignancies. Some studies have suggested that elevated β-hCG levels in nontrophoblastic tumors are a sign of aggressive disease and strongly associated with poor prognosis. We describe a case of a 50-year-old post-menopausal woman with metastatic duodenal adenocarcinoma who presented with a negative pregnancy test that later changed to positive. Biopsy of the primary duodenal mass showed positive immunohistochemical expression of β-hCG. The patient was also found to have multiple brain metastases, which is uncommon in gastrointestinal cancer. This is a rare case of paraneoplastic syndrome in a β-hCG-secreting duodenal adenocarcinoma.

Shinde, S. R., et al. (2009). "Ectopic Human Placental Lactogen and β-Human Chorionic Gonadotropin in Gastric Fluid of Patients with Malignant and Non-Malignant Conditions of the Stomach." Oncology 38(5): 277-280  https://doi.org/10.1159/000225570 REQUEST ARTICLE

Human placental lactogen (hPL) and β-human chorionic gonadotropin (β-hCG) in gastric aspirates and sera of 24 patients with malignant (12 patients) and non-malignant (12 patients) conditions of the stomach were studied. In patients with cancer of the stomach, hPL and β- hCGwere found to be present in gastric aspirate at higher frequency than in serum. The concentration of these hormones in gastric aspirate was higher than in serum. In 2 patients with duodenal ulcer β- hCGwas found to be present in gastric aspirate, 1 of them having the hormone in circulation as well, while none of the 12 patients with non-malignant conditions of the stomach showed presence of hPL in their gastric aspirate or serum.

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BJOG: An International Journal of Obstetrics & Gynaecology publishes original, peer-reviewed research in all areas of obstetrics and gynaecology. Its content is enriched with expert commentaries, journal club, CPD/CME, perspectives articles, and digital content such as audio podcasts and video abstracts.

Obstetrics & Gynecology 01/1995 - Current