Download 5- Burg-Kurland CL, Purnell DM, Combs JW, Hillman EA, Harris CC

An Unexpected Reason of Elevated Human Chorionic
Gonadotropin
in
Young
Woman:
Cervical
Squamous
Carcinoma
Running Title:
Elevated Human Chorionic Gonadotropin with Cervical Squamous Carcinoma
Abstract: BHCG (human chorionic gonadotropin) has been used for decades to detect
pregnancy, trophoblastic tumors, as well as congenital defects. Surprisingly, it can be
elevated not only in trophoblastic disease, but also in squamous cell cancers.
A 33 -year- old Asian female had irregular menses accompanied with feelings of heaviness in
vagina. In addition to routine investigation, we measured serum BHCG (based on patient’s
complaint of amenorrhea), which was 50.05 ml UI/ml. Cervical biopsy revealed: Non
Keratinized Large cell Squamous Ca. After excluding other causes, BHCG elevation was
explained by the ectopic secretion of cancer cells line. A biopsy of the cervical tissue was
stained and BHCG production was positive. As a result, we should keep in mind the
possibility of ectopic secretion of BHCG from non trophoblastic disease.
Key words: Cervix, BHCG, Squamous cell carcinoma.
Introduction:
BHCG (human chorionic gonadotropin) has been used to detect pregnancy. Thus, it elevates
in case of normal pregnancies as well as ectopic pregnancies. In addition, it can be used to
diagnose and follow up trophoblastic tumors. Also BHCG hormone takes part in double and
triple test which screen fetal congenital abnormalities (1).
In this case, the patient has been diagnosed with cervical large SCC, and the peculiar finding
was abnormal elevation of serum BHCG. Furthermore, this elevation wasn't high enough to
be explained neither by pregnancy nor by trophoblastic tumors.
We describe a case with uterine cervical large squamous cell carcinoma with unexplained
elevated serum BHCG.
After ruling out pregnancy and trophoblastic disease, we suggest that this elevation can be
explained by ectopic secretion of BHCG from cancer cell line.
Case presentation:
A 33 -year- old Asian woman; gravida 6, parity 5, abortion 1, presented with feeling of
heaviness and pressure in pelvis that was progressing for the last two weeks which
accompanied with amenorrhea as well as progressing dysuria. Speculum transvaginal
examination revealed a fixed cervix. Palpation of the rectovaginal septum revealed a thick,
hard, irregular septum. In addition, during digital rectal examination, parametrial, uterosacral,
and pelvic sidewall involvement had been palpated.
Ultrasonography demonstrated 57mm*40mm cervical mass. Cervical biopsy has been
performed; grossly, cervical biopsy consisted of multiple fragments of white yellow, soft and
firm tissue, measuring 1.1*1*0.4cm for the largest fragment and 0.4*0.3*0.2 for the smallest
one. On routine pathologic examination, Hematoxilen Eosin (H&E) showed infiltrative nests
of neoplastic squamous cells with eosinophilic cytoplasm and prominent nucleolus and
lacked keratin pearls. Histopathologic findings were consistent with non-keratinizing
squamous cell carcinoma figure 1. Immunohistochemical stain showed cytoplasmic positivity
with BHCG figure 2.
Computed tomography (CT) scans of the abdomen and pelvis showed a heterogeneous mass
in the cervix that measures 5 cm, in addition, (3.5 *2) cm liver metastasis has been detected
figure 3-4.
An intravenous pyelogram (IVP) imagining illustrated bilateral dilated pelvicalyceal system
of kidneys with dilated tortuous right ureter figure 5.
Her β-human chorionic gonadotrophin level was found to be slightly elevated 50.05 mlU/ml.
In our case the patient was end stage disease. We referred the patient to the
radiochemotherapy unite.
As far as we know, this value is inexplicable neither by pregnancy nor by trophoblastic
tumors, so it can be attributed to the ectopic expressions of BHCG from squamous cancer cell
line.
Discussion:
Squamous cell tumors comprise 75 percent of all cervical cancers (2). Although screening
and early diagnosis have significantly reduced the incidence of and mortality from cervical
carcinoma, it is still a leading cause of death in developing countries. Human papilloma virus
infection has been postulated to be the primary cause of cervical cancer. The large cell non
keratinizing variety accounts for the majority of tumors and by definition they do not have
keratin pearls. The cells are arranged in nests and cords, have a moderate amount of
eosinophilic cytoplasm but the cell boundaries are not as distinct as keratinizing carcinomas.
Nevertheless, genetic alterations have also been implicated in cervical tumorigenesis that
include the activation of proto-oncogenes and deregulation of tumor suppressor gene.
HCG consists of a 92 amino acid alpha subunit and a 145 amino acid beta subunit,
which shares a mutual evolutionary sequences with transforming growth factor(TFG).
BHCG paves the way to the advanced cancer to invade and metastasize by inhibiting
apoptosis process in cancer cells and promotion of invasion proteases by cancer
cells.(3)
Several researches postulate the possibility of utilizing BHCG as a tumor marker in diagnose
and follow up SCC not only in the uterine cervix cancers (4), but also in SCC of esophagus
(5). Furthermore, adenocarcinoma of uterine can secretion BHCG (6).
We describe a patient that diagnosed with cervical SCC that accompanied with elevated
serum BHCG and positive tissue expression of BHCG, that mandate us to find out the
correlation between this ectopic production of BHCG from non trophoblastic cells.
According to Li D et al, hCG beta expression correlates with decreased tumor cell apoptosis
and may be takes part in tumor vascularization and dissemination (7). Furthermore, Hameed
et al (8) suggest that poorly differentiated squamous cell carcinoma of uterine cervix showing
immunoreactivity for beta-hCG should be distinguished from choriocarcinoma and other
trophoblastic tumors.
Elevated serum BHCG levels baldly suggests the correlation between its levels fluctuations
with aggressive behavior of cancer cell line.
Conclusion:
All in all, when we encounter a patient with slightly elevated serum BHCG, we have to keep
in mind the possibility of SCC as a resource of ectopic secretion. More advanced
researches are warranted to evaluate the treatment choices of invasive cancers that are
directed to pathogenisis of BHCG
References
1-Carl L Buckner,1 Lisa Wilson,2 and Christine N. P Gynecol Oncol, 2007 Jul 4;106(1):35-43. Epub 2007
May 4.
2-Berek JS, Howe C, Lagasse LD, et al: Pelvic exenteration for recurrent gynecologic malignancy:
survival and morbidity analysis of the 45-year experience at UCLA. Gynecol Oncol 99:153, 2005
3- Laurence A Cole, HCG variants, the growth factors which drive human malignancies, Am J Cancer Res
2012;2(1):22-35.
4- Kinugasa M, Nishimura R, Hasegawa K, Okamura M, Kimura A, Ohtsu F, Takeuchi K Assessment of
urinary beta-core fragment of hCG as a tumor marker of cervical cancer] Nihon Sanka Fujinka Gakkai
Zasshi. 1992 Feb;44(2):188-94
5- Burg-Kurland CL, Purnell DM, Combs JW, Hillman EA, Harris CC, Trump BF Immunocytochemical
evaluation of human esophageal neoplasms and preneoplastic lesions for beta-chorionic gonadotropin,
placental lactogen, alpha-fetoprotein, carcinoembryonic antigen, and nonspecific cross-reacting antigen.
Cancer Res. 1986 Jun;46(6):2936-43
6 -Collins RJ, Wong LC.-Adenocarcinoma of the uterine cervix with beta-hCG production: a case report
and review of the literature. Gynecol Oncol. 1989 Apr; 33(1):99-107
7- Li D1, Wen X, Ghali L, Al-Shalabi FM, Docherty SM, Purkis P, Iles RK -HCG beta expression by
cervical squamous carcinoma--in vivo histological association with tumour invasion and apoptosis.
Histopathology. 2008 Aug;53(2):147-55. doi: 10.1111/j.1365-2559.2008.03082.x.
8-Hameed A1, Miller DS, Muller CY, Coleman RL, Albores-Saavedra J Frequent expression of betahuman chorionic gonadotropin (beta-hCG) in squamous cell carcinoma of the cervix Int J Gynecol
Pathol. 1999 Oct;18(4):381-6.
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Figure (1)- Atypical infiltrative squamous islands in the fibrohyalinized cervical stroma,
H&Ex200.
Figure (2)- Cytoplasmic positivity with hCG in squamous cell carcinoma, X400.
Figure 3-4 a heterogeneous mass in the cervix that measures 5 cm, in addition, (3.5 *2) cm
liver metastasis has been detected.
Figure 5 Bilateral dilated pelvicalyceal system of kidneys with dilated tortuous right ureter
Figure 3-4 a heterogeneous mass in the cervix that measures 5 cm, in addition, (3.5 *2) cm
liver metastasis has been detected.
Figure 5 Bilateral dilated pelvicalyceal system of kidneys with dilated tortuous right ureter