Case 225 - Discussion

Uploaded: 2008-05-15, Updated: 2008-05-18

 

 

HYDATIDIFORM MOLE

  • 1 /1000 pregnancies in US,  10 /1000 in Indonesia;

  • Risk is higher in pregnant women in their teens or between the ages of 40 and 50 years;

  • Essential histologic hallmark: edematous villi and trophoblastic hyperplasia;

  • Complete Hydatidiform Mole: Grossly, voluminous, gross hydropic changes; histology, markedly edematous villi with cistern formation and extensive concentric villous and extravillous trophoblastic hyperplasia; Villous blood vessels are generally lacking; Fetal tissues are absent.

  • Partial Hydatidiform Mole: histology: dilated hydropic villi (34 mm) with central cistern formation are present in a background of small, sclerotic, and normal-sized villi. The hydropic villi have indented or scalloped outlines with trophoblastic inclusions. Villous surfaces may have many tiny projections of syncytiotrophoblast forming notches. The trophoblastic proliferation is minimal and limited to the syncitiotrophoblast. Nuclear atypia is infrequent. Villous stromal blood vessels containing nuclear red blood cells and/or fetal tissues may be present.

  • A strongly paternally imprinted gene, the cell cycle inhibitor, p57, may be used to identify complete moles by absence of expression in the syncytial trophoblast and stromal cells of molar villi. Because p57 is paternally imprinted, and both the X chromosomes in complete moles are derived from the father, there is no expression of p57 protein.

  • Clinical Course: In complete moles, quantitative analysis of HCG shows levels of hormone greatly exceeding those produced by a normal pregnancy of similar age. The vast majority of moles are removed by thorough curettage. Virtually no partial and only 2.5% of complete moles evolve into choriocarcinoma. 10% complete moles develop into invasive moles. Because unattended complete moles may persist and recur, distinction of these moles from non-molar hydropic and partial molar gestations is important.

Feature

Complete Mole

Partial Mole

Karyotype

  • Diandric paternal-only, 46,XX or 46, XY;

  • Homozygous 46, XX: 90%, one sperm + an empty egg with duplication;

  • Heterozygous 46, XX or XY: 10%, two sperms + an empty egg.

  • Triploid in 99%, diandric monogynic;

  • Heterozygous: 90%, two heterozygous sperms + one normal egg;

  • Homozygous: 10%, one normal egg + one sperm with duplication.

Villous edema

All villi

Some villi

Trophoblast proliferation

Diffuse; circumferential

Focal; slight

Atypia

Often present

Absent

Fetal tissue Absent May present

Serum HCG

Elevated

Less elevated

HCG in tissue

++++

+

p57 Absent Expression

Behavior

2.5% choriocarcinoma, 10% invasive mole

Rare choriocarcinoma

INVASIVE HYDATIDIFORM MOLE

  • Definition: penetration and even perforation of the uterine wall by a mole, mostly complete mole;

  • Clinical presentation: vaginal bleeding and irregular uterine enlargement. Always associated with a persistent elevated HCG level and varying degrees of luteinization of the ovaries;

  • Histology:  

    • The diagnosis of an invasive mole can only be made on a hysterectomy specimen;

    • Invasion of the myometrium by hydropic chorionic villi, accompanied by proliferation of both cytotrophoblast and syncytiotrophoblast;

    • May have local destruction and invasion of parametrial tissue and blood vessels.

  • Clinical outcome: Hydropic villi may embolize to distant sites, such as lungs and brain, but do not grow in these organs as true metastases, and even before the advent of chemotherapy, they eventually regressed unless fatal hemorrhage occurred; responds well to chemotherapy.

INTERMEDIATE TROPHOBLASTIC TUMORS

  • In contrast to syncytial cytotrophoblast, which is present on the chorionic villi, intermediate trophoblast is found in the implantation site and placental membranes. Intermediate trophoblast is composed of mononuclear cells with abundant cytoplasm that distinguish them from the syncytial cytotrophoblast.

  • In contrast to syncytiotrophoblasts (which produce HCG), intermediate trophoblast cells are weakly immunoreactive for human placental lactogen.

  • Including placental site trophoblastic tumor (PSTT) and epithelioid trophoblastic tumor.

  • Both have similar intermediate trophoblastic cells, but in PSTT, the cells form diffuse masses without significant necrosis that infiltrate the myometrium, and in epithelioid trophoblastic tumors the cells form nodules with abundant hyaline material.

PLACENTAL SITE TROPHOBLASTIC TUMOR (PSTT)

  • General Features: PSTT is a neoplastic proliferation of extravillous trophoblasts, forming a variable cellular mass that invades theendometrium and myometrium. PSTTs comprise < 2% of gestational trophoblastic neoplasms and present as neoplastic polygonal cells infiltrating the endomyometrium.

  • Clinical Features:

    • The clinical presentation is generally that of a young woman who has a recent history of pregnancy, although the tumor may occur in older women. Typically and interestingly, most PSTTs happen after a female gestation.

    • PSTTs may be preceded by a normal pregnancy (1/2), spontaneous abortion (1/6), or hydatidiform mole (1/5).

    • Mild to moderate elevation of hCG is characteristic, and the hormone quickly drops off after a hysterectomy.

  • Pathology Diagnosis:

    • The diagnosis is often suspected in an endometrial biopsy or curettage, and a uterine mass is seen upon ultrasound examination. The ultimate diagnosis is generally made in a hysterectomy specimen.

    • The key diagnostic feature of PSTT is the myometrial infiltrate consisting of intermediate-type trophoblasts. Most of the neoplastic cells are mononucleate, but binucleate, trinucleate, and multinucleated cells are usually present. As in the normal implantation site, the cells at the periphery of the tumor typically infiltrate between muscle fibers and bundles as single and small groups of cells without producing extensive necrosis. Recapitulating the normal implantation site trophoblasts, PSTT displays a pattern of vascular invasion.

    • Distinction of PSTTs from normal exaggerated placental implantation site trophoblast may be difficult and can be achieved by using biomarkers (Mel-Cam and Ki-67) that detect increased proliferation in the trophoblastic cells.

  • Immuhistochemistry Stains: Characteristically, the tumor cells are positive for hPL and focally positive for HCG.

  • Prognosis: Most cases of PSTT are clinically benign, with cure by hysterectomy. However, in up to 15% of cases, the tumor may persist and metastasize. Patients with localized (Stage I or II) disease or a less than 2-year interval from the prior pregnancy to diagnosis have an excellent prognosis. Tumors diagnosed 4 or more years following pregnancy, with lung involvement or with advanced stage have a poor prognosis. Overall, about 10% result in disseminated metastases and death.

CHORIOCARCINOMA IN SITU
 

CHORIOCARCINOMA

  • Incidence:1 in 20,000 to 30,000 pregnancies in us, much more common in some African countries, 1 in 2500 pregnancies in Ibadan, Nigeria.

  • Risk factors: 50% arise in hydatidiform moles, 25% in previous abortions, approximately 22% in normal pregnancies (intraplacental choriocarcinoma). The remainder occur in ectopic pregnancies and genital and extragenital teratomas. About 1 in 40 hydatidiform moles may give rise to a choriocarcinoma, in contrast to 1 in approximately 150,000 normal pregnancies.

  • Clinical: The uterine choriocarcinoma does not classically produce a large, bulky mass. It becomes manifest only by irregular spotting of a bloody, brown, sometimes foul-smelling fluid. This discharge may appear in the course of an apparently normal pregnancy, after a miscarriage, or after a curettage. Sometimes the tumor does not appear until months after these events. Usually, by the time the tumor is discovered locally, radiographs of the chest and bones already disclose the presence of metastatic lesions. The titers of HCG are elevated to levels above those encountered in hydatidiform moles. Occasional tumors, however, produce little hormone, and some tumors have become so necrotic as to become functionally inactive. Widespread metastases are characteristic of these tumors. Favored sites of involvement are the lungs (50%) and vagina (30% to 40%), followed in descending order of frequency by the brain, liver, and kidney.

  • Gross Morphology: classically a soft, fleshy, yellow-white tumor with a marked tendency to form large pale areas of ischemic necrosis, foci of cystic softening, and extensive hemorrhag.

  • Microscopic Morphology: a purely epithelial tumor, does not produce chorionic villi, grows by the abnormal proliferation of both cytotrophoblast and syncytiotrophoblast. The tumor invades the underlying myometrium, frequently penetrates blood vessels and lymphatics, and may extend out onto the uterine serosa and adjacent structures. In its rapid growth, it is subject to hemorrhage, ischemic necrosis, and secondary inflammation. In fatal cases, metastases are found in the lungs, brain, bone marrow, liver, and other organs. On occasion, metastatic choriocarcinoma is discovered without a detectable primary in the uterus (or ovary), presumably because the primary has undergone total necrosis.