NEW FRONTIERS IN PATHOLOGY Case 1 Gynecological Pathology

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NEW FRONTIERS IN PATHOLOGYCase 1Gynecological
Pathology

• Kathleen R. Cho, M.D.

kathcho_at_umich.edu
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History

• 20 yo G4P1 woman was referred for management of
  two abnormal pap smears a few months after normal
  vaginal delivery at term
• Colposcopy showed aceto-white staining of entire
  transformation zone, abnormal vascular pattern
• Testing for high-risk HPV types negative
• Cervical biopsies were obtained

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AE1/AE3/CAM5.2
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p63
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p16
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hCG
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hPL
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Inhibin
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Ki67
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Dx Epithelioid Trophoblastic Tumor
Additional History

• Cone biopsy was performed and showed residual ETT
  extending to endocervical margin
• ETT also present in concurrent endocervical
  curettings
• No residual tumor identified in subsequent
  hysterectomy
• Patient lost to follow-up (no news is good news?)

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Epithelioid Trophoblastic Tumor

• Term first introduced by Mazur and Kurman
  (Blausteins Pathology of the Female Genital
  Tract, 4th ed, 1994)
• First series (n14) reported by Shih and Kurman,
  1998
• ETT now widely accepted as distinct diagnostic
  entity within the spectrum of gestational
  trophoblastic tumors

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Clinical Features

• Patients usually premenopausal (mean age 38),
  rarely postmenopausal
• Usually present with abnormal vaginal bleeding
• Serum hCG is elevated (broad range, usually not
  markedly elevated)
• Associated with previous pregnancy, often remote
  (mean 76 mos.)
• Associated with previous molar pregnancy (36)
• 13 of patients reported dead from disease, but
  overall survival/recurrence statistics unclear
  (rare tumor, poor follow-up)

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Pathologic Features - Gross

• Discrete solid and cystic masses in uterine
  fundus, lower uterine segment, or endocervix
  (approx. half in LUS or Cx)
• Variable amounts of hemorrhage and necrosis
• May present in extra-uterine locations without
  demonstrable uterine disease (small bowel, lung)

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Pathologic Features - Microscopic

• Generally circumscribed but foci of infiltrating
  cells often present at tumor periphery
• Relatively uniform population of trophoblastic
  cells with single nucleus
• Geographic necrosis often present
• Cells usually arranged in nests, cords and masses
  associated with eosinophilic, sometimes
  fibrillar, hyaline-like material (simulates
  keratin)

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Pathologic Features - Microscopic

• When cervix is involved, the tumor cells have a
  propensity to replace surface and endocervical
  glandular epithelium, simulating SIL
• Check clinical history for HPV-related lesions,
  HPV status, etc.
• May be mixed with areas resembling PSTT or
  choriocarcinoma
• Foci resembling placental site nodule (PSN) often
  present (PSN as possible precursor ??)

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Schematic representation of the trophoblastic
subpopulations in the placenta and fetal
membranes
IeM Shih and RJ Kurman, Int J Gynecol Pathol
2001 2031-47
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LESIONS OF INTERMEDIATE TROPHOBLAST
Exaggerated placental site (EPS) Placental site
trophoblastic tumor (PSTT)
IMPLANTATION SITE intermediate trophoblast
Villous intermediate trophoblast
CHORIONIC-TYPE intermediate trophoblast
Placental site nodule (PSN) Epithelioid
trophoblastic tumor (ETT)
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Immunostaining Algorithm for Trophoblastic Lesions
Modified from Shih and Kurman, Am J Surg Pathol,
281177-83, 2004
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n15 ITTs (8 PSTTs, 4 ETTs, 3 mixed
(ETT/PSTT/Choriocarcinoma) n11 Choriocarcinomas
(pure) n10 Cervical carcinomas (5 pure squamous
and 5 adenosquamous)
Note p16 positivity in cervical carcinomas is
strong, diffuse, and includes nuclear staining,
while staining in ITTs, when present, is usually
focal and cytoplasmic
Modified from Table 2, Immunohistochemical
Studies of Trophoblastic Tumors, N. Kalhor et
al., Am J Surg Pathol, 33633-638, 2009.
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Molecular Genetics of ETT

• Two studies have confirmed the trophoblastic
  (fetal) nature of ETTs
• Y chromosome markers
• Novel paternal alleles
• Analysis of small number of cases by comparative
  genomic hybridization failed to identify
  consistent chromosomal losses or gains

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ETT vs. PSTT

• PSTTs usually more infiltrative (less
  circumscribed)
• PSTT cells usually larger, more pleomorphic
• PSTT growth pattern is more sheet-like, rather
  than nests or cords
• PSTT displays characteristic invasion of vessel
  walls

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ETT vs. Choriocarcinoma

• ETTs lack the dimorphic population of trophoblast
  seen in choriocarcinomas
• Choriocarcinomas usually more hemorrhagic

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ETT vs. Placental Site Nodule

• PSNs usually microscopic (vs. ETT mass lesion)
• PSNs less cellular than ETTs
• PSNs more diffusely hyalinized
• PSNs not mitotically active
• Atypical PSNs ?

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SUMMARY

• ETT is a neoplasm of chorionic-type intermediate
  trophoblast
• Most cases behave in a benign fashion, but some
  do not
• Criteria allowing prediction of malignant
  behavior remain uncertain (? increased mitotic
  activity)
• ETT can closely mimic cervical squamous cell
  carcinomas
• Dx usually straightforward if given consideration!