Endometrial Lesions, Unusual Tumors, and Extrauterine cancer
Fig. 10.40 Endometrial complex hyperplasia with cytologic atypia.
Direct endometrial sampling (Papanicoloau x LP). This cellular fragment
shows another pattern of atypical hyperplasia—a cell clump with an irregular
as well and were identified in 41% of cases in an autopsy series.94
The role of cytology in the diagnosis of lymphoid neoplasms
is further diminished by the usual submucosal location of the
neoplastic cells. Ulceration is not common with these usu-
ally slow-growing lesions but when present the abnormal cells
are more easily detected.95 In one study 41% of women with
primary cervical lymphoma had abnormal cervical cytology.93
Primary genital tract lymphomas have been reported in
women from ages 20 to 80 years, although the majority are pre-
menopausal.93 Cervical lymphoma usually presents with vaginal
bleeding or as a pelvic mass but many women are asymptomatic.
When clinically apparent the cervix is usually diffusely enlarged
or a polypoid mass is present. Systemic symptoms are uncom-
mon with primary genital lesions.95 The prognosis of extranodal
lymphomas including those primarily involving the genital tract
is comparatively worse than nodal varieties, likely due to delays
in the diagnosis of these uncommon lesions.93
Lymphomas are traditionally divided into Hodgkin and non-
Hodgkin types. A discussion of classifications systems is beyond
the scope of this chapter and the reader is referred to other
sources. Hodgkin disease has been detected in cervical cytology,
albeit rarely.96 In these reported cases, the classic Reed Sternberg
cell with its distinctive binucleated appearance is present in a
background of mixed inflammatory cells. Non-Hodgkin lym-
phoma may present in exfoliative cytology as a monomorphic
pattern of dispersed single cells.93, 95 The small lymphocytic types
have scant cytoplasm and eccentric nuclei often with coarse
chromatin and prominent nucleoli. The large cell variants have
increased nuclear size and some cells may demonstrate nuclear
It is not uncommon to find large numbers of lymphocytes in
cervicovaginal cytology. When the lymphocytes overwhelm the
specimen a diagnosis of marked chronic cervicitis or follicular
cervicitis may be considered. In these cases a careful search for
a mixed inflammatory pattern with tingible body macrophages
and neutrophils will aid in distinguishing this reactive condi-
tion from a lymphoid neoplasm. Poorly differentiated and small
cell carcinomas that present as dispersed atypical cells may also
mimic lymphoid proliferations. Even poorly differentiated car-
cinomas will often show some degree of cohesion or nuclear
moulding as evidence of their epithelial nature. An advantage of
liquid-based preparations is the ability to perform immunophe-
notyping to distinguish an epithelial from a lymphoid origin.
However, in most cases biopsy confirmation is needed.
Malignant Melanoma
primary and
involve the uterine body and cervix. The cytology findings of
melanoma in either exfoliative or direct endometrial sampling
specimens are similar or identical to other sites in the body.97
Since melanoma may present with either epithelioid and/or
spindled features, the differential diagnosis in the uterus usually
includes poorly differentiated carcinoma and sarcoma.98 The
identification of intracellular melanin and the application of
an immunohistochemical panel (e.g. S-100, HMB-45, MART-1)
may be important in this regard. The exfoliative cytology of epi-
thelioid melanoma is characterized by discohesive large malig-
nant cells with abundant eosinophilic cytoplasm, and a round
to ovoid nucleus with a prominent nucleolus (Fig. 10.41). Direct
endometrial sampling may identify metastatic melanoma to the
body of the uterus.99
Trophoblastic Neoplasia
The neoplasms that arise from the trophoblastic cells of the
placenta fall into a broad spectrum of changes termed gesta-
tional trophoblastic disease (GTD). The incidence of GTD varies
worldwide but it is estimated to be associated with only 1 in
2000 pregnancies in North America.100 GTD can present either
during or after a pregnancy, sometimes occurring years after the
gestation. Most forms of GTD involve proliferation of the tro-
phoblastic cells that produce human chorionic gonadotrophin
(|3HCG), a marker that can be used to detect and follow the
presence of disease.
The most commonly recognized entities of GTD are hyda-
tidiform moles and choriocarcinoma. For a complete review
of GTD the reader is referred to other sources.101 Hydatidiform
moles are essentially abnormal placentas that have unusu-
ally shaped hydropic chorionic villi and proliferating tropho-
blast. In complete moles the villi are cystically dilated and the
proliferation is diffuse. In partial moles the villi show both
small sclerotic forms and dilated forms, and in addition an
abnormal fetus may develop. Both of these types of hydatidi-
form moles are usually evacuated and diagnosed by histologic
examination, and have a high cure rate, but persistence of the
trophoblastic tissue may occur as demonstrated by persistently
previous page 267 ComprehensiveCytopathology 1104p 2008 read online next page 269 ComprehensiveCytopathology 1104p 2008 read online Home Toggle text on/off