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138 Gestational Trophoblastic Neoplasms, Pathology of the Placenta
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Gestational Trophoblastic Neoplasms, Pathology of
the Placenta, Fig. 2 Gestational choriocarcinoma, with
characteristic blood lakes (a) and biphasic growth pattern
Molecular Features
As gestational choriocarcinoma is derived from
trophoblastic tissue with either androgenic DNA
only or with both maternal and paternal DNA
content, its gestational origin can be resolved
through short tandem repeat genotyping. As
many gestational choriocarcioma arise following
a complete hydatidiform molar pregnancy, the
vast majority show androgenic DNA only
(Savage et al. 2017).
Differential Diagnosis
In most cases, the presence of a biphasic population
of malignant mononuclear and syncytiotrophoblast
makes identification of choriocarcinoma a somewhat routine diagnosis. However, in challenging
cases (particularly those with minimal tissue for
evaluation), the diagnosis may be more difficult.
It may be exceedingly difficult to differentiate gestational choriocarcinoma from an early pregnancy
or hydatidiform molar pregnancy, particularly in
cases where only minimal detached fragments of
tissue composed of a biphasic trophoblast population are identified. In this scenario, identification of
marked cytologic atypia, mitotic figures, or nonischemic necrosis would favor a diagnosis of
choriocarcinoma.
Separation of gestational choriocarcioma from
ETT and PSTT is predominantly based on morphologic findings, the details of which are
discussed in detail in the preceding sections covering these two entities.
with mononuclear trophoblast wrapped by peripheral
multinucleate syncytiotrophoblast (b)
The monomorphic variant of gestational choriocarcinoma may show considerable morphologic overlap with a poorly differentiated
carcinoma, with diffuse expression of
cytokeratins by immunohistochemistry in both
tumor types serving as a potential diagnostic pitfall. However, correlation with the patient’s history may reveal an abnormal antecedent
pregnancy or abnormal elevation in serum hCG,
either of which should raise suspicion for choriocarcinoma. In challenging cases, short tandem
repeat genotyping may be required.
Mixed Trophoblastic Tumors
Definition
Mixed trophoblastic tumors are gestational trophoblastic neoplasms that contain a distinct component of at least two histologic categories of
gestational trophoblastic tumor: gestational choriocarcinoma, placental site trophoblastic tumor
(PSTT), and/or epithelioid trophoblastic tumor
(ETT). Mixed trophoblastic tumors share many
of their clinicopathologic features with the individual trophoblastic tumor components from
which the tumor is derived.
Clinical Features
• Incidence
The true incidence of mixed trophoblastic is
uncertain given their extreme rarity.
Gestational Trophoblastic Neoplasms, Pathology of the Placenta 139
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• Age
Mixed trophoblastic tumors are typically identified in patients of reproductive age and occasionally in postmenopausal patients (Borden
et al. 2019; Cole et al. 2008; Gari 2015; Mao
et al. 2007; Ramonde tta et al. 2002; Shih and
Kurman 1998b; Tse et al. 2018; Zhang et al.
2015).
• Sex
Female.
• Site
Mixed trophoblastic tumors are most commonly identified in the uterus.
• Treatment
Given the rarity of mixed trophoblastic tumors,
no specific treatment algorithm has been developed for these tumors and they are treated
based on the management guidelines for the
individual components that comprise the
mixed tumor.
• Outcome
The outcome of mixed trophoblastic tumors
mirrors the clinical behavior of the individual
components that comprise the tumor, with
mixed ETT/PSTT showing more indolent
behavior than mixed trophoblastic tumors
with a component of choriocarcinoma (Cole
et al. 2008; Shih and Kurman 1998a;Tse
et al. 2018).
Macroscopy
The gross pathologic findings of a mixed trophoblastic tumor reflect the typical gross pathologic
findings of the individual components of the
mixed tumor.
Microscopy
The morphology of mixed trophoblastic tumors
mirror that of the individual components that comprise the tumor. In the literature, mixed ETT and
choriocarcinoma is most common, followed by
mixed ETT and PSTT. Tumors with a mixture of
ETT, PSTT, and choriocarcinoma are exceedingly
rare (Borden et al. 2019;Coleetal.2008;Gari
2015; Ramondetta et al. 2002;ShihandKurman
1998a; Tse et al. 2018; Zhang et al. 2015).
Immunophenotype
The immunophenotype of mixed trophoblastic
tumors mirror the immunophenotype of the individual components that comprise the tumor.
Molecular Features
STR genotyping can be used to confirm the gestational origin of mixed trophoblastic tumors.
Differential Diagnosis
The differential diagnosis for a mixed trophoblastic tumor mirrors the differential diagnosis
discussed for each of the possible components of
a mixed tumor; please refer to the appropriate
section headers for details.
Placental Site Trophoblastic Tumor
Definition
Placental site trophoblastic tumor (PSTT) is a
malignant gestational trophoblastic neoplasm
composed of implantation site intermediate
trophoblast.
Clinical Features
• Incidence
PSTT is rare, accounting for between <1% and
2% of gestational trophoblastic tumors with an
estimated incidence rate of 1.0 per 100,000
deliveries (Lybol et al. 2011). Although both
PSTT and exaggerated placental site (EPS) are
derived from implantation site intermediate tro-
phoblast, existing data suggests that PSTT does
not represent malignant transformation of EPS.
• Age
PSTT are identified in patients who have
reached reproductive age and may occur in
postmenopausal patients (range: 20–62 years;
mean: 31 years) (Baergen et al. 2006; Lybol
et al. 2011; Papadopoulos et al. 2002). The
preceding gestation is most commonly a full-
term viable pregnancy (>50%), hydatidiform
mole (up to 21%), or spontaneous abortion
(Papadopoulos et al. 2002). The latency inter-
val following the prior gestation is
G
140 Gestational Trophoblastic Neoplasms, Pathology of the Placenta
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8–34 months. Presenting symptoms are often
nonspecific and include vaginal bleeding
(>75%), uterine enlargement, and
abdominopelvic pain. Serum hCG levels typically show only modest elevation, typically
<1000 mIU/mL but occasionally as high as
50,000 mIU/mL (Hassadia et al. 2005;
Papadopoulos et al. 2002).
• Sex
Female.
• Site
PSTTs typically involve the uterine corpus or
lower uterine segment and are confined to the
uterus at presentation in the vast majority of
cases, although some patients present with
extrauterine spread to the pelvis or lungs
(Papadopoulos et al. 2002).
• Treatment
In cases of PSTT confined to the uterus, hysterectomy is the treatment of choice and is
curative in the majority of cases. Pelvic
lymph nodes dissection may be performed if
there is clinical suspicion for extensive
myometrial invasion or other high-risk features. If future fertility is desired, thorough
curettage or local excision may be considered.
Following surgical resection, systemic chemotherapy may be considered for tumor showing
high-risk features (interval from index pregnancy greater than 2 years, deep myometrial
invasion, necrosis, >5 mitotic figures per
10 HPF). Patients with known extrauterine disease are typically offered systemic chemotherapy, although chemotherapy resistance is
common (Baergen et al. 2006; Hassadia et al.
2005; Papadopoulos et al. 2002). In all cases,
hCG levels will be monitored to assess for
possible disease recurrence/progression.
• Outcome
For the majority of patients, hysterectomy is
curative. However, between 15 and 30% of
patients with PSTT will develop recurrent/metastatic disease and an overall mortality rate of
10% (Hassadia et al. 2005; Papadopoulos et al.
2002). Clinicopathologic features that have
been associated with adverse outcomes include
interval from index pregnancy greater than
2 years, deep myometrial invasion, necrosis,
>5 mitotic figures per 10 HPF, age > 40 years,
and tumor cells with clear cytoplasm (Baergen
et al. 2006; Hassadia et al. 2005; Papadopoulos
et al. 2002).
Macroscopy
PSTT typically form a solitary mass (average size
5 cm) with a soft, tan, solid cut surface with focal
areas of hemorrhage and necrosis, and may penetrate the full thickness of the uterine wall (Baergen
et al. 2006).
Microscopy
PTTs are composed of implantation-type intermediate trophoblast that centrally forms large aggregates or exhibit sheet-like growth, with the tumor
cells at the periphery of the lesion infiltrating
through the myometrium and splaying apart fascicles of smooth muscle or infiltrating between individual smooth muscle cells. The tumor cells are
more pleomorphic than those of ETT and exhibit
atypical, enlarged, hyperchromatic nuclei and
moderate-to-abundant amphophilic or densely
eosinophilic cytoplasm. Scattered multinucleate
forms may be present. Often, the tumor cells
exhibit a spindle cell morphology. Mitotic figures
are mildly increased (average 5 per 10 HPF), but
may be variable or inconspicuous (Baergen et al.
2006). Although necrosis is often present, this find-
ing may be focal or absent in some cases. As with
other trophoblastic neoplasms, the tumor cells are
often embedded within an eosinophilic, fibrillar,
hyaline-like material that may mimic necrosis.
PSTT show a characteristic pattern of vascular
invasion, with tumor cells invading and replacing
the normal blood vessel wall in a manner than is
reminiscent of remodeled vasculature in a nonneoplastic placental implantation site. In contrast
to a nonneoplastic placental implantation site,
chorionic villi are not expected in PSTT (Fig. 3).
Immunophenotype
PSTTs show strong immunoexpression of pantrophoblast markers (cytokeratins, α-inhibin,
GATA3, and PLAP) and demonstrate evidence
of implantation-type intermediate trophoblastic
differentiation (strong staining for hPL with
weak-to-absent expression of p63). PSTTs show
Gestational Trophoblastic Neoplasms, Pathology of the Placenta 141
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Gestational Trophoblastic Neoplasms, Pathology of
the Placenta, Fig. 3 Placental site trophoblastic tumor,
with sheets of trophoblast infiltrating between smooth
an increased proliferation index (>8%) with an
average proliferation index of 14% by ki67 (Shih
2007; Shih and Kurman 1998b).
Molecular Features
The gestational origin of PSTT can be resolved
through short tandem repeat genotyping. PSTT is
often associated with a preceding female gestation
and the majority of cases lack genetic evidence of
DNA from the Y chromosome, sugges ting that the
paternally derived X chromosome plays a major
role in pathogenesis (Hui et al. 2000).
Differential Diagnosis
As with other gestational trophoblastic proliferations, PSTT may show considerable morphologic
overlap with other gestational trophoblastic proliferations (benign or malignant) as well as epithelial
or mesenchymal tumors of the gynecologic tract.
The differential diagnosis of PSTT vs EPS and
PSTT vs ETT was previously discussed; please
refer to the Exaggerated Placental Site Reaction
and Epithelioid Trophoblastic Tumor section for
details.
PSTT often show admixed mononuclear and
multinucleate trophoblast that may mimic the
biphasic trophoblast population of choriocarcinoma.
However, the multinucleate trophoblast cells in
PSTT are admixed haphazardly within the tumor
and lack the lacy appearance and peripheral location
muscle fibers (a) and replacing/remodeling native blood
G
vessels. (b) Numerous mitotic figures are also present
of the syncytiotrophoblast of choriocarcinoma.
Although PSTT typically exp resses hPL to a greater
extent than choriocarcinoma, hCG is of little utility
as the multinucleate cells in both will express hCG.
However, PSTT and choriocarcinoma show disparate proliferation index by ki67, with PSTT showing
a proliferation index of ~20%, far less than the
proliferation index of ~70% typical of choriocarcinoma (Shih and Kurman 1998b).
The differential diagnosis of PSTT also
includes somatic tumors outside of the category
of gestational trophoblastic neoplasms. This differential diagnosis is quite similar to that previously discussed in the differential diagnosis of
ETT; please refer to that section for details. However, it should be noted that the typical implantation site-like vascular involvement of PSTT may
be helpful in differentiating PSTT from other epithelioid malignancies. In cases in which both
PSTT or somatic malignancy are diagnostic considerations, short tandem repeat genotyping may
be required.
References
Alazzam,M.,Tidy,J.,Osborne,R.,Coleman,R.,Hancock,
B. W., & Lawrie, T. A. (2016). Chemotherapy for resis-
tant or recurrent gestational trophoblastic neoplasia.
Cochrane Database of Systematic Reviews, 1, CD00889
1. https://doi.or g/10.1002 /14651858.CD008 891.pub3.
142 Gestational Trophoblastic Neoplasms, Pathology of the Placenta
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Baergen, R. N., Rutgers, J. L., Young, R. H., Osann, K., &
Scully, R. E. (2006). Placental site trophoblastic tumor:
A study of 55 cases and review of the literature emphasizing factors of prognostic significance. Gynecologic
Oncology, 100(3), 511–520. https://doi.org/10.1016/j.
ygyno.2005.08.058.
Borden, L. E., McCuin, E. S., Sheth, P. D., & Iglesias,
D. A. (2019). Rare case of mixed metastatic placental
site trophoblastic tumor and choriocarcinoma. Journal
of Oncology Practice/ American Society of Clinical
Oncology, 15(9), 505–506. https://doi.org/10.1200/
JOP.19.00110.
Cole, M. E., Broaddus, R., Thaker, P., Landen, C., &
Freedman, R. S. (2008). Placental-site trophoblastic
tumors: A case of resistant pulmonary metastasis.
Nature Clinical Practice. Oncology, 5(3), 171–175.
https://doi.org/10.1038/ncponc1042.
Davis, M. R., Howitt, B. E., Quade, B. J., Crum, C. P.,
Horowitz, N. S., Goldstein, D. P., & Berkowitz, R. S.
(2015). Epithelioid trophoblastic tumor: A single institution case series at the New England Trophoblastic Disease
Center. Gynecologic Oncology, 137(3), 456–461. https://
doi.org/10.1016/j.ygyno.2015.03.006.
Fadare, O., Parkash, V., Carcangiu, M. L., & Hui,
P. (2006). Epithelioid trophoblastic tumor: Clinicopathological features with an emphasis on uterine cervical
involvement. Modern Pathology, 19(1), 75–82. https://
doi.org/10.1038/modpathol.3800485.
Gari, A. (2015). Placental site trophoblastic tumor and
choriocarcinoma: An unusual presentation. BMC
Research Notes, 8, 703. https://doi.org/10.1186/
s13104-015-1693-8.
Hassadia, A., Gillespie, A., Tidy, J., Everard, R. G. N. J.,
Wells, M., Coleman, R., & Hancock, B. (2005). Placental site trophoblastic tumour: Clinical features and
management. Gynecologic Oncology, 99(3), 603–607.
https://doi.org/10.1016/j.ygyno.2005.06.054.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4525957/
pdf/ijcep0008-7254.pdf.
Hui, P. (2019). Gestational trophoblastic tumors: A timely
review of diagnostic pathology. Archives of Pathology
& Laboratory Medicine, 143(1), 65–74. https://doi.org/
10.5858/arpa.2018-0234-RA.
Hui, P., Parkash, V., Perkins, A. S., & Carcangiu, M. L.
(2000). Pathogenesis of placental site trophoblastic
tumor may require the presence of a paternally derived
X chromosome. Laboratory Investigation, 80(6),
965–972. https://doi.org/10.1038/labinvest.3780099.
Jiao, L., Ghorani, E., Sebire, N. J., & Seckl, M. J. (2016).
Intraplacental choriocarcinoma: Systematic review and
management guidance. Gynecologic Oncology, 141(3),
624–631.
Lybol, C., Thomas, C. M., Bulten, J., van Dijck, J. A.,
Sweep, F. C., & Massuger, L. F. (2011). Increase in the
incidence of gestational trophoblastic disease in The
Netherlands. Gynecologic Oncology, 121(2), 334–338.
https://doi.org/10.1016/j.ygyno.2011.01.002.
Mao, T. L., Kurman, R. J., Huang, C. C., Lin, M. C., &
Shih Ie, M. (2007). Immunohistochemistry of
https://doi.org/10.1016/j.ygyno.2016.03.026.
choriocarcinoma: An aid in differential diagnosis and
in elucidating pathogenesis. The American Journal of
Surgical Pathology, 31(11), 1726–1732. https://doi.
org/10.1097/PAS.0b013e318058a529.
Papadopoulos, A. J., Foskett, M., Seckl, M. J., McNeish, I.,
Paradinas, F. J., Rees, H., & Newlands, E. S. (2002).
Twenty-five years’ clinical experience with placental
site trophoblastic tumors. The Journal of Reproductive
Medicine, 47(6), 460–464. https://www.ncbi.nlm.nih.
gov/pubmed/12092014.
Ramondetta, L. M., Silva, E. G., Levenback, C. F., &
Burke, T. W. (2002). Mixed choriocarcinoma in a post-
menopausal patient. International Journal of Gyneco-
logical Cancer, 12(3), 312–316. https://doi.org/10.
1046/j.1525-1438.2002.01110.x.
Savage,J.,Adams,E.,Veras,E.,Murphy,K.M.,&
Ronnett, B. M. (2017). Choriocarcinoma in women:
Analysis of a case series with genotyping. The Amer-
ican Journal of Surgical Pathology, 41(12),
1593– 1606. https://doi.org/10.1097/PAS.
0000000000000937.
Shih, I. M. (2007). Trophogram, an
immunohistochemistry-based algorithmic approach,
in the differential diagnosis of trophoblastic tumors
and tumorlike lesions. Annals of Diagnostic Pathology,
11(3), 228–234. https://doi.org/10.1016/j.anndiagpath.
2007.04.001.
Shih, I. M., & Kurman, R. J. (1998a). Epithelioid tropho-
blastic tumor: A neoplasm distinct from choriocarci-
noma and placental site trophoblastic tumor simulating
carcinoma. The American Journal of Surgical Pathol-
ogy, 22(11), 1393–1403. https://doi.org/10.1097/
00000478-199811000-00010.
Shih, I. M., & Kurman, R. J. (1998b). Ki-67 labeling index
in the differential diagnosis of exaggerated placental
site, placental site trophoblastic tumor, and choriocar-
cinoma: a double immunohistochemical staining tech-
nique using Ki-67 and Mel-CAM antibodies. Human
Pathology, 29(1), 27–33. https://doi.org/10.1016/
s0046-8177(98)90386-0.
Tse, K. Y., Chiu, K. W. H., Chan, K. K. L., Chu, M. M. Y.,
Ngu, S. F., Cheung, A. N. Y., Ngan, H. Y. S., & Ip,
P. P. C. (2018). A case series of five patients with pure
or mixed gestational epithelioid trophoblastic tumors
and a literature review on mixed tumors. American
Journal of Clinical Pathology, 150(4), 318–332.
https://doi.org/10.1093/ajcp/aqy039.
Zhang, X., Lu, W., & Lu, B. (2013). Epithelioid tropho-
blastic tumor: An outcome-based literature review of
78 reported cases. International Journal of Gynecolog-
ical Cancer, 23(7), 1334–1338. https://doi.org/10.
1097/IGC.0b013e31829ea023.
Zhang, X., Zhou, C., Yu, M., & Chen, X. (2015).
Coexisting epithelioid trophoblastic tumor and placen-
tal site trophoblastic tumor of the uterus following a
term pregnancy: Report of a case and review of litera-
ture. International Journal of Clinical and Experimen-
tal Pathology, 8(6), 7254–7259. https://www.ncbi.nlm.
nih.gov/pubmed/26261623.
Glandular Tumors and Precursors, Pathology of the Vagina 143
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Microscopy
Glandular Tumors and
Precursors, Pathology of the
Vagina
Raji Ganesan
Birmingham Women’s and Children’s NHS Trust,
Birmingham, UK
Precursor lesions for adenocarcinoma are not
described in the vagina. Vaginal adenosis
(discussed elsewhere) maybe a precursor of
some adenocarcinomas.
These carcinomas show microscopic features
like HPV-associated cervical adenocarcinomas
with papillary, villoglandular, and/or glandular
architecture. The lining columnar cells have
crowded, cigar-shaped, irregular nuclei. Apical
mitoses and apoptotic bodies were easily
identified.
Immunophenotype
P16 shows block positive staining.
Molecular Features
The cases described were positive for high-risk
HPV by in situ hybridization or polymerase chain
reaction.
HPV-Associated Adenocarcinoma of the
Vagina
Definition
This is an HPV-associated glandular malignancy
that shows stromal invasion with/without an exophytic component. Synchronous or previous history of cervical adenocarcinoma must be excluded.
Differential Diagnosis
The main differential diagnoses are HPVindependent adenocarcinoma and metastatic
HPV-associated cervical adenocarcinomas.
HPV-Independent Adenocarcinoma
G
Clinical Features
The presenting symptoms are related to a vaginal
mass.
• Incidence
These are extremely rare tumors with a single
series of four cases reported in literature
(Voltaggio et al. 2020).
• Age
The age range noted is between 38 and
51 years.
• Site
Vagina.
• Treatment
Surgical excision.
• Outcome
In the small series available, one recurrence
was noted but no metastatic disease was
recorded.
Macroscopy
The reporte d cases presented as polypoid
masses.
Endometrioid Carcinoma of the Vagina
Refer details below.
Definition
It is a primary vaginal adenocarcinoma with features similar to endometrioid endometrial
adenocarcinoma.
Clinical Features
Most common presenting feature is abnormal
vaginal bleeding. Most women have a history of
previous hysterectomy.
• Incidence
Uncommon.
• Age
In the largest reported case series (Staats et al.
2007), the mean age was 60 years.
• Site
Upper vagina.
• Treatment
Primary excision with adjuvant chemo- or
radiotherapy.
144 Glandular Tumors and Precursors, Pathology of the Vagina
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• Outcome
In stage I disease, recurrence was seen in 20%
of cases, and there was no distant disease or
death.
Macroscopy
Most tumors are polypoid or papillary.
Microscopy
Commonly the tumors have tubular glands lined
by columnar cells with a moderate amount of
eosinophilic cytoplasm. Focal mucinous differentiation, squamous metaplasia, and a small nonvillous papillary component can be seen.
Typically endometriosis can be seen and maybe
contiguous with the carcinoma.
Immunophenotype
Not described.
Molecular Features
Not described.
Differential Diagnosis
Metastatic adenocarcinoma, other types of primary vaginal adenocarcinoma, and variants of
endometriosis.
markedly declined. It is now more common
in older women.
• Site
Upper third of vagina.
• Treatment
Local excision followed by adjuvant chemo or
radiotherapy.
• Outcome
Recurrence can be seen in about 25% of cases.
Ten-year survival rates are better in tumors
related to DES exposure (Waggoner
et al. 1994).
Macroscopy
Mostly seen as polypoid or exophytic masses.
Microscopy
The histological features are similar to clear cell
carcinomas elsewhere in the gynecological tract,
with a greater proportion of tubulocystic and papillary patterns. Stromal hyalinizat ion, eosinophilic
hyaline globules, and hobnail cells can be seen.
Immunophenotype
Similar to clear cell carcinomas elsewhere in the
gynecological tract with positive staining for
HNF1 beta and Napsin A (Talia et al. 2019).
Clear Cell Carcinoma of the Vagina
Refer details below.
Definition
It is a primary vaginal adenocarcinoma with features similar clear cell carcinoma elsewhere.
Clinical Features
Abnormal vaginal bleeding.
• Incidence
A rare tumor although the commonest primary
vaginal adenocarcinoma.
• Age
In the DES (diethylstilbestrol) era, this was a
tumor of young women (Herbst et al. 1972).
They were associated with adenosis in women
exposed to DES in utero. Since the discontinuation of DES use during pregnancy, the incidence of vaginal clear cell carcinomas has
Differential Diagnosis
Morphologic evaluation usually permits a correct
diagnosis, but metastatic clear cell carcinoma
must be ruled out (Fig. 1).
Mucinous Carcinoma of the Vagina
Refer details below.
Definition
These are primary vaginal carcinomas exhibiting
gastric differentiation.
Clinical Features
In the largest series of 11 cases (Wong et al. 2018),
the presenting symptoms included abnormal
bleeding, vaginal discharge, and urinary symptoms secondary to the vaginal mass.
• Incidence
These are rare neoplasms.
Glandular Tumors and Precursors, Pathology of the Vagina 145
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Glandular Tumors and Precursors, Pathology of the
Vagina, Fig. 1 Clear cell carcinoma. (a) Papillary struc-
tures lined by atypical cells with clear cytoplasm and
• Age
The mean age of presentation is 56 years.
• Site
Anywhere in the vagina.
• Treatment
Surgical followed by adjuvant chemo- or
radiotherapy.
• Outcome
There is limited data.
Macroscopy
No specific appearance.
Microscopy
The malignant glands are mucinous and can show
goblet cell and neuroendocrine differentiation.
The mucinous cells have abundant clear/pale
cytoplasm with prominent cell membranes.
Adenosis may be seen in the background.
Immunophenotype
The cells are positive with CK7, CEA, CDX2,
HIK1083, MUC6 may be positive with CK20
and PAX8, and lack staining for hormone receptors. Mutation type staining with p53 can be seen
in up to 50% of cases (Talia et al. 2019).
Differential Diagnosis
Morphology and immunohistochemistry allow a
correct diagnosis. Association with adenosis
hobnailing of the nuclei. (b) The neoplastic cells lining
glands show cytoplasmic granular staining with Napsin A
favors a vaginal primary, but metastatic carcinoma
must be ruled out.
Other Rare Primary Carcinomas of the Vagina
These include intestina l type mucinous carcinoma, mesonephric carcinoma, and
carcinosarcoma.
References and Further Reading
Herbst, A. L., Kurman, R. J., Scully, R. E., & Poskanzer,
D. C. (1972). Clear-cell adenocarcinoma of the genital
tract in young females – registry report. New England
Journal of Medicine, 287(25), 1259–1264.
Staats, P. N., Clement, P. B., & Young, R. H. (2007).
Primary endometrioid adenocarcinoma of the vagina:
A clinicopathologic study of 18 cases. American Jour-
nal of Surgical Pathology, 31(10), 1490–1501.
Talia, K. L., Wong, R. W., & McCluggage, W. G. (2019).
Expression of markers of müllerian clear cell carci-
noma in primary cervical and vaginal gastric-type ade-
nocarcinomas. International Journal of Gynecological
Pathology, 38(3), 276–282.
Voltaggio, L., McCluggage, W. G., Iding, J. S., Martin, B.,
Longacre, T. A., & Ronnett, B. M. (2020). A novel
group of HPV-related adenocarcinomas of the lower
anogenital tract (vagina, vulva, and anorectum) in
women and men resembling HPV-related endocervical
adenocarcinomas. Modern Pathology, 33(5), 944–952.
Waggoner, S. E., Mittendorf, R., Biney, N., Anderson, D.,
& Herbst, A. L. (1994). Influence of in utero diethyl-
stilbestrol exposure on the prognosis and biologic
behavior of vaginal clear-cell adenocarcinoma. Gyne-
cologic Oncology, 55(2), 238–244.
G
146 Glandular Tumors and Precursors, Pathology of the Vulva
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Wong, R. W., Moore, M., Talia, K. L., Ganesan, R., &
McCluggage, W. G. (2018). Primary vaginal gastrictype adenocarcinoma and vaginal adenosis exhibiting
gastric differentiation: Report of a series with detailed
Immunohistochemical analysis. American Journal of
Surgical Pathology, 42(7), 958–970.
Glandular Tumors and
Precursors, Pathology of the
Vulva
Aleodor Andea
Department of Pathology, University of
Michigan, Ann Arbor, MI, USA
Adenocarcinoma of Mammary
Gland Type
Synonyms
Adenocarcinoma of anogenital mammary-like
glands; Adenocarcinoma of the vulva with breast
carcinoma features.
Definition
Adenocarcinoma of mammary gland type
(AMGT) is a carcinoma with variable morphology thought to arise from the anogenital
mammary-like glands from the vulva and characterized by morphologic and immunophenotypic
resemblance to breast carcinoma.
spread is relatively rare (Abbott and Ahmed
2006).
Macroscopy
Most common presentation is with a solitary nodule, 3–4 cm in diameter (Abbott and Ahmed 2006;
Kazakov et al. 2011).
Microscopy
Most cases demonstrate histologic features
resembling ductal carcinoma of the breast with
infiltrating ducts and cords of atypical cells
(Figs. 1 and 2). Both low-grade and high-grade
forms exist. An in situ component resembling
breast ductal carcinoma in situ (DCIS) may be
seen. Benign anogenital mammary-like glands
can be occasionall y appreciated next to the ca rcinoma. The ductal type can be associated with
extramammary Paget disease (Ohira et al. 2004).
A variant that resemble s lobular carcinoma of the
breast has been rarely reported (Kazakov et al.
2011). Few cases showing morphologic findings
of tubulo-lobular carcinoma, mucinous carcinoma, adenoid cystic carcinoma, and secretory
carcinoma have been reported (Kazakov et al.
2011; Nguyen et al. 2019;Fig.3).
Immunophenotype
AMGT demonstrates a similar immunophenotype
with the breast carcinoma of similar type. Most
tumors are positive for CK7, ER, PR, and GATA3.
Clinical Features
• Incidence
AMGT is rare with about 40 cases reported in
the literature (Desouki and Fadare 2021).
• Age
Most patients are postmenopausal.
• Site
Labia majora is the most common site.
• Treatment
Treatment modalities include radical or
hemivulvectomy (Kazakov et al. 2011).
• Outcome
AMGTs are locally aggressive tumors with
frequent regional metastases; however, distant
Glandular Tumors and Precursors, Pathology of the
Vulva, Fig. 1 AMGT low power shows an infiltrating
neoplasm set in a desmoplastic stroma
Glandular Tumors and Precursors, Pathology of the Vulva 147
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Bartholin Gland Carcinoma
Definition
Primary vulvar carcinoma arising from Bartholin
glands.
Clinical Features
• Incidence
Bartholin gland carcinomas (BGC) are rare
tumors, representing less than 5% of vulvar
neoplasms and under 1% of all female genital
Glandular Tumors and Precursors, Pathology of the
Vulva, Fig. 2 AMGT higher magnification shows glands
and cords of atypical cells infiltrating the dermis, resembling the histology of breast ductal carcinoma
Glandular Tumors and Precursors, Pathology of the
Vulva, Fig. 3 AMGT the tumor cells are positive for CK7
Molecular Features
Few studied cases show mutations in PIK3CA
(Konstantinova et al. 2017a). A case of secretory
carcinoma demonstrated the characteristic ETV6-
NTRK3 fusions encountered in the breast counterpart tumor (Nguyen et al. 2019).
Differential Diagnosis
AMGT must be distinguished from adnexal carcinomas involving the vulva such as
porocarcinoma or hidradenocarcinoma. AMGT
must also be differentiated from the rare instances
of a breast carcinoma metastatic to the vulva. In
these instances, identification of an in situ component favors a primary vulvar neoplasm.
tract malignancies (Lee et al. 2015; Nazeran
et al. 2019).
• Age
Middle age to elderly women with a mean age
of 53 years, younger than non-Bartholin-
related vulvar carcinomas (Bhalwal et al.
2016; Di Donato et al. 2017).
• Site
BGCs arise in the areas of Bartholin glands in
the posterolateral introitus.
• Treatment
Due to the rarity of BGC, guidelines for treat-
ment are not well established (Di Donato et al.
2017). Treatment usually includes wide local
excision, hemivulvectomy, or vulvectomy with
a subset of cases undergoing lymph node
biopsy. Adjuvant chemo or radiation therapy
are also used in some cases (Di Donato
et al. 2017).
• Outcome
BGC is an aggressive disease with a 5-year
recurrence rate of 40% (Bhalwal et al. 2016).
Most patients present with advanced disease
with the tumor already extending to adjacent
structures, regional lymph nodes, or distant
spread. Adenocarcinoma histology and posi-
tive lymph nodes are associated with worst
survival in multivariate analysis (Di Donato
et al. 2017).
Macroscopy
These tumors present usually as a well
circumscribed but unencapsulated nodule with
solid to cystic cut surfaces (Desouki and Fadare
2021). Average size in 3.8 cm (Desouki and
Fadare 2021).
G
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