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470 Non-trophoblastic Tumors of the Placenta, Pathology of the Placenta
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similar to their counterparts in the non-pregnant
setting.
Immunophenotype
The standard approach to immunohistochemical
evaluation of the tumor in the nonpregnant setting
applies in the setting of placental involvement.
Molecular Features
Not applicable.
Differential Diagnosis
Not applicable.
References and Further Reading
Baergen, R. N., Johnson, D., Moore, T., & Benirschke,
K. (1997). Metastatic melanoma to the placenta.
Archives of Pathology & Laboratory Medicine, 121,
508–511.
Las Heras, J., Leal, G., & Haust, M. D. (1986). Congenital
leukemia with placental involvement. Cancer, 58,
2278–2281.
Pavlidis, N., & Pentheroudakis, G. (2008). Metastatic
involvement of placenta and foetus in pregnant
women with cancer. Cancer and pregnancy
(pp. 183–194). Berlin/Heidelberg: Springer.
Potter, J. F., & Schoeneman, M. (1970). Metastasis of
maternal cancer to the placenta and fetus. Cancer, 25,
380–388.
O
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Other Carcinomas and
Undifferentiated Carcinoma,
Pathology of the Ovary
Laura Casey
Department of Cellular Pathology, The Royal
London Hospital, Barts Health NHS Trust,
London, UK
Mesonephric-Like Adenocarcinoma
Definition
A glandular tumor demonstrating mesonephric
differentiation.
Clinical Features
• Incidence
These tumors are extremely rare.
• Age
The majority of these tumors occur in post-
menopausal women (McFarland et al., 2016).
• Sex
Female.
• Site
Ovary.
• Clinical Associations/Risk Factors
Nil.
• Treatment
Primary cytoreductive surgery (tot al abdomi-
nal hysterectomy and bilateral salpingo-
oophorectomy with peritoneal staging).
• Outcome
These tumors arevery rare and there is,therefore,
insufficient data to predict clinical outcomes.
Macroscopy
Mesonephric-like tumors tend to be unilateral. They
vary in size (4–32 cm) and may be solid, cystic, or a
combinationofthetwo(McFarlandetal.,2016).
Microscopy
Mesonephric-like carcinomas may be tubular
(mesonephroid), ductal (pseudoendometrioid),
sieve-like, papillary, or solid in architecture. Several morphologies may be represented in the same
tumor. In the most common – tubular – variant,
eosinophilic colloid-like material may be present
within the gland lumina. Neither squamous nor
mucinous differentiation should be evident.
Tumor cells are mildly pleomorphic with either
vesicular or dense chromatin and occasional
prominent nucleoli. Mitotic activity varies from
inconspicuous to brisk (McFarland et al., 2016;
Pors et al., 2018) (Figs. 1 and 2).
Immunophenotype
These tumors are positive for GATA3, TTF1,
CD10 (luminal), and PAX8; are negative for ER,
PR, and WT1; and showwild-type p53 expression
(McFarland et al., 2016; Pors et al., 2018).
Molecular Features
Majority associated with KRAS mutations
(Mirkovic et al., 2015).
© Springer Nature Switzerland AG 2023
S. Stolnicu, R. Ali-Fehmi (eds.), Gynecologic Pathology, Encyclopedia of Pathology,
https://doi.org/10.1007/978-3-030-97378-0
472 Other Carcinomas and Undifferentiated Carcinoma, Pathology of the Ovary
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Undifferentiated and Dedifferentiated
Carcinomas of the Ovary
Definition
Dedifferentiated carcinoma is a biphasic tumor
composed of both a well-differentiated and an
undifferentiated component. An undifferentiated
carcinoma is a malignant epithelial tumor whose
lineage cannot be determined morphologically or
immunohistochemically.
Clinical Features
• Incidence
Uncommon tumors accounting for 0.5% of all
ovarian carcinomas (Köbel et al., 2010).
• Age
Other Carcinomas and Undifferentiated Carcinoma,
Pathology of the Ovary, Fig. 1 Mesonephric-like
adenocarcinoma. Tubular growth pattern. Colloid-like
eosinophilic material in the lumen
Median age 53 years (range: 21–82 years)
(Silva et al., 2006; Tafe et al., 2010).
• Sex
Female.
• Site
Ovary.
• Clinical Associations/Risk Factors
Nil.
• Treatment
Primary cytoreductive surgery (tot al abdominal hysterectomy and bilateral salpingooophorectomy wi th peritoneal staging) plus
or minus chemotherapy.
• Outcome
These are highly aggressive tumors that tend to
present at an advanced stage and are therefore
associated with a poor prognosis. Median survival time is 9 months (Tafe et al., 2010).
Other Carcinomas and Undifferentiated Carcinoma,
Pathology of the Ovary, Fig. 2 Mesonephric-like ade-
nocarcinoma. Nuclei resembling those of papillary thyroid
carcinoma (clear and overlapping)
Differential Diagnosis
Endometrioid endometrial carcinoma; clear cell
carcinoma; high grade serous carcinoma; mesonephric hyperplasia; carcinosarcoma.
Macroscopy
These are large, solid, extensively necrotic
tumors.
Microscopy
Undifferentiated carcinomas have a diffuse, sheetlike growth pattern with areas of geographical
necrosis. The tumor cells are discohesive, small
to medium sized, with scant cytoplasm and uniform nuclei. Occasionally, they may demonstrate
spindled or rhabdoid morphology. Mitotic activity
is brisk, tumor-infiltrating lymphocytes are a common feature. In dedifferentiated carcinomas, the
Other Carcinomas and Undifferentiated Carcinoma, Pathology of the Ovary 473
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carcinoma (Kuhn et al., 2014;Rosa-Rosa
et al., 2016;Karnezisetal.,2016). There is a
clear association with mismatch repair protein
deficiency/microsatellite instability (two-thirds
of dedifferentiated and one-third of undifferentiated carcinomas are MMR-deficient) (Tafe
et al., 2010; Rosa-Rosa et al., 2016;Karnezis
et al., 2016;Luetal.,2012; Köbel et al., 201 8)
but un-/dedifferentiated carcinomas can a lso
occur in other molecular settings. Inactivating
mutations in SWI/SNF chromatin remodeling
genes ( ARID1A/B and SMARCA4/A2/B1)are
associated with dedifferentiation in approximately two-thirds of dedifferentiated carcinomas and half of undifferentiate d
carcinomas (Karnezis et al., 2016; Köbel et al.,
2018;Strehletal.,2015;Stewart&Crook
2015; Ramalingam et al., 2017;Coatham
et al., 2016).
Other Carcinomas and Undifferentiated Carcinoma,
Pathology of the Ovary, Fig. 3 Dedifferentiated carci-
noma. Differentiated endometrioid carcinoma. Un-/
dedifferentiated component composed of sheets of round,
discohesive cells
Differential Diagnosis
Undifferentiated carcinoma: small cell carcinoma
of the ovary, hypercalcemic type; small cell
neuroendocrine carcinoma; high grade endo-
interface between undifferentiated and differentiated compo nents is often abrupt. The proportion
metrioid stromal sarcoma, lymphoma, and
rhabdomyosarcoma.
of each is variable. The differentiated component
is usually grade 1 or 2 endometrioid carcinoma
but grade 3 endometrioid and serous carcinomas
Carcinosarcoma of the Ovary
have also been reported (Köbel et al., 2010; Tafe
et al., 2010) (Fig. 3).
Definition
Carcinosarcoma is a high grade, biphasic tumor
Immunophenotype
Undifferentiated carcinoma shows focal posi-
composed of malignant epithelial and mesenchymal components.
tivity for EMA, AE1/3, and CK8/18. PAX8
may be focally positive. ER and PR are negative. Neuroendocrine marker s ( synaptophysin
and chromogranin) may be present in a minority
of tumor cells (typically <10%). One-third of
cases show loss of mismatch re pair p rotein
expression (McFarland et al., 2016 ;Porsetal.,
2018).
Clinical Features
• Incidence
Carcinosarcomas account for approximately
2% of all ovarian malignancies (Brown et al.,
2004; Kunkel et al., 2012).
• Age
Tumors typically arise in post-menopausal
women (Brown et al., 2004; Kunkel et al.,
Molecular Features
Clonality studies have demonstrated that the
two components of dedifferentiated carcinoma
are related, the undifferentiated component arising from the accompanying differentiated
2012).
• Sex
Female.
• Site
Ovary.
O
474 Other Carcinomas and Undifferentiated Carcinoma, Pathology of the Ovary
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• Clinical Associations/Risk Factors
Tumors with a high grade serous epithelial
component may exhibit BRCA1 or BRCA 2
mutations.
• Treatment
Primary cytoreductive surgery (tot al abdomi-
nal hysterectomy and bilateral salpingo-
oophorectomy wi th peritoneal staging) plus
or minus chemotherapy.
• Outcome
Patients tend to present with advanced disease
and outcomes are therefore poor. The median
survival is <24 months and the 5-year survival
rate is 15–30% (Brown et al., 2004; Kunkel
et al., 2012; Leiser et al., 2007; Rauh-Hain
et al., 2011). The most important prognostic
Other Carcinomas and Undifferentiated Carcinoma,
Pathology of the Ovary, Fig. 4 Carcinosarcoma.
Biphasic lesion with high grade epithelial and mesenchymal components
factor is the extent to which surgical debulking
is achieved (Brown et al., 2014). The presence
of sarcomatous elements outside of the ovaryis
considered a negative prognostic indicator
(Kunkel et al., 2012).
Macroscopy
These are large (mean size 14 cm), solid/cystic
MBD3, ampl ification of chromosome segments
containing PIK3CA, CCNE1, TERT, and MYC,
an excess of mutations in genes encoding histones
H2A and H2B, and overexpression and mutations
of CDKN1B
, CTNBB1, FBXW7, PPP2R1A,
BCOR, and CHD4 have also been reported
(Cherniack et al., 2017; Jones et al., 2014).
tumors with extensive hemorrhage and necrosis
(Kunkel et al., 2012).
Differential Diagnosis
Dedifferentiated carcinoma; endometrioid carci-
Microscopy
These are biphasic tumors composed of an admixture of high grade carcinoma – typically, though not
exclusively , high grade serous carcinoma (Kunkel
et al., 2012) – and sarcoma. The sarcomatous com-
noma with spindle component; mucinous carcinoma with mural nodules (anaplastic carcinoma
or pseudosarcomatous nodule); poorly differentiated Sertoli-Leydig cell tumor; immature
teratoma.
ponent is referred to as “heterologous” when the
cellular differentiation is apparent from the tumor
morphology and “homologous ” when it is not. The
Mixed Carcinoma of the Ovary
commonest heterolo gous element is rhabdomyosarcoma but chondrosarcoma, osteosarcoma,
liposarcoma, and angiosarcoma may also be seen
(Fig. 4).
Definition
A carcinoma compo sed of two or more histological subtypes that share a common molecular origin Mackenzie et al., 2015).
Immunophenotype
As per the constituent tumor types.
Clinical Features
• Incidence
Molecular Features
These tumors commonly harbor mutations in the
TP53 gene in both the carcinomatous and sarcomatous components (Abeln et al., 1997; Fujii
et al., 2000; Jin et al., 2003). Deletions in
These tumors are rare (<1% of all ovari an
carcinomas).
• Age
The majority of these tumors occur in postmenopausal women.
Other Carcinomas and Undifferentiated Carcinoma, Pathology of the Ovary 475
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• Sex
Female.
• Site
Ovary.
• Clinical Associations/Risk Factors
As for each individual component histotype.
• Treatment
Primary cytoreductive surgery (tot al abdominal hysterectomy and bilateral salpingooophorectomy wi th peritoneal staging) plus
or minus chemotherapy.
• Outcome
Variable, depending on the component
histotypes.
Macroscopy
As for each individual component histotype.
Microscopy
As for each individual component histotype. The
individual tumor types may be present in varying
proportions (there is no minimum percentage
criteria) but they must be morphologically and
immunohistochemically distinct. The commonest
combination is endometrioid and clear cell carcinoma (Mackenzie et al., 2015).
Immunophenotype
As for each individual component histotype.
Molecular Features
As for each individual component histotype.
Mixed endometrioid and clear cell carcinomas
are often mismatch repair protein deficient
(Rambau et al., 2016).
Differential Diagnosis
Ovarian carcinoma of a single histotype with varied morphology, mimicking true mixed
carcinoma.
References and Further Reading
Abeln, E. C., Smit, V. T., Wessels, J. W., de Leeuw, W. J.,
Cornelisse, C. J., & Fleuren, G. J. (1997). Molecular
genetic evidence for the conversion hypothesis of the
origin of malignant mixed Müllerian tumours. The
Journal of Pathology, 183(4), 424–431.
Brown, E., Stewart, M., Rye, T., Al-Nafussi, A., Williams,
A. R., Bradburn, M., Smyth, J., & Gabra, H. (2004).
Carcinosarcoma of the ovary: 19 years of prospective
data from a single center. Cancer, 100(10), 2148–2153.
Cherniack, A. D., Shen, H.,Walter,V., Stewart, C., Murray,
B. A., Bowlby, R., Hu, X., Ling, S., Soslow, R. A.,
Broaddus, R. R., Zuna, R. E., Robertson, G., Laird,
P. W., Kucherlapati, R., Mills, G. B., Cancer Genome
Atlas Research Network, Weinstein, J. N., Zhang, J.,
Akbani, R., & Levine, D. A. (2017). Integrated molecular characterization of uterine carcinosarcoma. Cancer
Cell, 31(3), 411–423.
Coatham, M., Li, X., Karnezis, A. N., Hoang, L. N.,
Tessier-Cloutier, B., Meng, B., Soslow, R. A., Blake
Gilks, C., Huntsman, D. G., Stewart, C. J., Postovit,
L. M., Köbel, M., & Lee, C. H. (2016). Concurrent
ARID1A and ARID1B inactivation in endometrial and
ovarian dedifferentiated carcinomas. Modern Pathol-
ogy, 29(12), 1586–1593.
Fujii, H., Yoshida, M., Gong, Z. X., Matsumoto, T.,
Hamano, Y.,Fukunaga, M., Hruban, R. H., Gabrielson,
E., & Shirai, T. (2000). Frequent genetic heterogeneity
in the clonal evolution of gynecological carcinosarcoma and its influence on phenotypic diversity. Cancer
Research, 60(1), 114–120.
Jin, Z., Ogata, S., Tamura, G., Katayama, Y., Fukase, M.,
Yajima, M., & Motoyama, T. (2003). Carcinosarcomas
(malignant mullerian mixed tumors) of the uterus and
ovary: A genetic study with special reference to histogenesis. International Journal of Gynecological
Pathology, 22(4), 368–373.
Jones, S., Stransky, N., McCord, C. L., Cerami, E.,
Lagowski, J., Kelly, D., Angiuoli, S. V., Sausen, M.,
Kann, L., Shukla, M., Makar, R., Wood, L. D., Diaz,
L. A., Jr., Lengauer, C., & Velculescu, V. E. (2014).
Genomic analyses of gynaecologic carcinosarcomas
reveal frequent mutations in chromatin remodelling
genes. Nature Communications, 5, 5006.
Karnezis, A. N., Hoang, L. N., Coatham, M., Ravn, S.,
Almadani, N., Tessier-Cloutier, B., Irving,J., Meng, B.,
Li, X., Chow, C., McAlpine, J., Kuo, K. T., Mao, T. L.,
Djordjevic, B., Soslow, R. A., Huntsman, D. G., Blake
Gilks, C., Köbel, M., & Lee, C. H. (2016). Loss of
switch/sucrose non-fermenting complex protein
expression is associated with dedifferentiation in endometrial carcinomas. Modern Pathology, 29(3),
302–314.
Köbel, M., Hoang, L. N., Tessier-Cloutier, B., Meng, B.,
Soslow, R. A., Stewart, C. J. R., & Lee, C. H. (2018).
Undifferentiated endometrial carcinomas show frequent loss of core switch/sucrose nonfermentable complex proteins. The American Journal of Surgical
Pathology, 42(1), 76–83.
Köbel, M., Kalloger, S. E., Baker, P. M., Ewanowich,
C. A., Arseneau, J., Zherebitskiy, V., Abdulkarim, S.,
Leung, S., Duggan, M. A., Fontaine, D., Parker, R.,
Huntsman, D. G., & Gilks, C. B. (2010). Diagnosis of
ovarian carcinoma cell type is highly reproducible:
A transcanadian study. The American Journal of Sur-
gical Pathology, 34(7), 984–993.
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476 Other Epithelial Tumors
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Kuhn, E., Ayhan, A., Bahadirli-Talbott, A., Zhao, C., &
IeM, S. (2014). Molecular characterization of
undifferentiated carcinoma associated with endometrioid carcinoma. The American Journal of Surgical
Pathology, 38(5), 660–665.
Kunkel, J., Peng, Y., Tao, Y., Krigman, H., & Cao,
D. (2012). Presence of a sarcomatous component outside the ovary is an adverse prognostic factor for primary ovarian malignant mixed mesodermal/mullerian
tumors: A clinicopathologic study of 47 cases. The
American Journal of Surgical Pathology, 36(6),
831–837.
Leiser, A. L., Chi, D. S., Ishill, N. M.,& Tew, W. P. (2007).
Carcinosarcoma of the ovary treated with platinum and
taxane: The memorial Sloan-Kettering Cancer Center
experience. Gynecologic Oncology, 105(3), 657–661.
Lu, F. I., Gilks, C. B., Mulligan, A. M., Ryan, P., Allo, G.,
Sy, K., Shaw, P. A., Pollett, A., & Clarke, B. A. (2012).
Prevalence of loss of expression of DNA mismatch
repair proteins in primary epithelial ovarian tumors.
International Journal of Gynecological Pathology,
31(6), 524–531.
Mackenzie, R., Talhouk, A., Eshragh, S., Lau, S., Cheung,
D., Chow, C., Le, N., Cook, L. S., Wilkinson, N.,
McDermott, J., Singh, N., Kommoss, F., Pfisterer, J.,
Huntsman, D. G., Köbel, M., Kommoss, S., Gilks,
C. B., & Anglesio, M. S. (2015). Morphologic and
molecular characteristics of mixed epithelial ovarian
cancers. The American Journal of Surgical Pathology,
39(11), 1548–1557.
McFarland, M., Quick, C. M., & McCluggage, W. G.
(2016). Hormone receptor-negative, thyroid transcription factor 1-positive uterine and ovarian adenocarcinomas: Report of a series of mesonephric-like
adenocarcinomas. Histopathology, 68(7), 1013–1020.
Mirkovic, J., Sholl, L. M., Garcia, E., Lindeman, N.,
MacConaill, L., Hirsch, M., Dal Cin, P., Gorman, M.,
Barletta, J. A., Nucci, M. R., McCluggage, W. G., &
Howitt, B. E. (2015). Targeted genomic profiling
reveals recurrent KRAS mutations and gain of chromosome 1q in mesonephric carcinomas of the female
genital tract. Modern Pathology, 28(11), 1504–1514.
Pors, J., Cheng, A., Leo,J. M., Kinloch, M.A., Gilks, B., &
Hoang, L. (2018). A comparison of GATA3, TTF1,
CD10, and Calretinin in identifying mesonephric and
mesonephric-like carcinomas of the gynecologic tract.
The American Journal of Surgical Pathology, 42(12),
1596–1606.
Ramalingam, P., Croce, S., & McCluggage, W. G. (2017).
Loss of expression of SMARCA4 (BRG1),
SMARCA2 (BRM) and SMARCB1 (INI1) in
undifferentiated carcinoma of the endometrium is not
uncommon and is not always associated with rhabdoid
morphology. Histopathology, 70(3), 359–366.
Rambau, P. F., Duggan, M. A., Ghatage, P., Warfa, K.,
Steed, H., Perrier, R., Kelemen, L. E., & Köbel,
M. (2016). Significant frequency of MSH2/MSH6
abnormality in ovarian endometrioid carcinoma supports histotype-specific Lynch syndrome screening in
ovarian carcinomas. Histopathology, 69(2), 288–297.
Rauh-Hain, J. A., Growdon, W. B., Rodriguez, N., Good-
man, A. K., Boruta, D. M., 2nd, Schorge, J. O., Horowitz, N. S., & del Carmen, M. G. (2011).
Carcinosarcoma of the ovary: A case-control study.
Gynecologic Oncology, 121(3), 477–481.
Rosa-Rosa, J. M., Leskelä, S., Cristóbal-Lana, E., Santón,
A., López-García, M. Á., Muñoz, G., Pérez-Mies, B.,
Biscuola, M., Prat, J., Esther, O., Soslow, R. A.,MatiasGuiu, X., & Palacios, J. (2016). Molecular genetic
heterogeneity in undifferentiated endometrial carcinomas. Modern Pathology, 29(11), 1390–1398.
Silva, E. G., Deavers, M. T., Bodurka, D. C., & Malpica,
A. (2006). Association of low-grade endometrioid carcinoma of the uterus and ovary with undifferentiated
carcinoma: A new type of dedifferentiated carcinoma?
International Journal of Gynecological Pathology,
25(1), 52–58.
Stewart, C. J., & Crook, M. L. (2015). SWI/SNF complex
deficiency and mismatch repair protein expression in
undifferentiated and dedifferentiated endometrial carcinoma. Pathology, 47(5), 439–445.
Strehl, J. D., Wachter, D. L., Fiedler, J., Heimerl, E.,
Beckmann, M. W., Hartmann, A., & Agaimy,
A. (2015). Pattern of SMARCB1 (INI1) and
SMARCA4 (BRG1) in poorly differentiated endometrioid adenocarcinoma of the uterus: Analysis of a
series with emphasis on a novel SMARCA4-deficient
dedifferentiated rhabdoid variant. Annals of Diagnostic
Pathology, 19(4), 198–202.
Tafe, L. J., Garg, K., Chew, I., Tornos, C., & Soslow, R. A.
(2010). Endometrial and ovarian carcinomas with
undifferentiated components: Clinically aggressive
and frequently underrecognized neoplasms. Modern
Pathology, 23(6), 781–789.
Other Epithelial Tumors
(Adenosquamous Carcinoma,
Mucoepidermoid Carcinoma,
Adenoid Basal Carcinoma,
Adenoid Cystic Carcinoma),
Pathology of the Cervix
Lynn Hoang
Anatomical Pathology, Vancouver General
Hospital, Vancouver, BC, Canada
University of British Columbia, Vancouver, BC,
Canada
Adenosquamous Carcinoma
Synonyms
Glassy cell carcinoma.
Other Epithelial Tumors 477
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Definition
A tumor of the cervix comp rising of unequivocal malignant glandular and squamous
differentiation.
Clinical Features
• Incidence
The frequency has varied widely in the literature, from 2% to 50%, due to varied definitions. Many adenosquamous carcinomas have
been reclassified as pure invasive stratified
mucin-producing carcinomas (ISMC), mixed
ISMC with other components, HPV-associated
usual-type adenocarcinoma, and HPVassociated mucinous adenocarcinoma.
• Age
Other Epithelial Tumors (Adenosquamous Carcinoma, Mucoepidermoid Carcinoma, Adenoid Basal
Carcinoma, Adenoid Cystic Carcinoma), Pathology of
the Cervix, Fig. 1 Adenosquamous carcinoma. This field
shows the adenocarcinoma component
The mean patient age is 46 years (range:
24–68 years).
• Sex
Female.
• Site
Uterine cervix.
• Treatment
Surgical resection with consideration of lymph
node dissection and adjuvant therapy.
• Outcome
Two-thirds present with FIGO stage I disease
and one-third will have metastases to lymph
nodes at presentation. In the older literature,
adenosquamous carcinomas were reported to
occur in younger patients, pregnant patients
and had a worse prognosis than squamous
Other Epithelial Tumors (Adenosquamous Carcinoma, Mucoepidermoid Carcinoma, Adenoid Basal
Carcinoma, Adenoid Cystic Carcinoma), Pathology of
the Cervix, Fig. 2 Adenosquamous carcinoma. This is the
same case as Fig. 1.Thisfield shows the adjacent squamous
cell carcinoma component
cell carcinomas and adenocarcinomas. In a
recent study, the overall survival and diseasefree survival were no different than in HPVassociated adenocarcinoma and ISMC, and
there was no association with pregnancy
(Stolnicu et al. 2019).
thirds show lym phovascula r invasion. They
can have a micropapillary pattern, where the
papillae show inside-out (reverse polarity)
staining with MUC1 (Stewart et al. 2018). Half
are associated with an in-situ lesion such as
Macroscopy
Exophytic or indurated mass of the uterine cervix.
high-grade squamous intraepithelial lesion
(HSIL), adenocarcinoma in situ (AIS), or stratified mucin-producing intraepithelial lesion
Microscopy
Adenosquamous carcinomas exh ibit unequivocal adenocarcinoma and squamous cell carcinoma components (Figs. 1 and 2). This should
be apparent histologically, without the need for
special stains. Half are high-grade and two-
(LSIL).
Glassy cell carcinoma is made of solid nests of
polygonal tumor cells with prominent cell borders, glassy eosinophilic cytoplasm, large eosinophilic nuclei, and prominent nucleoli. The cells
are surrounded by a dense inflammatory infiltrate
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478 Other Epithelial Tumors
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containing eosinophils. Glassy cell carcinoma is
considered a variant of adenosquamou s carcinoma. Some cases of glassy cell carcinoma have
more recently been defined as HPV-associated
usual-type, poorly differentiated, due to p40 and
p63 negativity (Stolnicu et al. 2019).
Immunophenotype
The majority of adenosquamous carcinomas are
associated with HPV infection. p16 shows
block-like positivity in 72% of cases and HPV
RNA in-situ hybridization in 83% of cases. In
comparison to ISMC, they are more likely to
show PAX8 (43% vs. 29%), p40 (65%
vs. 29%), p63 (60% vs. 38%) positivity and
less likely to show MUC6 (22% vs. 57%),
vimentin (0% vs. 13%), and CK7 (87%
vs. 100%) (Stolnicu et al. 2019).
Molecular Features
Do not show activating mutations in EGFR or
PDGFRA (Longatto-Filho et al. 2009).
Differential Diagnosis
ISMC will also have glandular and squamo us
differentiation but in a more blended rather
than discrete pattern. p63 and p40 is more common in ade nosquamous carcinoma. In ISMC,
p63 will be accentuated at the periphery of the
nests.
Mucoepidermoid carcinoma (MEC) will have
three different cell types: epidermoid/squamous
cells, mucous cells, and intermediate cells. It
lacks overt glandular differentiation, unlike in
adenosquamous carcinoma where a distinct adenocarcinoma component will be present. MEC
also does not present with an HPV-associated
precursor lesion.
HPV-associated usual-type adenocarcinomas
can be associated with a bland/reactive squamous proliferation, which should not be mistaken for adenosquamous carcinoma (Stolnicu
et al. 2019).
Endometrioid carcinoma with squamous differentiation extending into the cervix from the
uterine corpus should be excluded. These tumors
will be negative/patchy staining for p16 and be
positive for ER and vimentin.
Mucoepidermoid Carcinoma
Definition
A malignant epithelial tumor exhibiting both
squamous and glandular differentiation.
Clinical Features
• Incidence
This is a rare tumor. In one institutional study, a
review of the 10-year period showed that
mucoepidermoid carcinomas comprised
1.12% of all stage I cervical cancers
(Yordanov et al. 2020).
• Age
The mean age is 47–51 years (range:
34–72 years).
• Sex
Female.
• Site
Most occur at the squamocolumnar junction.
• Treatment
Due to the risk of lymph node metastases,
complete excision and lymph node sampling
are recommended. Adjuvant therapy has been
used in the literature.
• Outcome
Approximately one-third of patients will have
lymph node metastases. In one study, the rate
of lymph node metastases was higher in
mucoepidermoid carcinomacompared to squamous cell carcinoma (33 vs. 14%) (Thelmo
et al. 1990). The 5-year overall survival was
85.7% in one study, which was slightly better
than in the adenosquamous carcinoma group
(71.4%) (Yordanov et al. 2020).
Macroscopy
Half of patients will have a mass lesion in the
cervix.
Microscopy
Mucoepidermoid carcinoma demonstrates histologic features similar to that seen in the salivary
gland. They comprise of three cell types: (1) epidermoid/squamoid cells, (2) mucous cells, and
(3) intermediate cells. The intermediate cells
range from small basaloid cells to large round
cells with more abundant eosinophilic cytoplasm.
Other Epithelial Tumors 479
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The intermediate cells tend to blend with the two
other cell types. Distinct glands are not present.
Immunophenotype
Few studies have performed an extensive immunohistochemical panel. The tumors are positive for
pankeratin, CEA, and EMA. The mucin will stain
positive for PASD and Alcian blue (Thelmo
et al. 1990).
Molecular Features
A single study has shown CRTC1-MAML2 fusion,
rearrangements of CRTC1, and aberrations of
MAML2 in mucoepidermoid carcinoma of the
cervix (Lennerz et al. 2009).
Differential Diagnosis
The appearance can be difficult to distinguish from
invasive stratified mucin-producing carcinoma
(ISMC). ISMC will be associated with various
HPV-associated precursor lesions (stratified
mucin-producing intraepithelial lesions, adenocarcinomain situ, high-grade squamousintraepithelial
lesions), intralesional neutrophilic infiltrates, and
conspicuous apoptotic debris.
Adenosquamous carcinoma also has glandular
and squamous components; however, there will
be a distinct glandular component.
Adenoid Basal Carcinoma
Synonyms
Adenoid basal epithelioma; Low-grade adenoid
basal tumor.
Definition
An epithelial tumor comprising of small rounded
nests of morphologically bland basaloid cells.
Clinical Features
• Incidence
These are rare tumors that constitute <1% of
all cervical cancers. Some studies suggest a
higher incidence in women of African descent.
• Age
A wide age range has been reported
(20–90 years of age).
• Sex
Female.
• Site
Uterine cervix.
• Treatment
In general, due to their indolent clinical behavior, these tumors require only conservative
treatment. Complete excision is recommended
to rule out an admixed high-grade tumor, such
as squamous cell carcinoma.
• Outcome
These tumors are indolent, with no propensity
for metastases or patient deaths, when pure
adenoid basal carcinoma is present. Due to
their rather banal clinical behavior, some
authors prefer to use the term adenoid basal
epithelioma (Brainard and Hart 1998).
Macroscopy
These tumors are not usually seen macroscopically. They are usually detected upon further
workup for an abnormal PAP smear showing
high-grade squamous intraepithelial lesion.
Microscopy
Almost all of these tumors are found adjacent to
high-grade squamous intraepithelial lesion and
are associated with high-risk human p apillomavirus infection.
They are made of morphologically bland
basaloid cells, which form widely spaced nests
or cords. Periphera l palisading, cystic cha nges,
clear cell changes, and focal glandular or squamous differentiation can be seen (Figs. 3, 4,and
5). When the nests become cystically dilated,
the basaloid cells can be more difficult to appreciate. The inner aspects of the nests can be lined
by mucinous epithelium or filled with
squamous/transitional-like cells. The squamous
cells usually show mild atypia, but high-grade
dysplasia can be seen (Fig. 6). Stromal
desmoplasia is not common. Mitotic activity is
generally low.
Although most adenoid cystic carcinomas
exist in pure form, occasionally they can be
admixed with squamous cell carcinoma,
adenosquamous carcinoma, adenoid cystic carcinoma, small cell neuroendocrine carcinoma, and
O
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