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Mesenchymal Tumors and Mixed Epithelial and Mesenchymal Tumors, Pathology of the Vulva 219
https://t.me/med1917
Molecular Features
A subset of superficial angiomyxoma occur as
part of the Carney complex, which is caused by
germline mutations in the PRKAR1A gene in a
majority of patients (Kirschner et al. 2000).
Differential Diagnosis
Tumors that occur as part of the Carney complex
are identical to those occurring sporadically.
Superficial angiomyxoma may be the first presentation of this autosomal dominant disorder, and
the clinician should be alerted to the possibility of
the patient being affected, particularly if the
Mesenchymal Tumors and Mixed Epithelial and Mesenchymal Tumors, Pathology of the Vulva,
Fig. 43 Superficial angiomyxoma – microscopic features.
Tumor cells are spindled and cytologically bland with
delicate cytoplasmic processes. Mitoses may be seen
patient has external ear lesions or multiple lesions.
Superficial angiomyxoma must be distinguished
from aggressive angiomyxoma, which is typically
deeper seated, irregularly shaped with a more
nodular growth pattern, and has a tendency for
local recurrence. Additionally, aggressive
angiomyxoma is characterized by the presence
of thick-walled vessels, which are not commonly
seen in superficial angiomyxoma. Additionally,
aggressive angiomyxomas lack epithelial proliferations that are not uncommonly seen in superficial angiomyxoma. Myxofibrosarcoma shows
cytologic atypia and contains prominent “curvilinear” blood vessels. Myxoid neurofibroma and
nerve sheath myxoma express S100 protein and
SOX-10. Myxoid leiomyosarcoma and aggressive
angiomyxoma express smooth muscle markers
such as smooth muscle actin and desmin.
M
Mesenchymal Tumors and Mixed Epithelial and Mesenchymal Tumors, Pathology of the Vulva,
Fig. 44 Superficial angiomyxoma – microscopic features.
Superficial angiomyxomas are often associated with epithelial proliferations, most commonly cysts. Abnormal hair
follicles may also be present
angiomyxoma (Fig. 44). Abnormal hair follicles
may also be encountered.
Immunophenotype
Immunohistochemistry does not play a significant
role in the diagnosis of superficial angiomyxoma.
Tumors are negative for nerve sheath markers
such as S100 protein and SOX-10 and are negative for smooth muscle markers such as smooth
muscle actin and desmin.
References and Further Reading
Agaram, N. P., Leloarer, F. V., Zhang, L., Hwang, S.,
Athanasian, E. A., Hameed, M., & Antonescu, C. R.
(2014). USP6 gene rearrangements occur preferentially
in giant cell reparative granulomas of the hands and feet
but not in gnathic location. Human Pathology, 45(6),
1147–1152. https://doi.org/10.1016/j.humpath.2014.
01.020.
Amezcua, C. A., Begley, S. J., Mata, N., Felix, J. C., &
Ballard, C. A. (2005). Aggressive angiomyxoma of the
female genital tract: A clinicopathologic and immuno-
histochemical study of 12 cases. International Journal
of Gynecological Cancer, 15(1), 140–145. https://doi.
org/10.1111/j.1048-891x.2005.15015.x.
Billings, S. D., Patel, R. M., & Buehler, D. (Eds.). (2019).
Soft tissue tumors of the skin (1st ed.). New York:
Springer Nature.
220 Mesenchymal Tumors and Mixed Epithelial and Mesenchymal Tumors, Pathology of the Vulva
https://t.me/med1917
Blandamura, S., Cruz, J., Faure Vergara, L., Machado
Puerto, I., & Ninfo, V. (2003). Aggressive
angiomyxoma: A second case of metastasis with
patient’sdeath.Human Pathology, 34(10), 1072–1074.
https://doi.org/10.1053/S0046-8177(03)00419-2.
Calonje, E., Guerin, D., McCormick, D., & Fletcher,
C. D. M. (1999). Superficial angiomyxoma: Clinicopathologic analysis of a series of distinctive but poorly
recognized cutaneous tumors with tendency for recurrence. American Journal of Surgical Pathology, 23(8),
910– 917. https://doi.org/10.1097/00000478-
199908000-00008.
Carney, J. A., Hruska, L. S., Beauchamp, G. D., & Gordon,
H. (1986). Dominant inheritance of the complex of
myxomas, spotty pigmentation, and endocrine overactivity. Mayo Clinic Proceedings, 61(3), 165–172.
https://doi.org/10.1016/S0025-6196(12)61843-6.
Carter, J. M., Wang, X., Dong, J., Westendorf, J., Chou,
M. M., & Oliveira, A. M. (2016). USP6 genetic
rearrangements in cellular fibroma of tendon sheath.
Modern Pathology, 29(8), 865–869. https://doi.org/
10.1038/modpathol.2016.83.
Chan, I. M., Hon, E., Ngai, S. W., Ng, T. Y., & Wong, L. C.
(2000). Aggressive angiomyxoma in females: Is radical
resection the only option? Acta Obstetricia et
Gynecologica Scandinavica, 79(3), 216–220. https://
doi.org/10.1034/j.1600-0412.2000.079003216.x.
Chen, B. J., Mariño-Enríquez, A., Fletcher, C. D. M., &
Hornick, J. L. (2012). Loss of retinoblastoma protein
expression in spindle cell/pleomorphic lipomas and
cytogenetically related tumors: An immunohistochemical study with diagnostic implications. American Jour-
nal of Surgical Pathology, 36(8), 1119–1128. https://
doi.org/10.1097/PAS.0b013e31825d532d.
Crum, C. P., Nucci, M. R., Howitt, B. E., Granter, S. R.,
Parast, M. M., & Boyd, T. K. (Eds.). (2018). Diagnostic
gynecologic and obstetric pathology(3rd ed.). Elsevier.
Doyle, L. A., Vivero, M., Fletcher, C. D. M., Mertens, F., &
Hornick, J. L. (2014). Nuclear expression of STAT6
distinguishes solitary fibrous tumor from histologic
mimics. Modern Pathology, 27(3), 390–395. https://
doi.org/10.1038/modpathol.2013.164.
Fanburg-Smith, J. C., Meis-Kindblom, J. M., Fante, R., &
Kindblom, L.-G. (1998). Malignant granular cell tumor
of soft tissue: Diagnostic criteria and clinicopathologic
correlation. American Journal of Surgical Pathology,
22(7), 779–794.
Ferreiro, J. A., & Carney, J. (1994). Myxomas of the
external ear and their significance. The American Jour-
nal of Surgical Pathology, 18(3), 274–
Fetsch, J. F., Laskin, W. B., Lefkowitz, M., Kindblom,
L.-G., & Meis-Kindblom, J. M. (1996). Aggressive
angiomyxoma: A clinicopathologic study of
29 female patients. Cancer, 78(1), 79–90.
Fetsch, J. F., Laskin, W. B., & Tavassoli, F. A. (1997).
Superficial angiomyxoma (cutaneous myxoma):
A clinicopathologic study of 17 cases arising in the
genital region. International Journal of Gynecological
Pathology, 16(4), 325–334.
280.
Fletcher, C. D., Tsang, W. Y., Fisher, C., Lee, K. C., &
Chan, J. K. (1992). Angiomyofibroblastoma of the
vulva. The American Journal of Surgical Pathology,
16, 373–382. https://doi.org/10.2336/nishinihonhifu.
61.481.
França, J. A., de Sousa, S. F., Moreira, R. G., Bernardes,
V. F., Guimarães, L. M., Santos, J. N., ...Gomes, C. C.
(2018). Sporadic granular cell tumours lack recurrent
mutations in PTPN11, PTEN and other cancer-related
genes. Journal of Clinical Pathology, 71(1), 93–94.
https://doi.org/10.1136/jclinpath-2017-204849.
Goodlad, J. R., & Fletcher, C. D. M. (1990). Intradermal
variant of nodular ‘fasciitis’. Histopathology, 17(6),
569–571. https://doi.org/10.1111/j.1365-2559.1990.
tb00799.x.
Granter, S. R., Nucci, M. R., & Fletcher, C. D. M. (1997).
Aggressive angiomyxoma: Reappraisal of its relation-
ship to angiomyofibroblastoma in a series of 16 cases.
Histopathology, 30(1), 3–10. https://doi.org/10.1046/j.
1365-2559.1997.d01-556.x.
Horowitz, I., Copas, P., & Majmudar, B. (1995). Granular
cell tumors of the vulva. American Journal of Obstet-
rics and Gynecology, 173(6); discussion 1713– 1714.
https://doi .org/10.5631/jibirinsuppl1986.2002.supple-
ment109_81.
Iezzoni, J. C., Fechner, R. E., Wong, L. S., & Rosai,
J. (1995). Aggressive angiomyxoma in males:
A report of four cases. American Journal of Clinical
Pathology, 104(4), 391–396.
Iwasa, Y., & Fletcher, C. D. M. (2004). Cellular
angiofibroma: Clinicopathologic and immunohisto-
chemical analysis of 51 cases. The American Journal
of Surgical Pathology, 28(11), 1426–1435. https://doi.
org/10.1097/01.pas.0000138002.46650.95.
Kirschner, L. S., Carney, J. A., Pack, S. D., Taymans, S. E.,
Giatzakis, C., Cho, Y. S., Cho-Chung, Y. S., &
Stratakis, C. A. (2000). Mutations of the gene encoding
the protein kinase a type I-α regulatory subunit
(PRKAR1A) in patients with the “complex of spotty
skin pigmentation, myxomas, endocrine overactivity,
and schwannomas” (Carney complex). Nature Genet-
ics, 26(1), 89–92. https://doi.org/10.1111/j.1749-6632.
2002.tb04323.x.
Lack, E. E., Worsham, G. F., Callihan, M. D., Crawford,
B. E., Klappenbach, S., Rowden, G., & Chun,
B. (1980). Granular cell tumor: A clinicopathologic
study of 110 patients. Journal of Surgical Oncology,
13(4), 301–316.
Laskin, W. B., Fetsch, J. F., & Tavassoli, F. A. (1997).
Angiomyofibroblastoma of the female genital tract:
Analysis of 17 cases including a lipomatous variant.
Human Pathology, 28(9), 1046–1055. https://doi.org/
10.1016/S0046-8177(97)90058-7.
Laskin, W. B., Fetsch, J. F., & Mostofi, F. K. (1998).
Angiomyofibroblastomalike tumor of the male genital
tract: Analysis of 11 cases with comparison to female
angiomyofibroblastoma and spindle cell lipoma. Amer-
ican Journal of Surgical Pathology, 22(1), 6–16.
https://doi.org/10.1097/00000478-199801000-00002.
Mesenchymal Tumors and Mixed Epithelial and Mesenchymal Tumors, Pathology of the Vulva 221
https://t.me/med1917
Luis, P. P., Quiñonez, E., Nogales, F. F., & McCluggage,
W. G. (2015). Lipomatous variant of angiomyofibroblastoma involving the vulva: Report of 3 cases of an
extremely rare neoplasm with discussion of the differential diagnosis. International Journal of Gynecologi-
cal Pathology, 34(2), 204–207. https://doi.org/10.
1097/PGP.0000000000000131.
Machado, I., Cruz, J., Lavernia, J., & Llombart-Bosch,
A. (2016). Solitary, multiple, benign, atypical, or
malignant: The “granular cell tumor” puzzle. Virchows
Archiv, 468(5), 527–538. https://doi.o rg/10.1007/
s00428-015-1877-6.
Magro, G., Righi, A., Caltabiano, R., Casorzo, L., &
Michal, M. (2014). Vulvovaginal angiomyofibroblastomas: Morphologic, immunohistochemical, and
fluorescence in situ hybridization analysis for deletion
of 13q14 region. Human Pathology, 45(8), 1647–1655.
https://doi.org/10.1016/j.humpath.2014.03.020.
Marchese, C., Montera, M., Torrini, M., Forni, M., Gol-
doni, F., Locatelli, L., & Mareni, C. (2003). Granular
cell tumor in a PHTS patient with a novel
germlinePTEN mutation. American Journal of Medical
Genetics, 120A(2), 286–288. https://doi.org/10.1002/
ajmg.a.20179.
McCluggage, W. G., Connolly, L., & McBride, H. A.
(2010). HMGA2 is a sensitive but not specific immunohistochemical marker of vulvovaginal aggressive
angiomyxoma. American Journal of Surgical Pathol-
ogy, 34(7), 1037–1042. https://doi.org/10.1097/PAS.
0b013e3181e32a11.
Medeiros, F., Erickson-Johnson, M. R., Keeney, G. L.,
Clayton, A. C., Nascimento, A. G., Wang, X., &
Oliveira, A. M. (2007). Frequency and characterization
of HMGA2 and HMGA1 rearrangements in mesenchymal tumors of the lower genital tract. Genes, Chromo-
somes & Cancer, 46(11), 981–990. https://doi.org/10.
1002/gcc.20483.
Nielsen, G. P., Rosenberg, A. E., Young, R. H., Dickersin,
G. R., Clement, P. B., & Scully, R. E. (1996).
Angiomyofibroblastoma of the vulva and vagina. Mod-
ern Pathology, 9(3), 284–291.
Nucci, M. R., Granter, S. R., & Fletcher, C. D. M. (1997).
Cellular angiofibroma: A benign neoplasm distinct
from angiomyofibroblastoma and spindle cell lipoma.
American Journal of Surgical Pathology, 21(6),
636– 644. https://doi.org/10.1097/00000478-
199706000-00002
Nucci, M. R., Young, R. H., & Fletcher, C. D. M. (2000).
Cellular pseudosarcomatous fibroepithelial stromal
polyps of the lower female genital tract: An
underrecognized lesion often misdiagnosed as sarcoma. American Journal of Surgical Pathology,
24(2), 231–240. https://doi.org/10.1097/00000478-
200002000-00009.
O’Connell, J. X., Young, R. H., Nielsen, G. P., Rosenberg,
A. E., Bainbridge, T. C., & Clement, P. B. (1997).
Nodular fasciitis of the vulva: A study of six cases
and literature review. International Journal of Gyneco-
logical Pathology, 16(2), 117–123.
.
O’Quinn, A. G., Edwards, C. L., & Gallager, H. S. (1982).
Pseudosarcoma botryoides of the vagina in pregnancy.
Gynecologic Oncology, 13(2), 237– 241. https://doi.
org/10.1016/0090-8258(82)90032-4.
Oliveira, A. M., & Chou, M. M. (2014). USP6-induced
neoplasms: The biologic spectrum of aneurysmal bone
cyst and nodular fasciitis. Human Pathology, 45(1),
1–11. https://doi.org/10.1016/j.humpath.2013.03.005.
Oliveira, Andre M, Hsi, B., Weremowicz, S., Rosenberg,
A. E., Cin, P. D., Joseph, N., ...Fletcher, J. A. (2004).
USP6 (Tre2) fusion oncogenes in aneurysmal bone cyst
USP6 (Tre2) fusion oncogenes in aneurysmal bone
cyst. Cancer Research, 64(6), 1920–1923.
Pérez-González, Y. C., Pagura, L., Llamas-Velasco, M.,
Cortes-Lambea, L., Kutzner, H., & Requena, L. (2015).
Primary cutaneous malignant granular cell tumor: An
immunohistochemical study and review of the literature.
American Journal of Dermatopathology, 37(4), 334–340.
https://doi.org/10.1186/s13000-015-0357-2 .
Pichler Sekulic, S., & Sekulic, M. (2016). Nodular fasciitis
of the vulva: A challenging histopathologic diagnosis
supported by the detection of USP6 gene
rearrangement. APMIS, 124(6), 534–537. https://doi.
org/10.1111/apm.12532.
Rabban, J. T., Dal Cin, P., & Oliva, E. (2006). HMGA2
rearrangement in a case of vulvar aggressive
angiomyxoma. International Journal of Gynecological
Pathology, 25(4), 403–407. https://doi.org/10.1097/01.
pgp.0000209572.54457.7b.
Ramaswamy, P., Storm, C., Filiano, J., & Dinulos, J. (2010).
Multiple granular cell tumors in a child with Noonan
syndrome. Pediatric Dermatology, 27(2), 209–211.
https://doi.org/10.1055/s-0032-1322537.
Schmidt, O., Fleckenstein, G. H., Gunawan, B., Füzesi, L.,
& Emons, G. (2003). Recurrence and rapid metastasis
formation of a granular cell tumor of the vulva.
European Journal of Obstetrics and Gynecology and
Reproductive Biology, 106(2), 219–221. https://doi.
org/10.1016/S0301-2115(02)00165-3.
Schoolmeester, J. K., & Fritchie, K. J. (2015). Genital soft
tissue tumors. Journal of Cutaneous Pathology, 42(7),
441–451. https://doi.org/10.1111/cup.12507.
Schrader, K. A., Nelson, T. N., De Luca, A., Huntsman,
D. G., & Mcgillivray, B. C. (2009). Multiple granular
cell tumors are an associated feature of LEOPARD syn-
drome caused by mutation in PTPN11. Clinical Genetics,
75(2), 185–189. https://doi.org/10.1111/j.1399-0004.
2008.01100.x.
Shimokama, T., & Watanabe, T. (1992). Leiomyoma
exhibiting a marked granular cell change: Granular
cell leiomyoma versus granular cell schwannoma.
Human Pathology, 23(3), 327–331.
Steeper, T. A., & Rosai, J. (1983). Aggressiveangiomyxoma
of the female pelvis and perineum. Report of nine cases
of a distinctivetype of gynecologicsoft-tissueneoplasm.
American Journal of Surgical Pathology, 7(5), 463–475.
https://doi.org/10.1097/00000478-198307000-00009.
Sutton, B. J., & Laudadio, J. (2012). Aggressive
angiomyxoma. Archives of Pathology and Laboratory
M
222 Mesenchymal Tumors, Pathology of the Ovary
https://t.me/med1917
Medicine, 136(2), 217–221. https://doi.org/10.5858/
arpa.2011-0056-RS.
Van Roggen, J. F. G., Van Unnik, J. A. M., Briaire-De
Bruijn, I. H., & Hogendoorn, P. C. W. (2005). Aggressive angiomyxoma: A clinicopathological and immunohistochemical study of 11 cases with long-term
follow-up. Virchows Archiv, 446(2), 157–163. https://
doi.org/10.1007/s00428-004-1135-9.
Weaver, J., Goldblum, J. R., Turner, S., Tubbs, R. R.,
Wang, W. L., Lazar, A. J. F., & Rubin, B. P. (2009).
Detection of MDM2 gene amplification or protein
expression distinguishes sclerosing mesenteritis and
retroperitoneal fibrosis from inflammatory welldifferentiated liposarcoma. Modern Pathology, 22(1),
66–70. https://doi.org/10.1038/modpathol.2008.153.
Wolber, R. A., Talerman, A., Wilkinson, E. J., & Clement,
P. B. (1991). Vulvar granular cell tumors with pseudocarcinomatous hyperplasia: A comparative analysis
with well-differentiated squamous carcinoma. Interna-
tional Journal of Gynecological Pathology, 10(1),
59–66.
Mesenchymal Tumors,
Pathology of the Ovary
Ghassan Allo
Department of Pathology and Laboratory
Medicine, Henry Ford Health, Detroit, MI, USA
Endometrioid Stromal Sarcoma of
the Ovary
Synonyms
Extrauterine endometrial stromal sarcoma of
ovary; Low-grade endometrioid stromal sarcoma
of ovary.
Definition
Endometrioid stromal sarcoma is a mesenchymal
tumor of the ovary, demonstrating evidence of
endometrial-type stromal differentiation in the
absence of uterine origin.
Clinical Features
• Incidence
These tumors are rare.
• Age
Ovarian endometrioid stromal sarcomas can
occur at a wide age range, being reported in
women as young as 20 years of age and as old
as 87. The majority are diagnosed in perimen-
opausal and early postmenopausal period at
mean age of diagnosis of 50 years.
• Symptoms
Patients with ovarian endometrioid stromal
sarcoma usually present with nonspecific
symptoms similar to those of other ovari an
tumors. These include abdominal swelling,
abdominal pain, and bowel obstruction. They
can also be diagnosed incidentally by imaging
for unrelated conditions or complaints.
• Treatment
The mainstay of treatment for these tumors is a
cytoreductive surgical excision. This includes
hysterectomy to rule out the uterine origin of
the sarcoma and pelvic and abdominal surveil-
lance to exclude other extrauterine tissue
involvement, a phenomenon commonly asso-
ciated with ovarian endometrioid stromal sar-
coma. Adjuvant hormonal therapy may be
offered. Chemoradiation can be considered in
recurrent cases.
• Outcome
There is limited data on the behavior of endo-
metrial stromal sarcomas of the ovary
because of their rarity. In addition, there are
inconsistent outcome results, as some studies
combined these tumors with other extrauter-
ine endometrial stromal sarcomas. Earlier
studies described a more aggressive outcome
comparable to hig h-stage uterine endome-
trial stromal sarcomas with recurrence rate
of 77% and disease-specific mortality rate
of 38% at average follow-up of 65 months
(Chang et al. 1993). More recent reports
describe an outcome better than other ovar-
ian sarcomas and more resembling that of
low-stage uterine endometrial stromal sarco-
mas with recurrence rate of 62% and disease-
specific mortality rates of 17–24% (Masand
et al. 2013; Oliva et al. 2014). The presence
of high- grade cytology (“dedifferentiation” )
is the only indication of potential worse out-
come, while no other histologic features like
mitotic activity, necrosis, tumor size, loca-
tion, or vascular invasion are prognostically
significant.
Mesenchymal Tumors, Pathology of the Ovary 223
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Macroscopy
Endometrioid stromal sarcomas can be confined
to the ovaries but not infrequently involve other
pelvic or abdominal sites (“extrauterine endometrial stromal sarcoma”). Within the ovaries, they
can be unilateral or bilateral, presenting as solid
or cystic, tan or yellow-white masses, ranging
from 1 to more than 20 cm in maximum dimension. Areas of hemorrhage or necrosis may be
present.
Microscopy
The tumor shows histologic features resembling
those of proliferative type endometrial stroma. It
is composed of closely packed oval to round
tumor cells growing in sheets and sometimes
vague nodules with thick-walled arteriolar proliferations resembling spiral arteries (Fig. 1a, b).
Background endometriosis is found in more than
50% of cases. These tumors generally lack the
classical tongue-like invasion and vascular
involvement that is seen in uterine endometrial
stromal sarcomas or other extraovarian endometrioid sarcoma. The tumor cells are m onomorphic, containing low to moderate amount of pale
to eosinophilic cytoplasm and round to oval
nuclei with homogenous chromatin and variably
distinct nucleoli. The tumor mitotic activity can
be variable, ranging from 0 to 28 mitoses per
10 high-power fields without correlation with
prognosis. In addition, necrosis, especially ischemic, can be seen and once again does not correlate with prognosis. Areas of marked diffuse
cytologic pleomorphism with increased mitotic
activity and loss of the typical vascular patt ern
(“dedifferentiation”) can be uncommonly seen.
These areas of dedifferentiation are suggested to
be associated with shorter s urvival, higher recurrence, and resistance to adjuvant chemotherapy
and radiation therapy (Masand et al. 2013;Oliva
et al. 2014).
In addition to the classical endometrioid stromal morphology, the tumor may exhibit fibromatous differentiation (short intersecting
bundles of spindled cells embedded in collagenous stroma with hyaline plaques), sex cord
growth pattern (small cords, trabeculae, and epithelioid islands with peripheral nuclear palisading), and smooth muscle differentiation (Oliva
et al. 2014).
Immunophenotype
Like other sarcomas with endometrioid stromal
differentiation, ovarian endometrioid stromal sarcomas are diffusely positive for estrogen and progesterone receptors and CD10, and focally
positive for smooth muscle actin (SMA) and
desmin. Areas with sex cord growth can express
inhibin and calretinin. The high-grade
“dedifferentiated” areas only focally express ER,
PR, and CD10, while cyclin D1 is reportedly
diffusely positive (Xie et al. 2017).
Molecular Features
The data on the molecular background of ovarian
endometrioid stromal sarcoma are limited by the
number of tested cases and the limited range of the
investigated genes. These limited reports suggest
that many of ovarian endometrioid stromal sarcomas carried JAZF1-JJAZ1 fusion, and less
M
Mesenchymal Tumors, Pathology of the Ovary, Fig. 1 Endometrioid stromal sarcoma showing sheets and vague
nodular proliferations of monomorphic oval to round spindle cells with associated arteriolar proliferations
224 Mesenchymal Tumors, Pathology of the Ovary
https://t.me/med1917
commonly JAZF1-PHF1 and EPC1-PHF1 gene
fusions (Amador-Ortiz et al. 2011; Chiang et al.
2011; Stewart et al. 2014), while an ovarian high-
grade endometrioid stromal sarcoma was reported
to contain YWHAE-NUTM2B gene fusion
(Kikuchi et al. 2017).
Differential Diagnosis
Ovarian endometrioid stromal sarcomas should
be distinguished from metastatic sarcoma of uterine origin, extrauterine Müllerian adenosarcoma,
sarcomatous component of carcinosarcoma, sex
cord-stromal tumors like fibromas, thecomas, and
adult granulosa cell tumors (AGCT), and other
metastatic sarcomas.
Thorough pathologic examination of the uterine body is crucial to rule out metastasis to the
ovary, as morphology will be similar. Metastatic
endometrial stromal sarcomas tend to involve the
ovaries bilaterally. In addition, thorough examination of the ovarian tumors may provide clues to
the diagnosis, for example, finding a malignant
glandular component would prove the tumor to be
a carcinosarcoma or either ovarian or extraovarian
origin. Furthermore, finding diffusely entrapped
glandular component with periglandul ar condensation supports the diagnosis of Mülleri an
adenosarcomas rather than ovarian endometrioid
stromal sarcomas, which can have just focally
entrapped glandular elements.
The presence of epithelial elements should also
raise the possibility of carcinosarcoma, whether
primary ovarian or metastatic. Careful examination of this component to rule out any malignant
changes is warranted.
Distinguishing ovarian endometrioid stromal
sarcomas from the more common sex cordstromal tumors may be more difficult because of
the possible shared morphology. Therefore, careful examination of the tumor with possible implementation of ancillary stains and molecular
studies may be indicated. Ovarian fibromas, one
of the common ovarian neoplasms, share similar
demographics with ovarian endometrioid stromal
sarcomas and show similar storiform pattern of
cellular spindle cell tumor with collagenous background and hyaline plaques. However, fibromas
would generally exhibit areas of tightly whorled
spindle cells with elongated nuclei resembling
normal ovarian cortex. Fibromas lack the abundant arteriolar proliferation typical for endometrioid stromal sarcomas. Thecomas are more
pale tumors with tumor cells containing more
abundant cytoplasm. The presence of extraovarian tumor extension and endometriosis facilitate the diagnosis of endometrioid stromal
sarcoma rather than fibromas or thecomas. As
some endometrioid stromal sarcomas demonstrate
sex cord-stromal differentiation with possible
nuclear grooves and focal expression of sex
cord-stromal immunohistochemical markers,
AGCT can be distinguished from endometrioid
stromal sarcomas based on the growth pattern of
the tumor cells. AGCT generally show other
intermingled patterns such as follicular growth
and Call-Exner bodies which are not features of
endometrioid stromal sarcomas. Nuclear grooves
are more diffuse in AGCT. All sex cord-s tromal
tumors tend to show diffuse expression of SF1,
inhibin, calretinin, and other sex cord-stromal
markers, and only weak and limited expression
of CD10. They lack the characteristic gene fusions
that can be found in endometrioid stromal sarcomas but rather harbor more specific gene changes,
e.g., FOXL2 mutations in AGCT.
Smooth muscle differentiation may render
endometrioid stromal sarcomas resembling
smooth muscle tumors, especially in undersampled tumors. This can be further complicated
by the presence of focal expression of smooth
muscle immunohist ochemistry markers. Nonetheless, the presence of classical endometrial
stromal-type tissue on routine microscopy and
immunohistochemistry would help confirm the
diagnosis of endometrioid stromal sarcomas.
Metastatic GIST is another important diagnosis
to exclude. In contrast to the infiltrative, monomorphic plump spindle cells with arteriolar proliferation of endometrioid stromal sarcomas,
GISTs show sheets and fascicles and bundles of
epithelioid to spindle cells in a hyalinized or
myxoid stroma with at least focal nuclear palisades that lack the characteristic vascular proliferation. Immunohistochemically, GISTs express
DOG-1 and c-Kit and carry mutations in KIT or
PDGFRA genes (Masand et al. 2013).
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Ovarian Leiomyoma
Synonyms
Leiomyoma of ovary.
Definition
Ovarian leiomyoma is a benign smooth muscle
tumor of the ovary.
Clinical Features
• Incidence
These tumors are rare and probably
underreported.
• Age
Ovarian leiomyomas can be found in a wide
range of premenopausal and postmenopausal
women, ranging from 3 to 63 years of age.
• Symptoms
Patients with ovarian leiomyoma usually present with nonspecific symptoms similar to
those of other ovarian tumors. These include
abdominal swelling, abdominal pain, and
bowel obstruction, or as torsion. They can
also be diagno sed incidentally by imaging for
unrelated conditions or complaints.
• Treatment
If needed, these tumors may be resected.
• Outcome
There is limited data on the behavior of ovarian
leiomyoma, but they are generally benign
(Lerwill et al. 2004).
Macroscopy
Ovarian leiomyomas are usually unilateral but
rarely are bilateral (Kandalaft and Esteban
1992). They are composed of well-circumscribed
firm, tan-white tumors with whorled nodular cut
surfaces, with a wide range of dimensions. Areas
of hemorrhage or necrosis may be present, especially in cases complicated by torsion.
Microscopy
The tumor is composed of intersecting fascicles of
bland spindle cells, composed of moderate
amount of eosinophilic cytoplasm with oval or
blunt “cigar-shaped” nuclei. Cytoplasmic
vacuolization may be focally present. The spindle
cells may be present in a hyalinized, edematous,
or myxoid stroma. Cellular variants can be seen.
Less commonly do the tumors exhibit marked
cytologic atypia with giant tumor cells in an otherwise bland smooth muscle proliferation
(atypical leiomyoma) or increased mitotic activity. Other variants, such as leiomyoma with apoplectic changes, and lipoleiomyoma, may also be
seen (Fig. 2).
Immunophenotype
Like other smooth muscle tumors, ovarian
leiomyomas express markers of smooth muscle
differentiation such as smooth muscle actin
(SMA), desmin, and caldesmon.
Molecular Features
Little is known about the molecular features of
ovarian leiomyomas. Mutations in mediator complex subunit 12 (MED12) were identified in a
small series of these tumors, notably clonally different from synchronous uterine leiomyomas
(Li et al. 2018).
Differential Diagnosis
Ovarian leiomyomas should be distinguished
from parasitic leiomyomas of uterine origin,
leiomyosarcomas, ovarian fibromas, metastatic
gastrointestinal stromal tumors (GIST), and
others.
Distinguishing primary ovarian leiomyomas
from parasitic uterine leiomyomas may be challenging as ovarian leiomyomas occur frequently
in association with uterine body leiomyomas. The
location of the ovarian tumor in close proximity to
the uterine serosa and the presence of multiple
serosal pedunculated uterine leiomyomas may
favor a diagnosis of a parasitic leiomyoma rather
than a primary ovarian leiomyoma.
Ovarian leiomyosarcomas generally exhibit
two of the three classical histologic features of
malignant smooth muscle tumors, i.e., diffuse
moderate to severe cytologic atypia, mitotic activity of at least 10 per 10 high-power fields, and
tumor necrosis. However, rare examples of atypical tumors with less mitotic activity and without
tumor necrosis may portray malignant behavi or
(Lerwill et al. 2004). When the smoo th muscle
tumor shows features of malignancy, a metastasis
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Mesenchymal Tumors, Pathology of the Ovary,
Fig. 2 Ovarian leiomyoma showing circumscribed prolif-
eration of bundles of benign smooth muscles (a) that are
from the uterine body or other sites should be
excluded by careful pathologic examination.
Ovarian leiomyomas, especially when combined with hyalinized stroma, may resemble the
more common ovarian fibromas. However, the
latter generally lack areas of typical smooth muscle differentiation, lack diffuse expression of
smooth muscle markers, and are rather positive
for sex cord-stromal immunohistochemical
marker such as SF1, inhibin, and calretinin.
Metastatic GIST can morphologically mimic
ovarian leiomyoma with fascicular growth of
spindle cells. GISTs tend to have also epithelioid
cells, with some degree of nuclear palisading,
expressing DOG1 and c-KIT, while their expression of smooth muscle markers is less diffuse.
They also carry specific mutations in KIT or
PDGFRA genes.
The rare ovarian endometrioid stromal sarcoma or metastatic endometrial stromal sarcoma
of uterine origin can mimic cellular leiomyomas.
However, these tumors generally lack the fascicular pattern of smooth muscle tumors and instead
show proliferative type endometrial stroma with
the characteristic arteriolar proliferation.
positive for smooth muscle markers (b) and negative for
sex cord-stromal tumors (c)
Immunohistochemically, they are positive CD10
and only focally for smooth muscle markers.
Ovarian Leiomyosarcoma
Synonyms
Leiomyosarcoma of ovary.
Definition
Ovarian leiomyosarcoma is a malignant smooth
muscle tumor of ovary.
Clinical Features
• Incidence
These tumors are rare.
• Age
Ovarian leiomyosarcoma have been reported
in a wide range of premenopausal and postmenopausal women, ranging from 25 to
82 years of age.
• Symptoms
Patients with ovarian leiomyosarcoma usually
present with nonspecific symptoms similar to
those of other ovarian tumors. These include
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abdominal swelling, abdominal pain, and
bowel obstruction, or as torsion.
• Treatment
The main treatment is surgical debulking
including hysterectomy and resection of all
extraovarian tumor deposits. There is no
defined role for adjuvant therapy. Recurrent
or metastatic disease may be treated with sur-
gery, radiation, or chemotherapy (using regi-
mens containing doxorubicin +/ ifosfamide,
gemcitabine-docetaxel, trabectedin, and plati-
num salts) (Cojocaru et al. 2021).
• Outcome
Like their uterine counterparts, ovarian
leiomyosarcomas are aggressive tumors. The
majority of the tumor recurs within 19 months
after resection. All reported patients with ovar-
ian leiomyosarcoma die of their disease within
24 months from diagnosis. Tumor stage is
seemingly the only prognostic marker in these
rare tumors; the median survival was 14, 18,
and 63 months for FIGO stage III/IV, stage II,
and stage I, respectively (Furutake et al. 2018).
Macroscopy
Ovarian leiomyosarcomas are usually unilateral
but can be bilateral. They form firm to soft nodules with gray-tan to yellow fleshy cut surface like
leiomyosarcomas of uterine corpus. The tumor
size has been reported to range from 4 to 30 cm
(Lerwill et al. 2004). Cystic change, hemorrhage,
and gross necrosis can be seen.
Microscopy
Ovarian leiomyosarcomas resemble their uterine
counterparts; they demonstrate smooth musc le
differentiation, exhibited by intersecting fascicles
of spindle cells with abundant eosinophilic cytoplasm and blunted nuclei. Similarly, a diagnosis of
leiomyosarcoma can be achieved in the presen ce
of two of the following three criteria: diffuse
moderate to severe cytologic atypia, mitotic activity of 10 or more per 10 high-power fields, and
tumor necrosis. Atypical mitotic figures can be
seen. In the absence of tumor necrosis but with a
mitotic count of 5–9 mitoses, a diagnosis of
benign leiomyoma with bizarre nuclei should be
made with caution as more than half of such
tumors have reportedly behaved as malignant
tumors (Lerwill et al. 2004). Myxoid variants
have been reported, demonstrating variably cellular tumors with atypical spindle cells in myxoid
matrix. Mitotic activity of these tumors was congruent to tumor cellularity. Tumor necrosis may
be seen.
Immunophenotype
Like other smooth muscle tumors, ovarian
leiomyosarcomas express markers of smooth
muscle differentiation such as smooth muscle
actin (SMA), desmin, and caldesmon. Estrogen
and progesterone receptors can also be positive.
Molecular Features
There are no known genetic changes in ovarian
leiomyosarcomas.
Differential Diagnosis
Ovarian leiomyosarcoma should be distinguished
from metastatic leiomyosarcoma of uterine origin,
sarcomatoid sex cord-stromal tumors of ovary,
and other metastatic sarcomas and sarcomatoid
carcinomas.
Hysterectomy and pathologic examination of
the uterus is paramount in ovarian leiomyosarcoma,
not only for therapeutic reasons but also to confirm
that the ovarian tumor is not a metastasis from the
more common uterine leiomyosarcoma.
When a high-grade sarcoma is encountered
within the ovary, the differential diagnosis may
include ovarian sex cord-stromal tumors with sarcomatous differentiation, e.g., adult granulosa cell
tumor with sarcomatoid differentiation or poorly
differentiated Sertoli-Leydig cell tumor. Features
that favor a sex cord-stromal tumor include the
presence of classical histologic sex cord-stromal
differentiation, e.g., the variable architectural patterns and Call-Exner bodies of adult granulosa
cell tumors, or well-differentiated Sertoli and
Leydig cell elements. Morphology assessment
may be aided by a panel of immunohistochemistry
for smooth muscle and sex cord differentiation,
albeit that poorly differentiated tumor may lose
their expected markers of differentiation. Molecular analysis may be considered for ambiguous
cases, targeting mutations in FOXL2 gene for
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adult granulosa cell tumors and DICER-1 gene for
Sertoli-Leydig cell tumors.
Areas resembling smooth muscle differentiation may also be seen in other metastatic sarcomas, and the absence of unequivocal evidence for
smooth muscle differentiation, an attempt may be
made to exclude other metastatic sarcomas
through correlation with clinical-radiologic data,
immunohistochemistry, and molecular changes if
applicable.
Epithelioid areas may be seen in
leiomyosarcomas, and cytokeratins can be focally
expressed in the tumor. Other considerations for
these areas include focal sex cord-stromal differentiation as discussed above. In addition, the possibility of a carcinoma with spindle cell
differentiation or carcinosarcoma should be
investigated.
Ovarian Myxoma
Synonyms
Myxoma of ovary.
Definition
Ovarian myxoma is a benign tumor of ovary with
myxoid matrix, likely unrelated to myxomas arising in other body sites.
Clinical Features
• Incidence
These tumors are extremely rare.
• Age
Ovarian myxomas have been predominantly in
premenopausal and premenarchal women,
ranging from 12 to 45 years of age, with rare
cases reported beyond that age range.
• Symptoms
Patients with ovarian myxoma usually present
with nonspecific symptoms similar to those of
other ovarian tumors. These include abdominal
swelling, abdominal pain, and bowel obstruc-
tion, or as torsion.
• Treatment
Simple surgical resection may be indicated to
confirm the diagnosis and prevent complica-
tions of large tumors.
• Outcome
The limited data suggest a benign uneventful
course after initial surgical resection (Roth
et al. 2013).
Macroscopy
Ovarian myxomas usually present as a unilateral
tumor, ranging in size from 5–22 cm (Eichhorn
and Scully 1991). The main tumor component is
composed of cystic tumor with gelatinous material. This is usually associated with a solid whitegray to yellow component.
Microscopy
The myxoma is composed of well-circumscribed,
variable cellular growth of bland oval to stellate
cells admixed in a pale basophilic matrix, without
significant atypia or mitotic activity. Thin-walled
blood vessels and scattered collagen bundles can
be seen. The myxoid matrix stains positive for
mucopolysaccharides using Hale colloidal iron.
Microcystic spaces may form within the tumor.
These tumors commonly arise in close association
with sex cord-stromal tumors, such as sclerosing
stromal tumors, even sharing the same tumor capsule with them.
Immunophenotype
The limited analysis of these tumors indicate that
ovarian myxomas may express smooth muscle
actin (SMA) and vimentin, but are generally negative for inhibin, desmin, cytokeratins, S100,
neurofilament, Leu-7, and factor VIII-related
antigen.
Molecular Features
There are no known genetic changes in ovarian
myxomas.
Differential Diagnosis
Ovarian myxomas should be distinguished from
massive ovarian edema, myxoid degeneration of a
tumor, and low-grade sarcomas with myxoid differentiation. Massive ovarian edema can have
loose paucicellular areas with thin-walled blood
vessels, reminiscent of the loose areas found in
myxomas. However, in contrast, massive ovarian
edema does not form distinct or encapsulated
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