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56 Benign Epithelial Tumors and Tumor-Like Lesions, Pathology of the Cervix
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Benign Epithelial Tumors and Tumor-Like Lesions, Pathology of the Vulva 57
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Benign Epithelial Tumors and
Tumor-Like Lesions,
Pathology of the Vulva
Aleodor Andea
Department of Pathology, University of
Michigan, Ann Arbor, MI, USA
Condyloma Acuminatum
Synonyms
Low-grade squamous intraepithelial lesion
(LGSIL) with condylomatous features, vulvar
intraepithelial neoplasia I (VIN I), and
genital wart.
Definition
Sexually transmitted, benign proliferative squamous lesion with warty exophytic morphology
or flat (non-warty), caused by human papillomavirus (HPV) infection.
Clinical Features
• Incidence
HPV infection and condyloma acuminatum are
very common. About 20–40% of sexually
active women are infected with HPV with 5.5
million new HPV infections per year in US for
a total prevalence of 20 million. The incidence
of genital condylomas has increased among
women from 0.013% in 1950 to 1% currently
(Gall 2001).
• Age
Condyloma acuminatum has a predilection for
young, sexually active women in the second–
third decade of life (Gall 2001).
• Site
Typically involves vulvar skin, labia minora,
vestibule, and the medial aspect of labia
majora.
• Treatment
Various methods are used to remove condylomas including surgical excision, laser ablation,
cryotherapy, and topical application of
imiquimod, 5-fluorouracil, or podophyllin
(O’Mahony 2005).
• Outcome
Condylomas are benign; however, patients
may suffer from m ultiple recurrences. Some
lesions will regress without intervention, but
the viral infection persists and factors that
produce i mmunosuppress ion may lead to
recurrences. Some condylomas are asso ciated with high-risk HPV, and this may
account for progression of some lesions to
high-grade squamous intraepithelial lesions
(HGSIL).
Macroscopy
Usually, multiple lesions are present involving
moist areas of the vulva. Two major types can be
encountered: exophytic condyloma (condyloma
acuminatum) and flat condyloma. The exophytic
type presents as “cauliflower-like” masses with
velvety, fleshy appearance (Fig. 1). The flat condylomas are less common and appear as white,
erythematous, or hyperpigmented papules or
macules.
Microscopy
Exophytic condylomas demonstrate a papillary
architecture at low magnification with bulbous
rete and an undulating interface with the dermis
or submucosa (Fig. 2). The lesion shows hyperkeratosis and parakeratosis with accentuation of
the granular layer. Foci of keratinocytes with
enlarged and irregular nuclei and perinuclear
clear halos representing HPV cytopathic changes
or koilocytosis are seen in the superficial epithelial
layers (Fig. 3). Flat condylomas lack the papillary
architecture but demonstrate acanthosis and
hyperkeratosis; they are less common in the
vulva compared to cervix (Medeiros et al. 2005;
Yang et al. 2017).
B
58 Benign Epithelial Tumors and Tumor-Like Lesions, Pathology of the Vulva
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Benign Epithelial Tumors and Tumor-Like Lesions,
Pathology of the Vulva, Fig. 3 Condyloma
acuminatum at high magnification condylomas show
hyperkeratosis and parakeratosis with foci of koilocytosis
Benign Epithelial Tumors and Tumor-Like Lesions,
Pathology of the Vulva, Fig. 1 Condylomas presenting
as multiple “cauliflower-like” lesions with an exophytic
appearance
Benign Epithelial Tumors and Tumor-Like Lesions,
Pathology of the Vulva, Fig. 2 Condyloma
acuminatum low magnification shows a papillary architecture with acanthosis, bulbous rete, and an undulating interface with the dermis or submucosa
Immunophenotype
Immunohistochemistry for p16 shows typically
patchy staining in exophytic condylomas which
helps to differentiate from HGSIL (Walts et al.
2006). It can be diffuse with “block pattern” in
flat condylomas limiting the utility of p16 in this
context in differentiating LGSIL from HGSIL
(Lewis et al. 2017).
Molecular Features
Exophytic condylomas are caused by infection
with low-risk HPV, serotypes 6 and 11, and can
be identified by PCR of in situ hybridization (Gall
2001; Logani et al. 2003). Flat condylomas can be
caused by not only low-risk but also high-risk
HPV (Logani et al. 2003; Srodon et al. 2006).
Differential Diagnosis
Fibroepithelial stromal polyps can be papillomatous; however, they lack epithelial acanthosis and
koilocytosis. Seborrheic keratosis (SK) demonstrates a basaloid morphology and keratin pseudocysts. However, considering that HPV can be
demonstrated in cases of vulvar SK, some consider
these lesions to represent a variant of condyloma
(Bai et al. 2003;Medeirosetal.2005). HGSIL and
squamous cell carcinoma demonstrate nuclear
atypia and mitotic figures involving the entire
thickness of the epidermis. Verrucous carcinoma
isarareformofvulvarsquamouscellcarcinoma
that may resemble condyloma especially in small
biopsies. As opposed to condyloma, verrucous carcinoma demonstrates an endophytic pushing
growth in the stroma and lacks koilocytosis
Benign Epithelial Tumors and Tumor-Like Lesions, Pathology of the Vulva 59
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(Yang et al. 2017). Finally, condyloma lata represents a type of secondary syphilis involving the
vulva, characterized by a verrucous morphology
that resembles condyloma acuminatum. As
opposed to condyloma acuminatum, condyloma
lata demonstrates an inflammatory infiltrate with
plasma cells and endothelial swelling and does not
show koilocytosis. In addition, spirochetes can be
identified with Steiner or spirochete immunohistochemical stains.
Seborrheic keratosis
Definition
Benign proliferation of keratinocytes.
Synonyms
Condyloma with features of seborrheic keratosis
(SK).
Clinical Features
• Incidence
SKs are relatively common lesions.
• Age
SKs can be seen in all age groups.
• Site
No site preference in the vulvar area.
• Treatment
For most SKs no treatment is needed except for
cosmetic reasons. Methods of removal include
surgical excision, laser ablation, and cryotherapy.
• Outcome
SKs are benign lesions. The subset of SKs
associated with HPV can recur.
Macroscopy
SKs present as papules with stuck on appearance
ranging in size from few millimeters to several
centimeters. Some SKs are pigmented, mimicking
a melanocytic neoplasm.
Microscopy
SKs are characterized by acanthosis,
papillomatosis, hyperkeratosis, and epidermal
pseudohorn cysts representing invagination of
the surface epidermis. The base is flat and the
lesion is usually raised above the adjacent epidermis. Several architectural patterns can be seen:
clonal, reticular, verrucous, and hyperkeratotic
(Fig. 4).
Immunophenotype
SKs show only patchy p16 staining (Bai
et al. 2003).
Molecular Features
Few studies have found that a subset of SKs is
associated with low-risk HPV (usually HPV 6)
(Bai et al. 2003; Reutter et al. 2014). Some authors
regard these lesions as a variant of condyloma
(condyloma with features as SK), especially in
young women.
B
Benign Epithelial Tumors
and Tumor-Like Lesions,
Pathology of the Vulva,
Fig. 4 Seborrheic keratosis
the lesion shows acanthosis,
papillomatosis, and
pseudohorn cysts
60 Benign Glandular Lesions, Pathology of the Vagina
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Differential Diagnosis
The main differential diagnosis is with condyloma. As mentioned above, a subset of SKs is
HPV related and likely represent a variant of condyloma. The presence of papilomatosis resembles
an epidermal nevus. The presence of a linear
distribution and young age of the patients favor
an epidermal nevus.
References and Further Reading
Bai, H., Cviko, A., Granter, S., Yuan, L., Betensky, R. A.,
& Crum, C. P. (2003). Immunophenotypic and viral
(human papillomavirus) correlates of vulvar seborrheic
keratosis. Human Pathology, 34(6), 559–564. https://
doi.org/10.1016/s0046-8177(03)00184-9.
Gall, S. A. (2001). Female genital warts: Global trends and
treatments. Infectious Diseases in Obstetrics and Gyne-
cology, 9(3), 149– 154. https://doi.org/10.1155/
S1064744901000278.
Lewis,N.,Blanco,L.Z.,Jr.,&Maniar,K.P.(2017).p16
expression and biological b ehavior of flat vulvar
Low-grade Squamous Intraepithelial Lesions
(LSIL). International Journal of Gyneco logi cal
Pathology, 36(5), 486–492. https://doi.org/10.1097/
PGP.0000000000000364.
Logani, S., Lu, D., Quint, W. G., Ellenson, L. H., & Pirog,
E. C. (2003). Low-grade vulvar andvaginal intraepithelial
neoplasia: Correlation of histologic features with human
papillomavirus DNA detection and MIB-1
immunostaining. Modern Pathology, 16(8), 735–741.
https://doi.org/10.1097/01.MP.0000081051.55284.2A.
Medeiros, F., Nascimento, A. F., & Crum, C. P. (2005).
Early vulvar squamous neoplasia: Advances in classification, diagnosis, and differential diagnosis.
Advances in Anatomic Pathology, 12(1), 20–26.
https://doi.org/10.1097/01.pqp.0000151268.72556.f3.
O’Mahony, C. (2005). Genital warts: Current and future
management options. American Journal of Clinical
Dermatology, 6(4), 239–243. https://doi.org/10.2165/
00128071-200506040-00004.
Reutter, J. C., Geisinger, K. R., & Laudadio, J. (2014).
Vulvar seborrheic keratosis: Is there a relationship to
human papillomavirus? Journal of Lower Genital Tract
Disease, 18(2), 190–194. https://doi.org/10.1097/LGT.
0b013e3182952357.
Srodon, M., Stoler, M. H., Baber, G. B., & Kurman, R. J.
(2006). The distribution of low and high-risk HPV
types in vulvar and vaginal intraepithelial neoplasia
(VIN and VaIN). The American Journal of Surgical
Pathology, 30(12), 1513–1518. https://doi.org/10.
1097/01.pas.0000213291.96401.48.
Walts, A. E., Lechago, J., & Bose, S. (2006). P16 and Ki67
immunostaining is a useful adjunct in the assessment of
biopsies for HPV-associated anal intraepithelial neoplasia. The American Journal of Surgical Pathology,
30(7), 795– 801. https://doi.org/10.1097/01.pas.
0000208283.14044.a9.
Yang, E. J., Kong, C. S., & Longacre, T. A. (2017). Vulvar
and anal intraepithelial neoplasia: Terminology, diagnosis, and ancillary studies. Advances in Anatomic
Pathology, 24(3), 136–150. https://doi.org/10.1097/
PAP.0000000000000149.
Benign Glandular Lesions,
Pathology of the Vagina
Raji Ganesan
Birmingham Women’s and Children’s NHS Trust,
Birmingham, UK
Endometriosis
Definition
The presence of endometrial stroma with or without glands.
Clinical Features
Superficial endometriosis may present w ith vaginal
bleeding. Deep endometriosis, associated with pelvic endometriosis, presents with pain, dyspareunia,
and sometimes pressure symptoms. Rarely, polypoid vaginal masses may be seen (Parker et al., 2004).
• Incidence
Deep vaginal endometriosis is more common.
• Age
Most women present premenopausally.
• Site
The upper half of the vagina is the common
location. Polypoid endometriosis presents in
the posterior wall.
• Treatment
Treatment with hormones or excision of the
lesion is the initial treatment. Deep endometriosis may require complex surgery (Angioli
et al., 2014).
Benign Glandular Lesions, Pathology of the Vagina 61
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• Macroscopy
Tissue may appear polypoid and/or
hemorrhagic. They may also present as polypoid, pink, or tan-colored masses.
• Microscopy
Endometrial-type glands and/or stroma are
seen. Lesions in pregnant women or in
hormone-treated cases may show stromal
decidualization.
• Differential Diagnosis
Superficial endometriosis with glands may
be mistaken for adenosis; however, the latter lacks endometrial stroma. Extensive
stromal decidualization with clearing of
cytoplasm maybe mistaken for clear cell
carcinoma. The latter sho ws nuclea r atypia
Benign Glandular Lesions, Pathology of the Vagina,
Fig. 1 Labeled superficial endometriosis. Endometrial
glands and stroma are seen in the subepithelial vaginal
tissue
and usually presents with papillary, glandular, and solid patterns. Polypoid endometriosis must be distinguished from
adenosarcoma. It lacks the periglandular
stromal condensation and hypercellularity,
stromal atypia, and intraglandular epithelial
protrusions seen in adenosarcoma (Figs. 1,
2,and3).
B
Vaginal Adenosis
Synonyms
None.
Definition
This is the presence of benign glandular epithelium in the vaginal squamous lining or in the
superficial lamina propria.
Clinical Features
It may present as a red granular area or may be
asymptomatic (Han et al., 2018).
• Incidence
It is an uncommon condition. It was seen in
offspring of women exposed to DES during
pregnancy (Herbst et al., 1975).
Benign Glandular Lesions, Pathology of the Vagina,
Fig. 2 Labeled deep endometriosis. Endometrial type
glands and stroma present deep in the vaginal tissue
Benign Glandular Lesions, Pathology of the Vagina,
Fig. 3 Labeled adenosis. The vaginal squamous epithe-
lium is partly replaced by benign glandular epithelium
62 Benign Squamous Lesions, Pathology of the Vagina
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• Age
Wide age range.
• Site
Adenosis associated with DES exposure is
more common in the upper two-thirds of the
vagina. Sporadic cases do not appear to have a
particular predilection.
• Treatment
There are reports of successful treatment by
cauterization (Cebesoy et al., 2007).
• Outcome
DES-associated adenosis appears to regress by
squamous metaplasia (Robboy et al., 1981).
Other forms of adenosis may progress to clear
cell and gastric-type adenocarcinoma (Wong
et al., 2018).
• Macroscopy
The samples are usually biopsies and have a
nonspecific appearance.
• Microscopy
The squamous epithelium may be partly or
completely replaced by mucinous or nonmucinous (tuboendometrioid) epithelium.
Definitionally, endometrial type stroma must
be absent. The mucinous epithelium may be
endocervical or gastric type. Intestinal type
differentiation with goblet cells can be seen.
Atypical adenosis – significant cytological
atypia without invasion – has been described
(Robboy et al., 1984).
• Differential Diagnosis
The main differential diagno sis is endometriosis, which is differentiated by the presence of
endometrial type stroma.
Han, T., Jin, Y., Li, Y., Bi, Y., & Pan, L. (2018). Clinicopath-
ologic features and outcomes of primary vaginal adenosis
as a dermatologic and gynecolo gic burden: A retrospective study. Medicine (Baltimor e), 97(49), e13470.
Herbst, A. L., Poskanzer, D. C., Robboy, S. J., Friedlander,
L., & Scully, R. E. (1975). Prenatal exposure to stilbestrol. A prospective comparison of exposed female offspring with unexposed controls. New England Journal
of Medicine, 292(7), 334–339.
Parker, R. L., Dadmanesh, F., Young, R. H., & Clement,
P. B. (2004). Polypoid endometriosis: A clinicopathologic analysis of 24 cases and a review of the literature.
American Journal of Surgical Pathology, 28(3),
285–297.
Robboy, S. J., Szyfelbein, W. M., Goellner, J. R., Kaufman,
R. H., Taft, P. D., Richard, R. M., Gaffey, T. A., Prat, J.,
Virata, R., Hatab, P. A., McGorray, S. P., Noller, K. L.,
Townsend, D., Labarthe, D., & Barnes, A. B. (1981).
Dysplasia and cytologic findings in 4,589 young
women enrolled in diethylstilbestrol-adenosis
(DESAD) project. American Journal of Obstetrics
and Gynecology, 140(5), 579–586.
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.
Benign Squamous Lesions,
Pathology of the Vagina
Jason Wong
Department of Cellular Pathology, East Suffolk
and North Essex NHS Foundation Trust, Ipswich,
UK
References and Further Reading
Angioli, R., De Cicco Nardone, C., Cafà, E. V., Plotti, F.,
Muzii, L., Montera, R., Guzzo, F., Luvero, D., &
Terranova, C. (2014). Surgical treatment of
rectovaginal endometriosis with extensive vaginal infiltration: Results of a systematic three-step vaginolaparoscopic approach. European Journal of Obstetrics
& Gynecology and Reproductive Biology, 173,83–87.
Cebesoy, F. B., Kutlar, I., & Aydin, A. (2007). Vaginal
adenosis successfully treated with simple unipolar cauterization. Journal of Nation al Medical Association, 99(2),
166–167.
Condyloma Acuminatum
Definition
They are benign, flat, or verruciform lesions
caused by low-risk HPV.
Clinical Features
They may be asymptomatic and incidental. If at
the introitus, they may present with itching and
irritation.
Benign Tumors, Pathology of the Broad Ligament and Other Uterine Ligaments 63
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• Incidence
They are rare in the vagina.
• Age
Generally seen in young, sexually active
adults.
• Site
Lower vagina and introitus.
• Treatment
Nonsurgical treatment including observation,
local excision, topical imiquimod, and laser
ablation.
Outcome
Multiple recurrences are not common
(Widschwendter et al. 2019).
Macroscopy
Hyperkeratotic flat or raised lesions.
Microscopy
squamous lesions of the anogenital region. Seminars in
Diagnostic Pathology, 32(5), 409–418.
Widschwendter, A., Böttcher, B., Riedl, D., Coban, S., Mutz-
Dehbalaie, I., Matteucci Gothe, R., Ciresa-König, A.,
Marth, C., & Fessler, S. (2019). Recurrence of genitals
warts in pre-HPV vaccine era after laser treatment.
Archives of Gynecology and Obstetrics, 300, 661–668.
Benign Tumors, Pathology of
the Broad Ligament and Other
Uterine Ligaments
Isabel Alvarado-Cabrero
Department of Pathology, Mexican Oncology
Hospital, Mexico City, Mexico
Serous Cystadenoma of the Broad
Ligament
Definition
Benign serous tumor composed of cell s resembling fallopian tube epithelium.
B
Acanthosis, blunt papillomatosis, tiered parakeratosis, hypergranulosis, hyperkeratosis, and
koilocytosis can be seen. The prominence of the
features correlates with the age of the lesion, being
more prominent in younger lesions.
Immunophenotype
P16 staining is nonblock. Low-risk HPV (usually
HPV6 and HPV11) can be detected by PCR or in
situ hybridization (Pirog 2015).
Differential Diagnosis
None.
References
Pirog, E. C. (2015). Immunohistochemistry and in situ
hybridization for the diagnosis and classification of
Clinical Features
• Incidence
The serous cystadenoma is the most common
type of mullerian-derived epithelial tumor in
this location.
• Age
The age of presentation shows a wide range
from 19 to 73 years.
• Site
Broad ligament.
• Clinical Presentation
These lesions are an incidental finding at the
time of surgery for another gynecological disorder, or patients can present with a pelvic mass.
• Treatment
Patients are treated with surgery.
• Outcome
These are benign tumors.
Macroscopy
Most tumors are unilateral cysts ranging up to
13 cm in diameter.
64 Benign Tumors, Pathology of the Broad Ligament and Other Uterine Ligaments
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Microscopy
These tumors differ from nonneoplastic cysts of
serous type by the presence of a thick wall composed of cellular stroma in the former.
Molecular Features
Not clinically relevant.
Leiomyoma
Definition
A benign smooth muscle tumor arising from the
broad and other uterine ligaments.
Clinical Features
• Incidence
Leiomyoma is the most common solid tumor of
the broad ligament and uterine ligaments.
Because of their proximity to the fallopian tube
and uterus, it is often difficult to determine the
site of origin of leiomyomas (Scully et al. 1998).
• Age
Leiomyoma is present in 20–25% of women
over 30 years of age, rising to >40% in women
older than 40 years (Young 2007).
• Site
Broad and other uterine ligaments.
• Clinical Presentation
Most patients are asymptomatic. When symptoms occur, they usually correlate with their
size or associate degenerative changes.
Abdominal pain seconda ry to acute hemorrhage may occur, especially in those
leiomyomas that undergo torsion (Gowri et al.
1992). Massive ascites and bilateral pleural
effusion have been described in association
with broad ligament leiomyoma and with
para-ovarian fibroma (pseudo-Meigs syndrome) (Scully et al. 1998).
Five inguinal leiomyomas of the round ligament have been reported in women with a
median age of 52 years (Patil et al. 2011).
• Treatment
Surgical excision is curative.
• Outcome
This tumor is benign.
Macroscopy
Most tumors are solid masses, but a few cases
showing pseudocystic degeneration have been
reported. They may range from microscopic to
more than 30 cm (Gowri et al. 1992).
Microscopy
Leiomyomas in the broad ligament are identical to
those occurring in the uterus, including histological patterns such as atypical leiomyomas or
leiomyomas with epithelioid morphology
(Matthews et al. 2003).
Molecular Features
Not clinically relevant.
Differential Diagnosis
Leiomyomas of the adnexa and uterus are distinguished from broad ligament leiomyomas by their
anatomic location. Usual leiomyomas are
straightforward; however, several leiomyoma variants can be confused with a leiomyosarcoma
(The uterine criteria for malignancy have been
proposed for the classification of smooth muscle
tumors at this location) (Matthews et al. 2003).
References and Further Reading
Gowri, V., Sudheendra, R., Oumachigui, A., & Sankaran,
V. (1992). Giant broad ligament leiomyoma. Interna-
tional Joirnal of Gynaecology & Obstetyrics, 37,
207–210.
Matthews, T., Amanuel, B., & Tsokos, N. (2003). Atypical
leiomyoma of the broad ligament. Australian and
New Zealand Journal of Obstetrics and Gynaecology,
43, 326–328.
Patil, D. T., Laskin, W. B., Fetsch, J. F., & Miettinen,
M. (2011). Inguinal smooth muscle tumors in
women-a dichotomous group consisting of Mulleriantype leiomyomas and soft tissue leiomyosarcomas: An
analysis of 55 cases. The American Journal of Surgical
Pathology, 35, 315–324.
Scully, R. E., Bonfiglio, T. A., Kurman, R. J., Silverberg,
S. G., & Wilkinson, E. J. (Eds.). (1994). Histological
typing of female genital tract tumors. International
histological classification of tumours (2nd ed.).
Springer: Berlin/Heidelberg.
Scully, R. E., Young, R. H., & Clement, P. B. (Eds.).
(1998). Tumors of the ovary, maldeveloped gonads,
fallopian tube and broad ligament. Atlas of tumor
Benign Tumors, Pathology of the Fallopian Tube 65
https://t.me/med1917
pathology (3rd series, fascicle 23). Washington, DC:
Armed Forces Institute of Pathology.
Young, R. H. (2007). Neoplasms of the fallopian tube and
broad ligament: A selective survey including historical
perspectives and emphasizing recent developments.
Pathology, 39,112–124.
Benign Tumors, Pathology of
the Fallopian Tube
Isabel Alvarado-Cabrero
Department of Pathology, Mexican Oncology
Hospital, Mexico City, Mexico
Adenomatoid Tumor
Definition
Adenomatoid tumor is the most frequent benign
neoplasm of the fallopian tube. These tumors are
mesothelial in origin (Sangoi et al. 2009).
Clinical Features
• Incidence
These tumors are rare.
• Age
Adenomatoid tumors usually occur in women
who are in middle age or elderly. (Wachter
et al. 2011.
• Site
Fallopian Tube.
• Clinical Presentation
This tumor is almost always an incidental finding (Sangoi et al. 2009; Wachter et al. 2011).
• Treatment
Treatment is not needed (Terada 2012).
• Outcome
They are benign tumors (Sangoi et al. 2009;
Terada 2012).
• Macroscopy
Tubal adenomatoid tumors are wellcircumscribed, firm, masses. They typically
appear as a gray, white, or yellow nodular
swelling measuring 1–2 cm in diameter located
beneath the tubal serosa (Karpathiou
et al. 2020).
Microscopy
Tumors are characterized by anastomosing glandlike spaces that may show cribriforming and/or
slit-like, ovoid to round spaces reminiscent of
vascular structures. Cysts, signet-ring-like cells,
and less frequently papillae or solid growth are
also seen. A single tumor often displays more than
one pattern (Sangoi et al. 2009; Schwartz and
Longacre 2004).
Immunophenotype
The tumor cells are positive for AE1/AE3, CK7,
CAM 5.2, CK 18/19, calretinin, D2–40, WT1,
ER, and PR and negative for CK5/6 and
h-caldesmon (Terada 2012; Wachter et al. 2011).
Molecular Features
Adenomatoid tumors harbor somatic missense
mutations in the TRAF7 gene, which encodes
an E3 ubiquitin ligase belonging to the family
of tumor necrosis factor receptor-associated
factors (TRAFs). These mutations all clust er
into one of five recurrent hotspots within the
WD40 repeat domains at the C-terminus of the
protein (Goode et al. 2018; Karpathiou
et al. 2020).
Differential Diagnosis
Adenomatoid tumor should be distinguished
from adenocarcinoma, including signet-ring
cell carcinoma, as both tumors share an infiltrative growth, signet-ring like cells and luminal
basophilic secretions. The well-circumscribed
gross appearance, bland cytology, and lac k of
mitotic activity support a benign diagnosis.
Lipoleiomyoma should be considered in the differential diagnosis if the cystic spaces are larger
and resemble adipocy tes (Sangoi et al. 2009)
(Figs. 1 and 2).
Serous Adenofibroma
Definition
A benign neoplasm composed of broad fibrous
papillae lined by a single layer of tubal-type
epithelium.
B
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