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36 Benign Epithelial Tumors and Tumor-Like Lesions, Pathology of the Cervix
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mimic in situ adenocarcinoma human papillomavirus (HPV)-associated, especially at low-power
magnification. Endometriosis lacks atypia,
mitotic figures, and apoptotic bodies, which are
features pathognomonic for HPV-associated in
situ adenocarcinoma. P16, ERs, and PRs can
assist, with ERs and PRs being positive in endometriosis and p16 being negative (patchy) in contrast to adenocarcinoma in situ where ERs and
PRs are negative and p16 block-type is positive.
Also, BCL-2 is positive in endometriosis and
negative in adenocarcinoma in situ. HPV testing
will also be positive in the latter.
Benign Epithelial Tumors and Tumor-Like Lesions,
Pathology of the Cervix, Fig. 14 Large polypoid lesion
involving the cervix, mainly represented by endometrial
type of stroma, with rare endometrioid type of glands and
hemorrhage
On the other hand, stromal endometriosis, a
variant in which foci of endometriosis are devoid
of endometrial glands, needs to be differentiated,
if extensive and deeply located, from low-grade
endometrial stromal sarcoma, a tumor associated
with larger size, clinical symptoms, presence of
permeative growth, and vascular invasion. Sometimes, additional levels will show the presence of
rare endometrioid type of glands in endometriosis.
Another differential to consider in case of stromal endometriosis is Kaposi sarcoma, a very rare
tumor developing in the cervix, in immunoc ompromised patients. Kaposi sarcoma is characterized by a proliferation of spindle type of tumor
cells, arranged in fascicles and surrounding
slit-like spaces, containing red blood cells. The
tumor cells are positive for CD31 and CD34
which will facilitate the diagnosis. Finally, when
Benign Epithelial Tumors and Tumor-Like Lesions,
Pathology of the Cervix, Fig. 15 Cervical endometri-
osis: the glandular component is surrounded by a stromal
component, composed of small cells, with little cytoplasm
and oval to round nuclei, in association with hemosiderinladen macrophages
both glandular and stromal components are present, adenosarcoma has to be ruled out.
Adenosarcoma however is characterized by a
phyllodes-like architecture and hypercellular
cuffing of stromal cells around the glands.
Immunophenotype
Glands are positive for estrogen receptors (ERs),
progesterone receptors (PRs), and vimentin, while
stromal component is positive for CD10. BCL-2
is also positive in endometriosis.
Molecular Features
Not clinically relevant.
Differential Diagnosis
In case the stromal component is not well
represented or absent, dark-blue glands may
Inflammatory Lesions of the Uterine
Cervix
Synonyms
Cervicitis.
Definition
Inflammatory lesions of the cervix are classified
into two categories: non-infectious and infectious,
depending on the etiology (Jayakumar 2015).
They can occur in isolation, as part of an infection
Benign Epithelial Tumors and Tumor-Like Lesions, Pathology of the Cervix 37
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of the lower genital tract or in pelvic inflammatory
disease. Non-infectious cervi citis, which can be
acute or chronic are due to mechanical or chemical aggression and are characterized by a nonspecificinflammatory response. Of these
aggressions, the most common ones are produced
by foreign bodies, sanitary pads, diaphragms,
intrauterine contraceptive devices, and surgery.
Infectious cervicitis can be bacterial, viral, fungal,
and parasitic.
Clinical Features
• Incidence
Frequent.
• Age
Usually in reproductive age, but any age can be
involved.
Benign Epithelial Tumors and Tumor-Like Lesions,
Pathology of the Cervix, Fig. 16 Acute non-infectious
cervicitis characterized by inflammatory infiltrate with
neutrophilic polymorphonuclear cells, involving both cervical stroma and squamous epithelium
• Sex
Female.
• Site
Both ectocervix and endocervix are usually
involved.
• Treatment
Nonsurgical treatment is recommended in
most cases.
• Outcome
Excellent, in general, with effective treatment
resulting in complete resolution of the lesions.
In pregnant women however, cervicitis may
cause spontaneous abortion, premature delivery,
chorioamnionitis, or neonatal complications.
inflammatory infiltrate, with neutrophilic polymorphonuclear cells, involving both cervical
stroma and epithelium (Fig. 16). If the inflammation is severe and prolonged, these aspects are
accompanied by ulceration of the epithelium. In
chronic non-infectious cervicitis, there is an abundant inflammatory infiltrate, composed predominantly of lymphocytes, plasma cells, histiocytes,
associated with the formation of granulation tissue
and stromal fibrosis.
Regardless of their etiology, infectious cervici-
tis can affect the endocervical epithelium, causing
endocervicitis or the ectocervical squamous epithelium, causing exocervicitis. Some infectious
Macroscopy
The cervix appears swollen, with erythematous or
ulcerative areas, sometimes associated with puru-
agents can cause one or the other type of cervicitis, but there are infectious agents that can cause
both types of cervicitis.
lent endocervical discharge. In Herpes simplex
virus (HSV) infection , the lesion is characterized
by blisters, which grow rapidly in size and produce painful ulcers. The lesions are often located
not only on the cervix but also in the vagina,
perineum, and vulva. Other times, inflammatory
lesions of the cervix may form a mass (e.g., in
Human Papillomavirus infection, in the form of a
white exophytic lesion called condyloma
acuminatum) but can also be clinically inapparent.
• Bacterial infections: more commonly pro-
duced by Chlamydia and Neisseria gonorrhea.
Chlamydia trachomatis infection is character-
ized by a chronic inflammatory infiltrate,
sometimes with the appearance of follicular
cervicitis. Reactive squamous and endo-
cervical atypia can also be observed. In endo-
cervical or metaplastic cells, in some cases,
intracytoplasmic inclusions can be identified,
which on immunohistochemical stains, have
Microscopy
Acute non-infectious cervicitis is characterized by
stromal edema, vascular congestion, and
been shown to be Clamydia aggregates. The
diagnosis of cervicitis with Chlamydia
trachomatis is established on the basis of
B
38 Benign Epithelial Tumors and Tumor-Like Lesions, Pathology of the Cervix
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clinical appearance, culture, immunofluorescence, or enzyme-linked immunosorbent
assay (ELISA). Post-infectious complications
include pelvic inflammatory disease, tubal
infertility, and neonatal pneumonia. Infections
caused by Neisseria gonorrhea affect the endocervix and are characterized by the presence of
an inflammatory infiltrate in the stroma, while
the glandular epithelium undergoes degenerative, squamous, or necrotic changes. Sometimes the lumens of the glands contain
neutrophilic polymorphonuclear cells. Infections caused by Actinomyces israelii occur
mainly following surgery, abortion, the use of
uterine contraceptive device, or may spread to
the cervix as a result of parametrial or anal
infections. Microscopically, the lesion consists
of the formation of multiple granulomas,
consisting of neutrophilic polymorphonuclear
cells, in the center of which Gram-positive
filamentous structures are highlighted, presenting with peripheral palisade (Fig. 17 ). Cervical tuberculosis most often occurs following
a tubal and endometrial lesion and is secondary
to pulmonary tuberculosis. On microscopy, the
lesion is characterized by the presence of multiple necrotizing tuberculous granulomas, presenting with central caseous necrosis,
surrounded by epithelioid histiocytes, giant
multinucleated Langhans cells, and an
inflammatory lymphoplasmacytic infiltrate at
the peryphery. Acid-fast bacilli are highlighted
by a Ziehl–Neelsen stain.
• Viral infections: of the viral pathogens, human
papillomavirus (HPV) and herpes simplex
virus (HSV), have a predilection for squam ous
epithelium and produce characteristic morpho-
logical lesions. HPV 6 and 11 subtypes pro-
duce condyloma acuminatum, a benign
epithelial tumor which is usually multicentric
and involves the vulva, vagina, and cervix and
is characterized by koilocytes (this lesion is
extensively covered elsewhere in the book)
(Fig. 18). Herpes virus infection (both HSV-1
and HSV-2) can be diagnosed by cervical cul-
tures, serological examinations, and cytologi-
cal examination with Papanicolaou smears.
Microscopically, in the initial stage of infec-
tion, the squamous cells show enlarged nuclei,
with the appearance of “ground glass,” mar-
ginal chromatin, and sometimes the nuclei
have a vacuolated appearance. Binucleated or
Benign Epithelial Tumors and Tumor-Like Lesions,
Pathology of the Cervix, Fig. 17 Cervicitis with Acti-
nomyces israelii: granuloma consisting of neutrophilic
polymorphonuclear cells, in the center of which Grampositive structure is highlighted
Benign Epithelial Tumors and Tumor-Like Lesions,
Pathology of the Cervix, Fig. 18 Squamous cervical
epithelium with HPV infection: koilocytes are present
Benign Epithelial Tumors and Tumor-Like Lesions, Pathology of the Cervix 39
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multinucleated cells may occur. As the lesion
progresses, an intraepithelial, basal vesicle
forms, surrounded by cells with nuclei
containing eosinophilic inclusions, surrounded
by a clear halo, as well as degenerated, mononucleated, or multinucleated cells. Rupture of
the vesicle causes ulceration, and an intense
inflammatory infiltrate ap pears in the stroma.
After about 2 weeks, the ulceration area heals
spontaneously by re-epithelialization. In cervicitis caused by Cytomegalovirus, endocervical
cells are mainly affected but also endothelial
cells and stromal cells. The y contain characteristic intranuclear and intracytoplasmic basophilic or amphophilic inclusions. The
underlying stroma has an abundant
lymphoplasmacytic inflammatory infiltrate,
and fibrin thrombi within small blood vessels
can occur. The infection occurs mainly in
young pregnant women, and about 10% of
children born to these mothers have a congenital infection, but except for a lower birth
weight, children do not have other significant
abnormalities.
• Fungal infections are caused by Candida
albicans and are usually associated with infec-
tions of the vagina and vulva. Favoring factors
are alkalization of vaginal pH, antibiotic therapy, and diabetes. Microscopically, there is an
increased number of polymorpho-leukocytes
in the upper layers of the epithelium in association with fungal hyphae (identified by periodic acid-Schiff (PAS) stains). Aspergillus
infection occurs only in people with
compromised immunity.
• Parasitic infections:themostcommonpara-
sitic cervicitis is caused by Trichomonas
vaginalis and is associated with vaginitis.
Microscopically, an intense inflammatory
infiltrate is observed, associated with degenerative changes, intercellular edema, and
reparative atypia, both in the squamous and
in the endocervical epithelium. The diagnosis
is made by cytological examination on P ap
smear stains. Also, cervical schistosomiasis
(caused by Schistosoma mansoni)iswell
documented in endemic areas and is characterized by noncaseating granulomas, with
ova surrounded by multinucleated giant
cells and sometimes by extensive pseudoepitheliomatous hyperplasia of the cervical
squamous epithelium. Rare examples of cervicitis due to Entamoeba histolytica and
Trypanosoma cruzi (Chagas disease) have
been reported.
Immunophenotype
Not clinically relevant.
Molecular Features
Not clinically relevant.
Differential Diagnosis
As a result of destructive epithelial changes, epithelial regeneration occurs in various infl ammatory conditions, which affects both the
ectocervical and the metaplastic squamous epithelium. This epithelial regeneration occurs alongside with a regenerative atypia that should not be
mistaken for squamous intraepithelial lesions
(SILs) or neoplastic lesions. Also, one has to
bear in mind that normally, scattered lymphocytes
are present within cervical stroma and have no
clinical significance. A diagnosis of chronic cervicitis should be reserved only for cases where the
presence of inflammatory infi
with clinical symptoms. Sometimes, the presence
of massive inflammatory infiltrate in association
with lymphoid follicles may produce a
lymphoma-like lesion, difficult to differentiate
from a malignant lymphoma. Malignant lymphomas however are rare primary lesions in the cervix
and are associated with a mass. Laboratory investigations together with ancillary immunohistochemical stains may help for a definitive
diagnosis. Also, in case of tuberculous cervicitis
with noncaseating granulomas, other conditions
in which granulomatous nodules may develop
have to be ruled out, such as lymphogranuloma
venereum, sarcoidosis, foreign body giant-cell
granulomas, and schistosomiasis (Ziehl–Neelsen
stain or culture are of help in diagnosing tuberculosis with culture being more sensitive than special stains). Vesicular and bullous cervical lesions
have been described such as pemphigus vulgaris,
ltrate is associated
B
40 Benign Epithelial Tumors and Tumor-Like Lesions, Pathology of the Cervix
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but microscopically, there are multiple
intraepithelial bullae in a suprabasal location
containing characteristic acantholytic Tzanck
cells.
Lobular Endocervical Glandular
Hyperplasia
Synonyms
Florid endocervical glandular hyperplasia with
pyloric and intestinal metaplasia.
Definition
Lobular endocervical glandular hyperplasia
(LEGH) is a proliferation of endocervical glands
with pyloric differentiation. It may be associated
with other mucinous lesions of the female genital
tract, in patients with Peutz-Jeghers syndrome
(germline STK11 mutation) (Kato et al. 2011).
Atypical LEGH is a variant of LEGH with similar
morphology but in association with cellular
atypia.
Clinical Features
• Incidence
This is a rare lesion, more frequently occurring
in Eastern population.
• Age
It involves patients in reproductive age.
• Sex
Female.
• Site
LEGH develops in the upper endocervix.
• Treatment
Surgical excision (with negative margins in
case of atypical LEGH) is recommended.
• Outcome
LEGH is a benign lesion; however, there is
enough information that atypical LEGH, harboring GNAS, KRAS, ST K11 mutations, is a
precursor lesion of HPV-independent gastric
adenocarcinoma (Matsubara et al. 2014). Colposcopy, repeat smears, and imaging of female
genital tract, given risk of gastric-type lesions
elsewhere, are recommended for follow-up in
case of LEGH and especially atypical LEGH.
Benign Epithelial Tumors and Tumor-Like Lesions,
Pathology of the Cervix, Fig. 19 Lobular endocervical
glandular hyperplasia: the lesion is confined to the inner
half of the cervical wall and is characterized by a central
dilated duct-like gland, surrounded by a proliferation of
small glands, with a lobular architecture
Macroscopy
It is either an incidental finding (patients are
asymptomatic) or forms a mass, in which case, it
may be associated with abdominal discomfort and
mucoid or watery discharge.
Microscopy
The lesion is confined to the inner half of the
cervical wall. LEGH is characterized by a central
dilated duct-like gland, surrounded by a proliferation of small glands, with a lobular architecture
(Fig. 19). All structures are lined by a columnar
mucinous epithelium, with cells presenting pale
eosinophilic cytoplasm and basally located nuclei
(Fig. 20). Atypical LEGH is characterized by the
presence of nuclear pleomorphism and hyperchromasia, distinct nucleoli, coarse chromatin,
and occasional mitotic figures and apoptotic bodies. Atypical LEGH also presents with a stratified
epithelium lining the glands, in association with
loss of polarity and forming tufts or papillae.
Stromal desmoplasia is absent in both LEGH
and atypical LEGH. Both lesions contain neutral
mucin (positive for Alcian blue/PAS combination), similar to gastric foveolar epithelium but
not acidic mucin, normally present in endocervical epithelium. On rare occasions, intestinal
metaplasia can occur.
Benign Epithelial Tumors and Tumor-Like Lesions, Pathology of the Cervix 41
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with large amount of cytoplasm, sometimes
containing microvacuoles, basally located
nuclei, subtle cytologic atypia, variable prominent nucleoli, less nuclear stratificat io n and
crowding, and few mitotic figures. Of interest,
atypical LEGH and gastric type of in situ adenocarcinoma are related entities and both
represent precursors of gastric-type invasive adenocarcinoma of the cervix (Stolnicu et al. 2020).
Other types of endocervical hyperplasia
(microglandular hyperplasia, diffuse laminar
hyperplasia, tunnel clusters) all lack the gastric
morphology, characteristic of LEGH.
Benign Epithelial Tumors and Tumor-Like Lesions,
Pathology of the Cervix, Fig. 20 Lobular endocervical
glandular hyperplasia: all structures are lined by a columnar mucinous epithelium, with cells presenting pale eosinophilic cytoplasm and basally located nuclei
Mesonephric Remnants and Hyperplasia
of the Uterine Cervix
B
Immunophenotype
LEGH stains at least positive for HIK1083 and
MUC6 (with HIK1083 being more specific, but
only available in Japan while MUC 6 being less
specific, also positive in normal endocervical epithelium and other premalignant and malignant
lesions) and negative for estrogen receptors
(ERs), progesterone receptors (PRs), and p16
(patchy). P53 mutation can occur in some lesions.
Human papillomavirus (HPV) test is negative.
Molecular Features
Not clinically relevant.
Differential Diagnosis
Minimal deviation adenocarcinoma (gastric-type
invasive endocervical adenocarcinoma, HPVindependent tumor) does not have a lobular
architecture but usually presents bland looking
glands, with minimal atypia, infiltrating throughout the cervical wall and associated with stromal
desmoplasia. Of interest, minimal deviation
adenocarcinoma can harbor areas of LEGH or
atypical LEGH at the periphery of the tumor.
Gastric-type in situ adenocarcinoma has been
recently described as an HPV-independent
lesion, rarely found in Western population, but
lacking a lobular morphology and being
represented by glands lined by epithelial cells,
Definition
Mesonephric remnants represent vestigial remnants of the Wolffian duct while mesonephric
hyperplasia is a benign proliferation of mesonephric remnants.
Clinical Features
• Incidence
Mesonephric remn ants occur in up to 30% of
adult cervices, especially in surgical specimens
such as cone or hysterectomy and in up to 40%
of cervices in newborns and children,
depending on how extensively the speci men
is sampled (Sneeden 1958). Mesonephric
hyperplasia is a rare lesion.
• Age
Any age can be involved for Mesonephric
remnants can occur at any age, but they are
more frequently diagnosed in newborns and
chilfren. Mesonephric hyperplasia on the
other hand occurs more often in reproductive
age or postmenopausal.
• Sex
Female.
• Site
It involves the deep and lateral porti on of the
cervix (3 o’clock and 9 o’clock) but may sometimes be found in the superficial area, beneath
the mucosa.
42 Benign Epithelial Tumors and Tumor-Like Lesions, Pathology of the Cervix
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• Treatment
No treatment is recommended for mesonephric
remnants as for mesonephric hyperplasia, surgical excision is curative.
• Outcome
Excellent for mesonephric remnants. However,
one has to keep in mind that primary mesonephric adenocarcinoma of the cervix rarely
occurs and even a precursor lesion has not
been yet described, mesonephric carcinoma
have been found contiguous with mesonephric
hyperplasia.
Macroscopy
Mesonephric remnants is an incidental
finding, being small (no visible lesion) and
asymptomatic. Mesonephric hyperplasia, however,
may produce thickeningof the mucosa or a cervical
mass, with a variable diameter (5-20 mm).
Microscopy
Mesonephric remnants are characterized by
small tubular glands, clustered in lobules or
presenting with a linear array, often surrounding
a main branching duct (Fig . 21). All structures
are lined by a single non ciliated cuboidal layer
of cells and a prominent basal membrane
(Fig. 22). The lumen of glands presents an
eosinophilic (colloid-like secretion) material,
devoid of mucin (negative for mucicarmin but
positive for PAS). The cuboidal cells have scant
eosinophilic cytoplasm, free of mucin or glycogen (negative for mu cicarmin or PAS). The
nuclei are bland and round, and mitotic activity
is absent or rare. When the lesion is more extensive, with a size of more than 5-6 mm in diameter, it is diagnosed as mesonephric hyperplasia,
but this cut-off is arbitrary (Ferry and Scully
1990). In mesonephric hyperplasia, the tubules
have the same morphologic appearance, but
they are more numerous, crowded, and ma y
sometimes extend in the full thickness of cervical wall and into the lower uterine segment.
Architecturally, the tubules form lobular structures but may also be diffuse. The histological
subclassification of mesonephric hyperplasia
into lobular, diffuse, and d uctal subtype has no
clinical relevance. Stromal desmoplasia is
Benign Epithelial Tumors and Tumor-Like Lesions,
Pathology of the Cervix, Fig. 21 Mesonephric rem-
nants: small tubular glands, presenting with a linear array,
surrounding a main branching duct
Benign Epithelial Tumors and Tumor-Like Lesions,
Pathology of the Cervix, Fig. 22 Mesonephric rem-
nants: all structures are lined by a single nonciliated cuboidal layer of cells and a prominent basal membrane
absent as well as atypia and mitotic numerous
figures. Even in florid lesions, in which not only
the structures are transmural and numerous but
also their shape may be distorted, a careful
search will find small round mesonephric
tubules at the periphery of mesonephric hyperplasia (Figs. 23 and 24).
Immunophenotype
The cells lining the tubules are positive for PAX8,
GATA3, TFF1, CD10, and Calretinin and negative
for estrogen receptors (ERs) and progesterone
receptors (PRs). P16 is negative (patchy) and p53
is wild type.
Benign Epithelial Tumors and Tumor-Like Lesions, Pathology of the Cervix 43
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with immunohistochemical stains can assist.
Also, mesonephric hyperplasia can mimic
mesonephric or endometrioid subtype of cervical invasive adenocarcinoma. Primary mesonephric adenocarcinoma of the cervix is a very
rare, human papillomavirus (HPV)-independent
tumor, associated with a tumor mass and in
which atypia (many nuclei may be oval, optically clear, grooved, and overla pping, similar to
papillary thyroid carcinoma), mitotic activity,
desmoplastic stroma, lympho-vascular invasion
and spread outside the cervix are present. Also,
architecturally, these tumors characteristically
Benign Epithelial Tumors and Tumor-Like Lesions,
Pathology of the Cervix, Fig. 23 Florid mesonephric
hyperplasia: the structures are transmural and numerous
but a careful search will find small round mesonephric
remnants at the periphery of mesonephric hyperplasia
exhibit an admixture of growth patterns, including ductal, tubular, glomeruloid, papillary,
retiform, solid, sex cord-like, and spindled
(sarcomatoid). The tumor usually develops in
the lateral aspect of the cervix, but when discovered, there is usually circumferential cervical
involvement. Endometrioid subtype adenocarcinoma of the cervix is also a rare, HPVindependent tumor, with endometrioid-type
morphology and usually positive for ERs, PRs,
and v imentin while GATA3 is negative
(Tambouret et al. 2003). Mesonephric hyperp lasia can also overlap morphologically with tunnel clusters and lobular endocer vical glandular
hyperplasia, but immunohistochemistry can
help as these two ben ign endocervical lesions
are negative for GATA3 and CD10 and in addition, tunnel clusters are also positive for ERs
Benign Epithelial Tumors and Tumor-Like Lesions,
Pathology of the Cervix, Fig. 24 Florid mesonephric
hyperplasia: the structures have a distorted shape but are
lined by a single nonciliated cuboidal layer of cells and a
prominent basal membrane, while luminal eosinophilic
colloid-like content can be appreciated
and PRs.
Microglandular Hyperplasia of the
Uterine Cervix
B
Molecular Features
Studies have shown that KRAS and NRAS mutations (frequently found in mesonephric adenocarcinoma) are absent in mesonephric hyperplasia
(Mirkovic et al. 2017).
Differential Diagnosis
Main differential for superficially located mesonephric remnants is with cervical adenocarcinoma (in situ or invasive) b ut lack of stromal
desmoplasia, atypia, mitotic figures together
Definition
A benign, non-neoplastic proliferation of endocervical glands, lined by mucinous epithelium,
occurring in association with hormonal influence
or developed as a reparative process.
Clinical Features
• Incidence
Frequently detected as an incidental finding
(up to 27%) on a cervical biopsy, cone biopsy,
or a hysterectomy specimen.
44 Benign Epithelial Tumors and Tumor-Like Lesions, Pathology of the Cervix
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• Age
Most often occurs in reproductive-age women,
during pregnancy or related to oral contraceptive use but may also involve postmenopausal
patients, taking hormonal replacement therapy
(Gondos 1976; Wilkinson and Dufour 1976).
Cases in which the lesion is not associated with
hormonal influence have also been described.
• Sex
Female.
• Site
The lesion develops at the transformation zone,
involving the surface epithelium but also
deeper endocervical glands. It can also occur
in the upper endocervical canal.
Benign Epithelial Tumors and Tumor-Like Lesions,
Pathology of the Cervix, Fig. 25 Microglandular
hyperplasia: closely packed, proliferation of small glands
• Treatment
Surgical excision is only recommended for
large polypoid lesions.
• Outcome
Excellent.
Macroscopy
Small lesions can be found only at microscopic
examination or presenting as a cervical erosion
but larger lesions (1–2 cm in size) are often polypoid, sessile, or pedunculated and can be associated with postcoital bleeding. Microglandular
hyperplasia can be detected as a unifocal or multifocal lesion.
Microscopy
At microscopic examination, there is a closely
packed, proliferation of small glands, lined by a
single layer of cuboidal/columnar/flat epithelial
cells, surrounded by a basal cell layer (Fig. 25).
Glands are arranged in a lobular configuration and
surrounded by little intervening stroma (Fig. 26).
The epithelial cells present clear to finely granular
eosinophilic cytoplasm, with variable amount of
mucin and subnuclear vacuolization. The nuclei
are uniform, small, and round, with fine chromatin, while mitotic figures are rare or absent. Glandular lume ns contain variable amount of mucin
and neutrophils (Figs. 27 and 28). Epithelial cells
and intraglandular mucin stain with mucicarmin,
Alcian blue, and periodic acid-Schiff (PAS) with
diastase digestion. Also, inflammatory infiltrate,
stromal edema , and foci of squamous metaplasia
Benign Epithelial Tumors and Tumor-Like Lesions,
Pathology of the Cervix, Fig. 26 Microglandular
hyperplasia: glands are arranged in a lobular configuration
and surrounded by little intervening stroma
canbeidentified throughout the lesion. Of inter-
est, areas of squamous metaplasia can be involved
by squamous intraepithelial lesion (SIL). Unusual
forms of microglandular hyperplasia have been
described, presenting with solid, cribriform, reticular or cystic architecture, extensive areas of
hyalinization, pools of mucin with detached
islands of cells, basal (reserve) cell hyperplasia,
spindle-shaped cells, polygonal cells with abundant eosinophilic cytoplasm, or signet-ring
cells. Very rarely, microglandular hyperplasia displays areas of cytologic atypia and a higher
mitotic ind ex (Abi-Raad et al. 2014) (Figs. 29
and 30).
Benign Epithelial Tumors and Tumor-Like Lesions, Pathology of the Cervix 45
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B
Benign Epithelial Tumors and Tumor-Like Lesions,
Pathology of the Cervix, Fig. 27 Microglandular
hyperplasia: glands are lined by a single layer of cuboidal/columnar/flat epithelial cells, surrounded by a basal cell
layer
Benign Epithelial Tumors and Tumor-Like Lesions,
Pathology of the Cervix, Fig. 28 Microglandular
hyperplasia: glandular lumens contain variable amount of
mucin and neutrophils
Immunophenotype
Estrogen receptors (ERs) are positive within epithelial cells as well as PAX2 and cyclin D, while
progesterone receptors (PRs), p16 (patchy, mosaic
type), CEA, and vimentin are negative. p63 is
positive in the basal cell layer, surrounding most
glands. Caution must be taken when interpreting
this marker as in some lesions, the basal cell layer
can be attenuated or focally absent. Ki-67 index is
generally low.
Molecular Features
Not clinically relevant.
Benign Epithelial Tumors and Tumor-Like Lesions,
Pathology of the Cervix, Fig. 29 Microglandular
hyperplasia: sometimes the lesion is extensive
Benign Epithelial Tumors and Tumor-Like Lesions,
Pathology of the Cervix, Fig. 30 Microglandular
hyperplasia with a polypoid appearance
Differential Diagnosis
Microglandular hyperplasia must be distinguished
from clear cell adenocarcinoma of the cervix or
endometrium, especially in a small biopsy. Features in keeping with a diagnosis of clear cell
adenocarcinoma are patient’s history, clinical
symptoms, macroscopic features (tumor is
forming a mass) together with the presence of
atypical tumor cells (enlarged and hyperchromatic
nuclei), hobnail cells, mitotic figures, and absence
of reserve cells and squamous metaplasia. Also,
microglandular hyperplasia must be differentiated
from endometrial endometrioid adenocarcinoma
with mucinous differentiation, sometimes presenting with a microglandular architecture
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