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Mucinous Tumors, Pathology of the Ovary 329
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Mucinous Tumors, Pathology of the Ovary, Table 2 The list of morphological features of primary and metastatic
ovarian carcinomas
Favor primary Favor metastatic Unhelpful features
Smooth capsule Involvement of the surface and superficial cortex Gross cysts
Evenly distributed cystic and
solid areas (no discrete
nodularity)
Areas of MBT and/or mucinous
cystadenoma
Expansile invasion Infiltrative (destructive) invasion Pseudomyxoma
Complex papillary pattern Bilaterality Cribriform, villous,
Size > 10 cm (>15 cm) Hilar involvement Goblet cells
Associated teratoma or Brenner
tumor
Microscopic cystic glands Signet ring cells Focal areas
Mural nodule Vascular invasion
Unilateral Microscopic mucus on the surface
Low stage Pseudomyxoma peritonei
Younger patients Intraperitoneal spread
Nodular pattern (gross and/or microscopic), including
gross mucinous multinodular appearance
Areas of MBT and/or mucinous cystadenoma less
frequent, commonly associated with high-grade nuclear
atypia
Single cell invasion Tumor grade
Colloid morphology
Established history of cancer
Gross solid,
papillary,
hemorrhagic areas
Nature of the content
of the cysts
ovarii
or solid growth
resembling colonic
carcinoma
M
tumor is 99.7%, but primary ovarian MC can
rarely show this component as well
(McCluggage & Young, 2008). Moreover, the
sensitivity of this morphology for metastatic origin of the tumor is low (approximately 12%).
Another feature which is highly specific for metastatic tumors is the presence of pseudomyxoma
peritonei (PMP). However, some ovarian mucinous tumors arising in a teratoma can be associated
with PMP, and this feature is also not entirely
specific (Ronnett & Seidman, 2003). Similarly, a
feature suggestive of primary ovarian MC is the
presence of areas with benign and/or borderline
appearance, but these areas can also be encountered in metastatic tumors, especially from the
pancreas or pancreatobiliary tract (Young &
Hart, 1989; Young & Scully, 1991). Rarely,
these areas can be the only morphologic pattern
in metastatic tumors.
Despite being helpful, the diagnosis cannot be
achieved with certainty based only on these features in all cases. In these equivocal cases, the use
of immunohistochemical methods seems to be a
suitable approach. Although these methods play
an important role in the differential diagnosis
between primary and metastatic mucinous ovarian
tumors, their importance in tumors originating
from GIT especially is limited, mostly due to the
overlapping immunophenotype. As a result of
that, another algorithmic approach to the differential diagnosis of these tumors has been proposed.
The idea of this approach is based on the fact that
some macroscopic and microscopic features are
different between primary and metastatic tumors.
The most common approach is based on the combination of size and laterality, with the assumption
that the primary ovarian mucinous tumors are
large (most used cut-offs are 10, 12, 13 or
15 cm) and unilateral. Some algorithms also consider other features, such as age or immunohistochemical markers (PAX8 or DPEP1). How ever,
despite being helpful, algorithms on their own are
not sufficient in distinguishing between primary
and secondary tumors as even metastatic tumors
330 Mucinous Tumors, Pathology of the Ovary
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may be large and unilateral, and primary tumors
may be small and bilateral. The mean accuracy of
algorithms in distinguishing between primary and
metastatic tumors is about 83%, with sensitivity
for the identification of primary tumors reaching
approximately 82% and specificity 83%.
According to current knowledge, the most
reliable approach for the diagnosis of ovarian
mucinous tumors, especially MC, is based on
the assessment of all features including macroscopic, microscopic, immunohistochemical
(if needed), and close clinico-pathological correlation. Nevertheless, rare tumors remain equivocal, and in these cases, a close follow-up of the
patient is crucial.
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W. Y., & Lu, X. (2020). Mucinous borderline ovarian
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ferences in clinicopathologic features and fertility
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problematics. Diagnostic Pathology, 16(1), 20. https://
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Drozenova, J., et al. (2023a). Primary mucinous tumors
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Neuroectodermal Tumors,
Pathology of the Vulva
Evi Abada
Department of Pathology, Wayne State University
School of Medicine, Detroit, MI, USA
Synonyms
Extraosseous/extraskeletal Ewing sarcoma; Primitive neuroectodermal tumors (PNET).
Definition
Primitive neuroectodermal tumors (PNETs) represents a biologically aggressi ve, poorly dif ferentiated
malignant neoplasm that demonstrates cellular differentiation that recapitulates cell typesof the central
nervous system (CNS) (Chiang et al., 2017). The
entity has been grouped into two major categories,
namely , those that mimic neoplasms of the CNS,
i.e., central PNET, and those composed of small
round cells with or without rosettes known as extraosseous/extraskeletal Ewing sarcoma (ES) or
peripheral PNET (Chiang et al. 20 17). Extraosseous
ES/PNETs of the female genital tract are very
unusual and only rare cases arising from the vulva,
vagina, uterine corpus, and ovaries have been
reported (Fong et al. 2008). However, to date,
none have been reported to have arisen in the
fallopian tube (Chiang et al. 2017).
Clinical Features
• Incidence and Age
A recent review from 1960 to July 2020
documents that the majority of patients with
extraosseous ES/PNET are young with most
patients being less than 30 years, while the
youngest was 3 years old and the oldest was
87 years old (Tintila et al. 2021). The clinical
findings in vulvar PNET or extraosseous ES
vary from the presence of a rapidly growing
tumor to a cystic or peduncled appearance on
the labia majora, labia minora, or clitoris, or to
the presence of ulceration or inguinal lymphadenopathy (Tintila et al. 2021).
• Sex
Female.
• Site
Extraosseous ES/PNETs of the female genital
tract are very unusual and only rare cases arising from the vulva, vagina, uterine corpus, and
ovaries have been reported (Fong et al. 2008).
However, to date, none have been reported to
have arisen in the fallopian tube (Chiang et al.
2017).
• Treatment
Given the rarity of cases, there are no guidelines for the treatment of these types of tumors.
The treatments are often multimodal,
depending on the location, extent, and characteristics of the tumors. The recommended treatments include surgery, radiotherapy, and
systemic chemotherapy (Tintila et al. 2021).
© Springer Nature Switzerland AG 2023
S. Stolnicu, R. Ali-Fehmi (eds.), Gynecologic Pathology, Encyclopedia of Pathology,
https://doi.org/10.1007/978-3-030-97378-0
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Chemotherapy may be neoadjuvant, adjuvant,
or palliative. However, when feasible, surgery
is always recommended first. Adjuvant chemo-
therapy has demonstrated significant survival
benefit. The main chemotherapeutic agents
used in the treatment of PNET and extra-
osseous ES are those that are also used for ES
of the bone (Tintila et al. 2021).
• Outcome
There is very limited information available
regarding the prognosis of primary ES/PNET of
the vulva; however, it appears that these tumors
may be associated with a better prognosis than
other extraosseous ES/PNET of the female gen-
ital tract and soft tissue (F ong et al. 2008).
Neuroectodermal Tumors, Pathology of the Vulva,
Fig. 1 PNET. Hematoxylin and eosin section showing a
diffuse proliferation of small round blue cells, with focal
areas showing vague pseudorosette formations
Microscopy
Histologically, these tumors are characterized
either by a small round cell proliferation (Fig. 1)
or by a variable degree of neuronal or glial differentiation (Chiang and Young 2020). They are
composed of sheets or nodules of densely packed
primitive cells with small- to medium-sized,
round to ovoid nuclei, oneto multiple small nucleoli, scant cytoplasm, and numerous mitoses (>10/
10 high power fields) (Chiang et al. 2017) (Fig. 2).
Immunohistochemically, they show membranous
CD99 and nuclear FLI1 expression, and are often
positive for CD56, NSE, and synaptophysin
(Chiang and Young 2020). They are rarely positive for broad-spectrum cytokeratin, and they are
negative for desmin (Chiang et al. 2017 and
Murdock et al. 2018). About 50% of tumors
(most commonly differentiated ones) express
GFAP (Chiang et al. 2017).
Neuroectodermal Tumors, Pathology of the Vulva,
Fig. 2 PNET. Hematoxylin and eosin section showing
sheets of primitive-type cells with small- to mediumsized, round to ovoid nuclei, scant cytoplasm, and one to
multiple nuclei. Some mitotic figures are also evident in
this field
Molecular Features
From a molecular perspective, PNET and extraosseous ES exhibit the chromosomal abnormality
t(11;22)(q24;q12), which involves the binding of
the EWSR1 gene with the FLI1 gene, which
encodes the EWS/FLI fusion protein. This translocation is essential to confirm the diagnosis of
rare tumors, including PNETand extraosseous ES
of the vulva or vagina (Tintila et al. 2021).
Differential Diagnosis
Before a diagnosis of PNET or extraosseous ES of
the vulvar is made, other diagnoses must be
excluded including genital herpes, inguinal granuloma caused by Klebsiella granulomatis,chancroid
due to Haemophilus ducreyi, rhabdomyosarcoma,
malignant fibrous histiocytoma, leiomyosarcoma,
epithelioid sarcoma, neuroblastoma, Paget’sdisease
of the vulva, lymphoma, small cell carcinoma,
malignant melanoma (~10% of vulvar tumors),
Merkel cell carcinoma, squamous cell carcinoma
Neuroendocrine Tumors, Pathology of the Cervix 335
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of the vulva, Bartholin’s gland cyst, Bartholin’s
gland carcinoma, basal cell carcinoma of the
vulva, vulvar wart carcinoma, and metastases from
other organs (T in tila et al. 2021).
References
Chiang, S., & Young, R. H. (2020). Neuroectodermal-type
tumours. In The WHO Classification of Tumours Edi-
torial Board (Ed.), Female Genital Tumours (Vol. 4,
5th ed., p. 136). Lyon.
Chiang, S., Snuderl, M., Kojiro-Sanada, S., Quer Pi-Sunyer,
A., Daya, D., Hayashi, T., Bosincu, L., Ogawa, F.,
Rosenberg, A. E., Horn, L. C., Wang, L., Iafrate, A. J.,
& Oliva, E. (2017). Primitiveneuroectodermal tumors of
the female genital tract: A morphologic, immunohisto-
chemical, and molecular study of 19 cases. The Ameri-
can Journal of Surgical Pathology, 41(6), 761–772.
https://doi.org/10.1097/PAS.0000000000000831.
Fong, Y .E., López-Terrada, D., & Zhai,Q. J.(2008). Primary
Ewing sarcoma/peripheral primitive neuroectodermal
tumorofthevulva.Human Pathology, 39(10),
1535–1539. https://doi.org/10.1016/j.humpath.2008.
01.013.
Murdock, T., Orr, B., Allen, S., Ibrahim, J., Sharma, R.,
Ronnett, B. M., & Rodriguez, F. J. (2018). Central ner-
vous system-type neuroepithelial tumors and tumor-like
proliferations developing in the gynecologic tract and
pelvis: clinicopathologic analysis of 23 cases. The Amer-
ican Journal of Surgical Pathology, 42(11), 1429–1444.
https://doi.org/10.1097/PAS.0000000000001131.
Tintila, A., Doroftei, B., Grab, D., Simionescu, G., Anton,
E., Maftei, R., Ilea, C., & Anton, C. (2021). Importance
of studying primitive neuroectodermal tumors and
extraosseous Ewings sarcoma of the vagina and
vulva. Oncology Letters, 21(2), 171. https://doi.org/
10.3892/ol.2021.12432.
Neuroendocrine Tumors,
Pathology of the Cervix
Noorah Almadani2and Lynn Hoang
1
Anatomical Pathology, Vancouver General
Hospital, Vancouver, BC, Canada
2
University of British Columbia, Vancouver, BC,
Canada
Definition
These tumors are through to arise from embryonic
neural crest cells and thus exhibit neuroendocrine
1,2
differentiation. The World Health Organization
5th Edition separates these tumors into two main
categories: well-differentiated neuroendocrine
tumors (NETs) and poorly differentiated neuroendocrine carcinomas (NECs). NET captures lowgrade and intermediate grade tumors (also called
carcinoid and atypical carcinoid tumors). NEC
captures small cell neuroendocrine carcinoma
(SCNEC) and large cell neuroendocrine carcinomas (LCNEC) (WHO 2020).
In comparison to other gynecological organs,
the uterine cervix is the most common site of
occurrence for NEC (Chun 2015). Like other cervical cancers, NEC appears to be associated with
high-risk human papillomavirus (HPV) infection
(Siriaunkgul et al. 2011). NEC can be mixed
with various non-neuroendocrine tumors, such
as squamous cell carcinoma, HPV-associated
invasive adenocarcinoma, and mesonephric
carcinoma.
Clinical Features
• Incidence
Primary neuroendocrine neoplasms in the cer-
vix comprise less than 5% of cervical tumors
(Margolis et al. 2016). Of all neuroendocrine
tumors, small cell neuroendocrine carcinoma is
the most common type to occur, whereas typ-
ical carcinoid (NET grade 1) and atypical car-
cinoid (NET grade 2) are very rare (Lax
et al. 2016).
• Age
Cervical neuroendocrine tumors have been
reported in a wide age range (22–87 years
old), the median age is 45 years old (Margolis
et al. 2016).
• Site
The most common site is the cervix. However,
neuroendocrine tumors can occur at any site in
the female genital tract and body.
• Treatment
Given that cervical NEC are uncommon, treat-
ment guidelines are often inferred from other
sites (Margolis et al. 2016). Surgery for tumors
4 cm combined with adjuvant chemotherapy
is common for early FIGO stage disease,
whereas advanced stage disease is treated with
N
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combination chemotherapy and radiation. Cisplatin and etoposide or vincristine, doxorubicin,
and cyclophosphamide are the most common
chemotherapy regimens. NEC are more likely
to benefit from adjuvant chemotherapy and
radiotherapy in comparison to cervical squamous cell carcinoma and adenocarcinoma
(Margolis et al. 2016). The Society of Gyneco-
logic Oncology (SGO) recommends that welldifferentiated neuroendocrine tumors be managed similar to gastrointestinal and pancreatic
NET (Gardner et al. 2011). The Gynecologic
Cancer InterGroup (GCIG) guidelines for NEC
suggest surgery accompanied with neoadjuvant
or adjuvant therapy for operable tumors, and
chemoradiation or systemic chemotherapy for
inoperable tumors (Satoh et al. 2014).
• Outcome
NECs are well known of their aggressive behavior in any organ in the body, including the uterine
cervix. At the time of initial diagnosis, it is rarely
localized and has a propensity to invade locally
andspreadtodistantsiteseveninearlystagesof
the disease (Tempfer et al. 2018). The 5-year
survival rates for NEC are reported at 0–30%,
fairing worse than other types of cervical carcinoma. For womenwith early FIGO stage tumors,
5-year survival was only 55% compared to 80%
for patients with squamous cell carcinomas and
86% for adenocarcinomas. For those with
advanced FIGO stage tumors, 5-year survival
rates were 24% and 43%, respectively
(Siriaunkgul et al. 2011). Due to the scarcity of
low grade NET, their biological behavior canno t
be determined (Chun 20 15).
nested, pseudoglandular, rosette-like, or sheetlike architectural patterns. The small, round, and
uniform (monotonous) tumor cells have a finely
granular chromatin pattern and inconspicuous
nucleoli. Mitotic activity is low (Fig. 1). NEC,
including small cell NEC and large cell NEC,
exhibit geographic necrosis, abundant mitoses
(usually more than 10 mitoses per 10 highpower fields) , along with loss of organoid architecture that is usually observed in low-grade NET
(Albores-Saavedra et al. 1997). Small cell NEC
frequently exhibits poorly defined sheets of
loosely cohesive cell s with high nuclear/cytoplasmic ratios, scanty cytoplasm, nuclear hyperchromasia, nuclear molding, apoptosis amid
variable hemorrhage (Fig. 2). Large cell NEC
Neuroendocrine Tumors, Pathology of the Cervix,
Fig. 1 Neuroendocrine tumor (carcinoid tumor) of the
cervix. There is an insular pattern with pseudoglandular
spaces. The nuclei are monotonous and round, with scant
mitotic figures
Macroscopy
The macroscopic features range from small and
inobtrusive lesions to large ulcerating exophytic
nodules that may replace the cervix and involve
adjacent organs.
Microscopy
Neuroendocrine tumors (carcinoid and atypical
carcinoid) show trabecular, ribbon-like, insular,
Neuroendocrine Tumors, Pathology of the Cervix,
Fig. 2 Small cell neuroendocrine carcinoma of the cervix.
The cells have a high N:C ratio with minimal cytoplasm.
The nuclei are hyperchromatic and show nuclear molding.
Brisk mitotic activity and apoptotic debris are seen
Neuroendocrine Tumors, Pathology of the Cervix 337
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exhibit ample eosin ophilic cytoplasm with conspicuous nucleoli (Fig. 3) (Rekhi et al. 2013).
NEC is likely to show lymphovascular space
invasion and regional lymph node metastasis.
Immunophenotype
These tumors are almost all HPV-associated and
stain strong/diffuse with p16 (McCluggage et al.
2010). The predominant subtypes are HPV18 and
HPV16 (Figs. 4 and 5) (Castle et al. 2018).
Immunohistochemistry is crucial to make the
diagnosis as NET/NEC can be mistaken for highgrade endometrial or endocervical adenocarcinoma
(Chun 2015). Synaptophysin, chromogranin, and
CD56 are the most commonly used, although
CD56 is known to be a less specific (Fig. 6). NSE
is another marker that can be useful. For
establishing the diagnosis, positive staining of at
least two neuroendocrine markers is generally
recommended. For large cell NEC, at least one
neuroendocrine marker is recommended.
Unlike other NET/NEC tumors at other sites in
the body, Ki-67 labeling index is not included in
the diagnostic criteria (Colgan et al. 2013).
Molecular Features
Genetic alterations in the mTOR and PIK3CA/
PTEN/AKT signaling pathways have been
described. These tumors are microsatellite stable
(Cimic et al. 2020; Zhu et al. 2019).
Neuroendocrine Tumors, Pathology of the Cervix,
Fig. 3 Large cell neuroendocrine carcinoma of the cervix.
The moderate to large polyhedral cells are discohesive.
There is moderate eosinophilic cytoplasm and enlarged
nuclei with conspicuous nucleoli
Neuroendocrine Tumors, Pathology of the Cervix,
Fig. 4 Neuroendocrine tumor (right) and high-grade
small cell neuroendocrine carcinoma (left) of the cervix
N
Neuroendocrine Tumors, Pathology of the Cervix,
Fig. 5 Neuroendocrine tumor (right) and high-grade
small cell neuroendocrine carcinoma (left) of the cervix.
p16 is positive (strong and block-like) in both components
Neuroendocrine Tumors, Pathology of the Cervix,
Fig. 6 Neuroendocrine tumor (right) and high-grade
small cell neuroendocrine carcinoma (left) of the cervix.
Synaptophysin is positive in both components
338 Neuroendocrine Tumors, Pathology of the Fallopian Tube
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Differential Diagnosis
Cervical neuroendocrine tumors are rare, therefore, exclusion of primary disease elsewhere in
the body should be done first. The differential
diagnosis of NEC includes metastasis of extracervical NEC (e.g., lung, gastrointestinal, pancreatic, and less commonly urina ry bladder). TTF1
and CDX2 expression does not exclude a primary
cervical NEC. Merkel cell carcinoma of the skin
can be excluded with a combination of CK20
(dot-like staining) and polyomavirus and clinical
history.
NEC can also be confused with lymphomas,
poorly differentiated squamous cell carcinomas,
sarcomas, and melanomas with small cell features
(Tempfer et al. 2018). Large cell NECC may be
positive for p63, a marker strongly expressed in
squamous cell carcinomas. In this scenario, positive immunohistochemical staining for neuroendocrine markers can exclude the diagnosis of
squamous cell carcinoma.
References and Further Reading
Albores-Saavedra, J., et al. (1997). Terminology of endo-
crine tumors of theuterine cervix: results of aworkshop
sponsored by the College of American Pathologists and
the National Cancer Institute. Archives of Pathology &
Laboratory Medicine, 121, 34.
Castle, P. E., Pierz, A., & Stoler, M. H.(2018). A systematic
review and meta-analysis on the attribution of human
papillomavirus (HPV) in neuroendocrine cancers of the
cervix. Gynecologic Oncology, 148,422–429.
Chun, Y. K. (2015). Neuroendocrine tumors of the female
reproductive tract: A literature review, 450–461.
Cimic, A., etal. (2020). Molecular profiling reveals limited
targetable biomarkers in neuroendocrine carcinoma of
the cervix. Applied Immunohistochemistry & Molecu-
lar Morphology. https://doi.org/10.1097/PAI.
0000000000000884.
Colgan, T. J., Hirschowitz, L., Kim, I., et al. (2013). Neu-
roendocrine tumours. WHO Classification of Tumours
of Female Reproductive Organs. Kurman RJ,
Carcangiu ML, Herrington CS, et al. (eds): IARC,
Lyon; 4th Edition:196–8.
Gardner, G. J., Reidy-Lagunes, D., & Gehrig, P. A. (2011).
Neuroendocrine tumors of the gynecologic tract:
A Society of Gynecologic Oncology (SGO) clinical
document. Gynecologic Oncology, 122, 190–198.
Lax, S. F., Horn, L.-C., & Löning, T. (2016). Categori-
zation of uterine cervix tumors: What’s new in the
2014 WHO classificat ion. Der Pathologe, 37(6),
573–584.
Margolis, B., et al. (2016). Natural history and outcome of
neuroendocrine carcinoma of the cervix. Gynecologic
Oncology, 141, 247–254.
McCluggage, W.G., Kennedy, K., & Busam, K.J. (2010).
An immunohistochemical study of cervical neuroendocrine carcinomas: Neoplasms that are commonly
TTF1 positive and which may express CK20 and
P63. The American Journal of Surgical Pathology,
34, 525–532.
Rekhi, B., et al. (2013). Annals of Diagnostic Patholo gy
Spectrum of neuroendocrine carcinomas of the uterine cervix, including histopathologic f eatures, terminology, immunohistochemical profile, and
clinical outcomes in a series of 50 cases from a single
institution in India. Annals of Diagnostic Pathology,
17,1–9.
Satoh, T., et al. (2014). Gynecologic Cancer InterGroup
(GCIG) consensus review for small cell carcinoma of
the cervix. International Journal of Gynecological
Cancer, 24(9 Suppl 3), S102–S108.
Siriaunkgul, S., et al. (2011). HPV genotyping in neuroen-
docrine carcinoma of the uterine cervix in northern
Thailand. International Journal of Gynecology &
Obstetrics, 115, 175–179.
Tempfer, C. B., et al. (2018). Neuroendocrine carcinoma of
the cervix: a systematic review of the literature. BMC
Cancer, 18, 516–530.
WHO classification of tumours of female genital tumours
(5th ed). Lyon: International Agency for Research on
Cancer, 2020.
Zhu, R., Wu, H., Chen, B., Pang, J., & Huo, Z. (2019).
Clinicopathological characteristics and molecular
abnormalities of primary grade 2 neuroendocrine
tumors of the cervix. Diagnostic Pathology, 14,1–8.
Neuroendocrine Tumors,
Pathology of the Fallopian
Tube
Isabel Alvarado-Cabrero
Department of Pathology, Mexican Oncology
Hospital, Mexico City, Mexico
Synonyms
Neuroendocrine tumors or neuroendocrine
neoplasias.
Neuroendocrine Tumors, Pathology of the Fallopian Tube 339
https://t.me/med1917
Historically, well-differentiated neuroendocrine tumors (NET) have been referred to as carcinoid tumors (Oronsky et al. 2017).
High-grade neuroendocrine tumors or neoplasms are referred as carcinomas.
Definition
In current practice, based on clinical behavior,
histology, and proliferative rate, neuroendocrine
tumors (NETs) are generally categorized, similar
to lymphomas, as low-grade indolent tumors
versus high-grade aggressive carcinomas
(Hung 2019).
Clinical Features
• Incidence
Primary neuroendocrine tumors of the
fallopian tube are extremely rare with only a
few case reports in the literature (Grondin et al.
2019). There are occasional reports of high-
grade neuroendocrine carcinoma of the
fallopian tube and one reported case of a
well-differentiated neuroendocrine tumor
associated with a mature cystic teratoma
(Astall et al. 2000; Dursun et al.; 2004;
Raghunath et al. 2010; Neumann et al. 2010;
Crochet et al. 2012; Kim et al. 2015).
• Age
These neoplasms mainly occur in peri- or post-
menopausal women (Crochet et al. 2012).
• Site
Fallopian tube.
• Clinical Presentation
Patients may present with a pelvic mass or
abdominal pain (Neumann et al. 2010; Kim
et al. 2015).
• Treatment
Well-differentiated tumors (“carcinoid
tumors”) can be treated with hysterectomy
and bilateral salpingo-oophorectomy, but a
unilateral salpingo-oophorectomy is suffi-
cient in a young woman (Grondin et al.
2019). Treatment strategies for high-grade
neuroendocrine carcinomas are similar to
those for carcinoma of the ovary (Javellana
et al. 2019).
• Outcome
Well-differentiated tumors tend to have a favorable prognosis; however, this tumor appears
capable of giving rise to metastasis. Highgrade neuroendocrine carcinomas may have a
highly aggressive clinical course (Satoh
et al. 2014).
Macroscopy
Fallopian tube neuroendocrine tumors vary in
size, ranging from small tumors detected only
microscopically to large masses up to 7 cm in
diameter (Crochet et al. 2012).
Microscopy
Well-differentiated neuroendocrine tumors
(NETS) are characteristically arranged in a
well-developed “organoid” or neuroendocrine
shape with nesting, trabecular, or gyriform/serpentine growth patterns. The tumor cells are
small with relative uniform round to oval nuclei,
inconspicuous nucleoli, and fine to coarsely
granular chromatin pattern. In contrast, neuroendocrine carcinomas (NECS) demonstrate a solid
“sheet-like” proliferation of tumor cells with
irregular nuclei, high mitotic features, and less
cytoplasmic secretory granules (Fig. 1) (Oronsky
et al. 2017).
Immunophenotype
Well-differentiated neuroendocrine tumors show
an intense and diffuse immunoexpression of
chromogranin and synaptophysin. On the other
hand, immunohistochemical staining patterns for
neuroendocrine carcinomas markers are more
limited (diffuse expression of synaptophysin,
faint or focal staining for chromogranin) (Fig. 2)
(Dursun et al. 2004).
N
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