2. INTRODUCTION
NEUROENDOCRINE TUMOR-
ZEBRA’S OF ONCOLOGY WORLD.
If we hear hoofbeats, what animal would we think of? A horse, is the
most obvious answer.
Unfortunately, in the medical world, not all diagnoses are horses or the
most likely possibility, and sometimes physicians need to look for the
zebra — the less likely scenario when making a diagnosis.
10th of nov-world neuroendocrine awareness day.
November-Carcinoid tumor awareness month
4. • NETs comprises of ~2% of all malignancies
• The term “ neuroendocrine” is applied to widely dispersed cells with
“ neuro ” and “ endocrine ” properties.
• The “ neuro ” property is based on the identification of DCGs that
are similar to DCGs present in serotonergic neurons,which store
monoamines.
• The “ endocrine ” property refers to the synthesis and secretion of
these monoamines.
5. • For functional purposes,NENs are divided into two groups
well differentiated(low grade to intermediate grade)NETs
poorly differentiated(highgrade)NETs
• NETs have got a body-wide distribution of NEcells-
CNS,respiratory tract,the larynx,GIT,thyroid,skin,breast,and
urogenital system.
• GIT (62-67%)and lungs(22-27%) are the most common primary
tumor sites.
• Most NENs arise sporadically, but association with the multiple
endocrine neoplasia type 1 syndrome and familial clustering is
recognized.
(Bosmanetal.,2010)
6. • The clinical rule of thumb (with exceptions) is that low-grade
tumors are managed with surgical resection while unresectable and
symptomatic disease is treated with somatostatin analogs or interferon-
α even though tumor regression with these agents is
rare.
• In contrast, etoposide/platinum-based chemotherapy is the
mainstay of treatment for high-grade or metastatic neuroendocrine
carcinomas ; however, other agents and modalities are underactive
investigation.
• They include targeted agents like sunitinib and everolimus and the
experimental epi-immunologic agent, RRx-001, as well as evolving
modalities like peptide receptor targeted therapies and
radioembolization.
9. NEC OF CERVIX
• Neuroendocrine tumors are a rare entity of
the female genital tract, with cervix being
the most common primary site.
• First described by Albores-Saavedra in
1972, these tumors account for 1.4% of all
invasive cervical cancers.
10. • The first description of small cell endocrine
carcinoma of the cervix was made in 1957
12. GRADING OF NET
OF CERVIX
Well-differentiated
NENs include neuroendocrine tumors
(NET) G1 (typical carcinoid),
NET G2 (atypical carcinoid), and
NET G3.
Poorly differentiated (NECs) include
small cell NEC and
large cell NEC
Neuroendocrine carcinoma of the cervix: a
systematic review of the literature2018
Clemens B. Tempfer1*, Iris Tischoff2Askin
Dogan1Ziad Hilal1Beate Schultheis3
, Peter Kern4and Günther A. Rezniczek
13. ETIOLOGY
• NEC of cervix is HPV associated(esp HPV 16
& 18)
• HPV 18>HPV16
• marked lymphatic permeation, a feature that
is particularly characteristic of HPV18-related
tumors
• All carcinoid, atypical carcinoid, and large-cell
NEC were p16-positive, while 79% of small-
cell carcinomas showed p16positive staining
1.Alejo M, Alemany L, Clavero O, et al. Contribution of human papillomavirus in neuroendocrine tumors from a
series of 10,575 invasive cervical cancer cases. Papillomavirus Res 2018;5:134–42.
2. Lai C-H, Chang C-J, Huang H-J, et al. Role of human papillomavirus genotype in prognosis of early-stage
cervical cancer undergoing primary surgery. JCO 2007;25:3628–34.
14. • Because NEC of the cervix is uncommon, the etiology and predisposing risk
factors are poorly understood.
• women were slightly younger at the time of diagnosis. The mean age at diagnosis
was 49 years-old .
• There was also a higher proportion of Asian women with NEC of the cervix,
when compared to women with squamous cell carcinoma of the cervix
• While smoking Is a risk factor for developing most other kinds of cervical cancer,
less is known about the role they play in development NEC of the cervix.
• unlike HPV-associated SCC of the cervix which have a preinvasive lesion that can
often be detected by routine screening methods ,no such preinvasive phase appears
to exist for NEC.
15. • These tumors often coexist with CIS, invasive SCC , or adenocarcinoma.
• It is important that we do not miss the NEC component, because the
prognosis of pure NEC is not significantly different from that of NEC admixed with non-
NEC.
16. SYMPTOMS:
• vaginal discharge,
abnormal vaginal
bleeding including
postcoital bleeding ,
pelvic pain.
• advanced disease can
include symptoms of
weight loss, abdominal
bloating, or symptoms
specific to metastatic
disease (liver, adrenals,
bone, bone marrow, and
the brain)
• Occasionally, like
neuroendocrine tumors
of the lung, small cell
cancer of the cervix can
present with
paraneoplastic
syndromes such as
hypercalcemia (elevated
blood calcium levels),
neurologic disorders,
Cushing’s syndrome,
and SIADH.
17. Workup:
• Pap smear- efficacy of it as a screening modality is unknown,
and it likely performs worse than it does for other cervical cancers.
Some women with NEC of the cervix have had normal annual Pap
smears leading up to the time they were diagnosed with cancer.
• Biopsy-These tumors can be mixed (have other components), but
a tumor with any NEC component no matter how small, should
be treated as so.
• Imaging
[Salvo G, et al. Int J Gynecol Cancer 2019;29:986–995. doi:10.1136/ijgc-2019-000504]
24. • Chromogranin A
• Synaptophysin
• Neuron specific enolase
• CD56
• Insulinoma-associated protein 1 (INSM1) may be more specific for
neuroendocrine tumors than chromogranin A or synaptophysin.
• Others
• HER-2/neu, epidermal growth factor receptor (EGFR), vascular endothelial growth
factor (VEGF), cyclooxygenase-2 (COX-2), estrogen receptor, and progesterone
receptor in small- and large-cell neuroendocrine cervical carcinomas
• In a recent systematic review, the most common mutations were in p53 (26%),
KRAS (12%), PIK3CA (18%), and c-myc (53%) genes.
, Loss of heterozygosity was found in 30% of cases.
[Tempfer CB, Tischoff I, Dogan A, et al. Neuroendocrine carcinoma of the cervix: a systematic review of the literature.
BMC Cancer2018;18:1–16.]
[Salvo G, et al. Int J Gynecol Cancer 2019;29:986–995. doi:10.1136/ijgc-2019-000504]
25. High-grade neuroendocrine cervical carcinoma
primary treatment algorithm
Salvo G, et al. Int J Gynecol Cancer 2019;29:986–995. doi:10.1136/ijgc-2019-000504
26. • Ishikawa et al of 93 patients
with stage I-II high-grade
neuroendocrine carcinoma of
the cervix
• Patients who underwent
radical surgery had a better
overall survival than those who
received definitive
radiotherapy (p=0.043).
27. • Wang et al reviewed 146 patients with
stage I-II disease.
• Of these, 116 (79%) underwent
surgery as part of their primary
treatment (primary surgery
with/without adjuvant therapy, NACT
plus RH, or peri-operative
chemotherapy plus radical
hysterectomy).
• The remaining 30 patients did not
undergo surgery but rather had
radiation therapy with or without
chemotherapy.
• The authors found there was a trend of
worse DFS and cancer-specific
survival for those women who had
radical surgery compared with those
who did not undergo surgery.
28. • Based on the conflicting results from multiple retrospective studies,
the role of surgery for early-stage NET seems unclear,
but surgery alone without adjuvant CT/RT is not appropriate for any
patient with high-grade NECC.
[Salvo G, et al. Int J Gynecol Cancer 2019;29:986–995.
doi:10.1136/ijgc-2019-000504]
30. Adj chemo ??
• Ishikawa et al found that there was
an improved DFS in 41 patients who
received adj CT with etoposide-
platinum or irinotecan-platinum
• Also, adjuvant chemotherapy after
surgery reduced extra-pelvic
recurrences with an OR of 0.37 p=0.047).
• A trend toward improved OS was also
observed when adj.chemotherapy was
given, but was not statistically
significant.
31. no of cycles of chemo ?
• Pei et al retrospectively
evaluated 92 patients with
stage I-II smallcell carcinomas
and found that adjuvant
chemotherapy with
cisplatin and etoposide for at
least five cycles was associated
with improved 5-year recurrence-
free survival compared with other
treatments ( p<0.001)
32. postop RT ??
• Japanese multicenter study,
the risk of pelvic recurrences
after surgery were lower if
patients received
postoperative radiation (16%)
versus patients who did not
undergo radiation (25%) but
the difference did not reach
significance
(p=0.6).
33. UTERUS PRESERVING SX,
Although FSS have been
reported in women with early-
stage small cell cervical cancer
uterine preservation fertility-
sparing treatment is not
recommended by (NCCN)
guidelines for cervical
neuroendocrine tumors.
34. • radical abdominal trachelectomy
with bilateral pelvic lymph node
dissection and upper para aortic
lymph node sampling was
performed. A prophylactic
cervical cerclage suture was also
inserted.
• 4cycles of cisplatin and
etoposide.
35. Fertility presevation.
• For ovarian preservation and
maintaining ovarian function
in patients with locally
advanced disease, one may
consider ovarian transposition.
• However, after external beam
pelvic radiation and/or
brachytherapy, ovarian
preservation is only maintained
in 65% of patients.
36. RECURRENT DISEASE
• For patients with recurrent disease, there
is limited consensus on the optimal
treatment approach with no standard
treatment protocols
37. Single agent
chemo in recurrent
settings
single-agent topotecan, irinotecan,
paclitaxel, or docetaxel as these regimens
are commonly used to treat recurrent small-
cell lung cancer.
single-agent regimens had very low activity
in patients with recurrent neuroendocrine
cervical cancer
38. • For patients with recurrent or
progressive disease who have
already been treated with a
platinum and etoposide
combination
• triplet regimen including
topotecan, paclitaxel, and
bevacizumab (TPB Regimen)
[As in Gynecologic Oncology Group (GOG)
240, a phase III study in patients with
recurrent cervical cancer (squamous cell
carcinoma, adenocarcinoma, and
adenosquamous carcinoma)]
39. Rationale for triplet regimen:
1. this regimen is tolerable in women who have previously undergone definitive
chemoradiation.
2.As single-agent paclitaxel or topotecan are active and frequently used in
recurrent small-cell lung cancer,
the combination would presumably be equally as active, and potentially more
active than the single-agent regimens.
3. small-cell cervical cancers express the VEGFr over 95% of the time
supporting the addition of bevacizumab as an active agent.
4. Finally, all three drugs have been approved by the US FDA for the treatment
of recurrent cervical cancer.
40. TPB regimen in rec NEC
• 13patients with TPB regimen were
compared with 21 patients
receiving other non TPB regimens
The triplet regimen was associated
with a significant improvement in
outcome
Results: PFS(mo) OS(mo)
TPB
Regimen
8 9.7
Non TPB
Regimen
4 9.4
42. MULTIPLE RECURRENCES:
• Immune checkpoint inhibitors and targeted therapies
may be beneficial when patients have suffered multiple
recurrences; however, the literature is limited in this
setting with only three case reports published to date.
43. • Paraghamian et al used
nivolumab in a patient with
recurrent, metastatic,
programmed cell death ligand-
1 (PD-L1)-negative small-cell
neuroendocrine cervical
carcinoma, who experienced a
complete response.
44. Sharabi et al.,
• metastatic, chemotherapy-
refractory neuroendocrine
carcinoma with bowel obstruction
due to a large tumor burden.
• Liquid biopsy demonstrated a high
number of tumor mutations.
• The patient was treated with
radiotherapy combined with
nivolumab and experienced a
near-complete systemic resolution
of disease for at least 10 months.
45. • Lyons et al used the mitogen-
activated protein kinase 1 (MEK)-
inhibitor trametinib in a woman
with recurrent small-cell
neuroendocrine cervical
carcinoma whose tumor was
found to have a KRAS mutation,
and had a complete radiologic
response three cycles.
46. • Nivolumab-
• brand name-opdivo
• iv
• monoclonal antibody
• MOA-binds to PD1 receptor & blocks its interaction with PD L1 &PDL2
releasing PD1 mediated inhibition of immune response
47. Phase II Study of Pembrolizumab in rec NEC of
female genital tract
phase II basket trial of pembrolizumab 200 mg
intravenously every 3 weeks in patients
Results-
7 women with gynecologic extrapulmonary
small cell carcinoma were enrolled, 6
with cervical and 1 with vulvar carcinoma.
No patient was progression free at 27 weeks
Conclusion:
Pembrolizumab alone showed minimal activity in
women with recurrent small
cell neuroendocrine tumors of the lower genital
tract.
48. Surveillance
• For cervical neuroendocrine tumors,
the SGO guidelines recommend physical exam and symptoms review
with periodic full-body imaging with either CT or PET/CT scan.
• The guideline does not give any recommendation on the frequency of such
follow-up and no data exist to make definitive recommendations.
[Gardner GJ, Reidy-Lagunes D, Gehrig PA. Neuroendocrine tumors of the gynecologic tract: a Society
of Gynecologic Oncology (SGO) clinical document. Gynecol Oncol 2017;122:190–8]
49. • 5yr survival for NEC of the cervix is worse
than that for other more common types of
cervical cancer (36 vs 60-70%)
• 5-year survival was 37% ( I-IIA disease)
versus 9% for those with more advanced
disease.
[Stoler, M.H., et al., Small-cell neuroendocrine carcinoma of the cervix. A human
papillomavirus type 18-associated cancer. Am J Surg Pathol, 1991]
50. Large cell NEC
• Large cell NECC are rare & aggressive type of ca cx
• Till now only 62 cases have been reportd in a study by Embry et al .
• median age is 37 years
• 58% had stage 1 ds
• Earlier stage and addition of chemotherapy associated with inproved survival
• RH with chemotherapy was the most commonly used mode of therapy in this study.
• Median overall survival (OS) was 16months;
[Albores-Saavedra J, Martinez-Benitez B, Luevano E. Small cell carcinomas and large cell neuroendocrine carcinomas
of the endometrium and cervix: polypoid tumors and those arising in polyps may have a favorable prognosis. Int J
Gynecol Pathol 2008; 27: 333-9.]
51.
52. CERVICAL CARCINOIDS
• they represent a specific type of cervical neoplasia derived from the
argyrophil cells, normally found in small numbers among the linings of the
endocervical glands and the cervical squamous epithelium.
• Lymphovascular space invasion (LVI) is not a prominent feature of
carcinoids, in contrast to high-grade neoplasms, in which 80% of cases
exhibit LVI
• IHC chromogranin and synaptophysin, significantly enhances the
diagnosis of neuroendocrine tumors, while testing for 24-h urinary 5-HIAA
may be useful in these cases
• Most reported cases with a cervical carcinoid diagnosis were diagnosed as
postoperative pathological findings
53. • Primary cervical carcinoids are extremely rare, and metastatic carcinoids should be
excluded to ensure a diagnosis of primary cervical carcinoid tumor.
• In 1976, Albores-Saavedra et al. reported 12 cases of ‘carcinoid’ tumor, dividing them
into well-differentiated and poorly differentiated types based on microscopic
findings.
• Cancers resembling islet cell tumors or medullary thyroid carcinoma were
diagnosed as well-differentiated ‘carcinoid,’ while those similar to oat cell carcinoma
of the lung were diagnosed as poorly differentiated ‘carcinoid.’
• Generally, the prognosis of TC and AC is better than that of LCNEC and SCNEC.
54. • Most carcinoid tumors demonstrate a remarkable tropism for the liver. Liver lesions should be
considered for resection to control tumor burden and those lesions that are not resectable should
be considered for regional embolization, radiofrequency ablation or cryotherapy
• somatostatin analogues can be used
• The use of conventional cytotoxic chemotherapy should be restricted primarily to patients with
poorly differentiated tumors.
• the effect of radiotherapy on these tumors has not been established
• the most effective treatment modalities for cervical carcinoids remain uncertain, because of the
small number of reported cases.
A Case of Cervical Carcinoid and Review of the Literature
Georgios Papatsimpas,a,* Ioannis Samaras,a Paraskevi Theodosiou,b Konstantina Papacharalampous,c Eleni Maragkouli,a N. Vasileios
Papadopoulos,a Konstantinos Tsapakidis,a Ioannis Litos,a Eleni Sogka,a Evanthia Kostopoulou,c and Georgios K. Koukoulisc
55. • a case of cervical
carcinoid treated
successfully with
radical hysterectomy
58. SCCOHT
• SCCOHC of the ovary is a highly aggressive neoplasm affecting young females
• associated with paraneoplastic hypercalcemia in two-thirds of cases.
• Microscopic findings show a sheet-like arrangement of cells punctured by
follicle-like spaces.
• The tumor cells are typically small and round with hyperchromatic nuclei and
brisk mitotic activity.
• Recently, somatic and germline SMARCA4 mutations &
loss of BRG1 protein expression IN IHC have been described in SCCOHTs.
[Neuroendocrine Tumors of the Female Reproductive Tract: A Literature Review
Yi Kyeong Chun]
59. • Avg age-24yrs
• All tumors are bilateral
• very poor prognosis
• only 33% survival in stage 1 ds & even
worse in advanced diseases.
60. SCCOHT pic
• fleshy appearance
• diffuse growth
pattern
• with focal areas of
follicle like spaces
• glassy eosinophilic
cytoplasm
62. • Treatment:
1. Sx(gross resection of ds)
followed by PT based
chemo(carbo+pac/EP)
2. Radiation therapy in selected
pts
3. high dose chemotherapy with
stem cell support
A Retrospective Study of the North Eastern
German Society of Gynecologic Oncology (NOGGO)*
JALID SEHOULI1§, HANNAH WOOPEN1§, MARIANNE PAVEL2,
ROLF RICHTER1, LISA-KATHRIN LAUTERBACH1, ELIANE TAUBE3,
SILVIA DARB-ESFAHANI3, CHRISTINA FOTOPOULOU4 and KLAUS
PIETZNER
• Treatment of
Hypercalcemia:
1.aggressive hydration
2.loop diuretics
3.bisphosphonates.
63. • According to a GCIG study:
multi-modality treatment approach
including surgery, chemotherapy with the
addition of radiotherapy either sequentially
or concurrently can be planned.
[surgical resection followed byAdjuvant
platinum-based chemotherapy was given
to all patients.
7 received adj.RT with either pelvic and
para-aortic radiotherapy, average dose
46.5 Gy (40 Gy/25# - 50.4 Gy/23#), or
pelvic and whole abdominal radiotherapy]
64. • Pautier et al
• optimal CRS and chemo protocol for
4-6cycles (PAVEP).
• In case of complete response, patients
received HDC with stem-cell support,
followed by pelvic radiotherapy.
• Conclusion: Intensive regimen
containing multidrug chemotherapy,
HDC and pelvic radiotherapy, for the
management of SCCOHT,
demonstrated encouraging survival
and should be proposed for all
patients. However, the significant
toxicity cost associated is of concern
and it should be restricted to expert
centers.
67. SCCOPT
• SCCOPT is a highly aggressive SCNEC and must be distinguished from
metastatic small cell carcinoma from other locations,particularly the
lung.
• These tumors are probably of surface epithelial origin because they are
frequently associated with surface epithelial tumors.
• In a study, 8/11 SCCOPT cases were associated with surface epithelial
tumors
[Eichhorn JH, Young RH, Scully RE. Primary ovarian small cell carcinoma of pulmonary type. A clinicopathologic,
immunohistologic, and flow cytometric analysis of 11 cases. Am J Surg Pathol 1992; 16: 926-38.]
• Perinuclear dot-like CK 20 staining has been reported in this tumor,
[Rund CR, Fischer EG. Perinuclear dot-like cytokeratin 20 staining in small cell neuroendocrine carcinoma of the ovary
(pulmonary-type). Appl Immunohistochem Mol Morphol 2006; 14: 244-8.]
70. treatment of SCCOPT
• No standardised
modality
• primary CRS
followed by chemo
• (pac/carb)/(PC)/PA
VEP/Carb+etoposi
de used
71. OVARIAN CARCINOIDS
• Ovarian carcinoid tumors are monodermal teratomas occurring in a pure
form (15%) or combined with other teratomatous components (85%), such
as a dermoid cyst or a struma ovarii.
• They can also be a component of mucinous and Brenner tumors
72. • Carcinoid tumors of the ovary can be primary or metastatic;
• these metastases are usually from gastrointestinal tumors.
• Metastatic tumor are usually
-bilateral
-have multinodular growth
-extraovarian tumor nodules
-LVSI
-have teratomatous elements
Reed NS, Gomez-Garcia E, Gallardo-Rincon D, et al. Gynecologic Cancer InterGroup (GCIG) consensus review for
carcinoid tumors of the ovary. Int J Gynecol Cancer 2014; 24: S35-41
73. Primary carcinoid tumors of the ovary are divided into
• insular,
• trabecular,
• strumal, and
• mucinous carcinoid
74. Insular carcinoid, considered to be of midgut derivation,
m/c type of primary ovarian carcinoid tumor.
It is composed of small acini and solid nests of round cells with uniform nuclei and
abundant eosinophilic cytoplasm.
Carcinoid syndrome occurs in about one-third of patients with insular carcinoid
Trabecular carcinoid, considered to be of hindgut or foregut derivation,
shows wavy ribbons or a trabecular arrangement of cells in a dense fibrous stroma.
Mucinous carcinoid, the least common type of ovarian carcinoid
-well differentiated mucinous carcinoid,
-atypical mucinous carcinoid,
-carcinoma arising in mucinous carcinoid, and
-mixed mucinous carcinoid
[Neuroendocrine Tumors of the Female Reproductive Tract: A Literature ReviewYi Kyeong Chun
Department of Pathology, Cheil General Hospital and Women's Healthcare CenteR]
78. IHC
• chromogranin,
• synaptophysin,
• CD56
• Others
- serotonin, gastrin, pancreatic polypeptide, glucagon, VIP,
prolactin, and somatostatin can be detected in about 25% of cases
• CDX2, TTF-1, PAX8, and CK 7 and 20 - for the discrimination of
primary and metastatic carcinoids.
[Sporrong B, Falkmer S, Robboy SJ, et al. Neurohormonal peptides in ovarian carcinoids: an immunohistochemical
study of 81 primary carcinoids and of intraovarian metastases from six mid-gut carcinoids. Cancer 1982; 49: 68-74.]
79. • Primary ovarian carcinoid tumors confined to the ovary and treated with
surgery alone are expected to have an excellent overall outcome.
• Mucinous carcinoids might have more aggressive behavior than other types
of ovarian carcinoids, particularly if associated with atypical features.
[Baker PM, Oliva E, Young RH, Talerman A, Scully RE. Ovarian mucinous
carcinoids including some with a carcinomatous component: a report of 17 cases. Am J Surg
Pathol 2001; 25: 557-68 ]
80. Large Cell NEC
• Primary ovarian LCNEC is extremely rare and has a worse prognosis than usual
ovarian carcinomas, even when the diagnosis is made at an early stage
• In most cases, there are concomitant ovarian surface epithelial tumors.
• The NEC component varies from 10% to 90% when it is combined with an epithelial
tumor or teratoma.
• Primary pure LCNEC of the ovary is very rare.
• LCNECs probably arise from the neuroendocrine cells present in surface epithelial-
stromal tumors or germ cell tumors.
[Choi YD, Lee JS, Choi C, Park CS, Nam JH. Ovarian neuroendocrine carcinoma, non-small cell type,
associated with serous carcinoma. Gynecol Oncol 2007;]
82. UTERINE NEC
• NETs of the endometrium include TC, SCNEC, and
LCNEC.
• Only 3 cases of primary endometrial Carcinoids have
been reported .
• 16 cases of small cell NEC of endometrium
• 25 cases of large cell NEC of endometrium.
• [Chetty R, Clark SP, Bhathal PS. Carcinoid tumour of the uterine corpus.
Virchows Arch A Pathol Anat Histopathol 1993; 422: 93-5]
83. • Only 16 cases of
small cell NEC of
endometrium have
been reported till
now.
85. • Prior studies reported mean survival of
approximately 22 months for stage I–II
disease and approximately 12 months for
stage III-IV tumors respectively
86. • Treatment strategies for NECE are not standardized.
• A variety of treatments including surgical resection,
radiotherapy,and platinum-based chemotherapy
• These treatment options are based in part on small cell lung cancer
data, but no large studies or prospective clinical trials have been
performed to guide treatment of NECE.
• Extrapolating from other tumor sites, chemotherapy for NECE often
consists of etoposide and a platinum analog.
[Huntsman DG, Clement PB, Gilks CB, Scully RE. Small-cell carcinoma of the endometrium: a clinicopathological study
of sixteen cases. Am J Surg Pathol 1994; 18: 364-75.]
87. neuroendocrine carcinoma of
endometrium.
• In this series of 25Large
cell NEC of endometrium
• all patients underwent
surgical resection[TAH
BSO,Omentectomy/LND] and 60%
received chemotherapy
while 28% underwent
radiotherapy.
[Neuroendocrine carcinoma of endometrium.June Y. Hou
a,c,d, Alexander Melamed a,c,d, Alfred I. Neugut a,b,c,d,
Dawn L. Hershman a,b,c,d, Jason D. Wright
a,c,d,⁎Kathryn Schlechtweg a, Ling Chen a, Caryn M. St.
Clair a,c,d, Ana I. Tergas a,b,c,d, Fady Khoury-Collado
a,c,d,]
88. • Unlike neuroendocrine tumors of other
sites of female genitalia, LCNEC is more
common than SCNeC in endometrium.
90. NEUROENDOCRINE TUMORS
OF VAGINA
• Primary small cell neuroendocrine carcinoma of the vagina, first reported in 1984 by
Scully et al., is a rare neoplasm
• only 26 reported cases in English literature to date
• Occurrence of this tumor is common in postmenopausal females
• These lesions have propensity for early, widespread dissemination
• Regardless of the extent of disease at present, most patients die due to distant
metastasis
• Synaptophysin and chromogranin are the principle markers for neuroendocrine
tumors.
93. Multimodality treatment
• Excision ,adjuvant chemotherapy
followed by intracavitary vaginal
brachytherapy.
• This regimen consisted of vincristine 1.4
mg/m2, doxorubicin 50 mg/m2, and
cyclophosphamide 1000 mg/m2 at 21-day
intervals for 6 courses,
followed by 70 Gy administered by
vaginal cylinder.
96. VULVAL NEUROENDOCRINE
TUMORS
• Neuroendocrine tumor (Merkel
cell carcinoma-MCC) of the
vulva is a very rare entity with
less than 15 cases reported in
the literature.
• It is known for its aggressive
behaviour and propensity for
early dissemination.
• The actual cell of origin and
etiology of this disease is
controversial.
• In absence of any definite
guidelines for management
(due to its rarity), extrapolation
of data from extra-vulvar MCC
seems logical.
97. Carcinoid tumors of vulva
• 3cases in 3 middle-aged women who
presented with a solitary vulvar nodule
without any other associated symptoms.
• treated with simple local excision.
• tumors were composed exclusively of clear
cells
• IHC for chromogranin and neuron-
specific enolase confirmed neuroendocrine
differentiation in all cases.
• Follow-up of 5.5 to 16 years showed no
evidence of recurrence or metastasis.
• Primary clear cell carcinoid tumors of the
vulva need to be considered in the
differential diagnosis of vulvar masses
with clear cell features
98. CONCLUSION
• NENs and carcinomas, as zebras of the oncology world that are fraught
with heterogeneity, intrinsically complex which is anathema to
standardization and uniformity of treatment and outcome.
• Fortunately, a renaissance of chemotherapeutic agents, small molecules,
and biological therapies that have progressed to clinical trials provides a
hope in the treatment of these complicated and confounding tumors.
