Definition/General
Introduction:
Endometrial carcinoid is an extremely rare neuroendocrine tumor of the uterus
It represents less than 0.1% of all uterine malignancies
It shows neuroendocrine differentiation with characteristic morphology
It can be pure carcinoid or mixed with other components.
Origin:
May arise from neuroendocrine cells in endometrium
Possible origin from argyrophil cells
Can develop from multipotent stem cells
May occur as part of mixed neuroendocrine-epithelial neoplasm
Rare primary uterine location.
Classification:
Classified as neuroendocrine tumor by WHO classification
Well-differentiated neuroendocrine tumor
Grade 1 or 2 based on mitotic rate and Ki-67
May be pure or mixed with adenocarcinoma
Low to intermediate grade malignancy.
Epidemiology:
Extremely rare tumor
Peak incidence in 6th-7th decades
Postmenopausal women predominantly affected
No clear ethnic predilection
Often diagnosed at early stage
Better prognosis than poorly differentiated neuroendocrine carcinomas.
Clinical Features
Presentation:
Abnormal uterine bleeding (most common)
Postmenopausal bleeding
Carcinoid syndrome rare
Pelvic mass
Incidental finding in some cases.
Symptoms:
Heavy uterine bleeding
Pelvic pain
Hormonal symptoms possible
Carcinoid syndrome (flushing, diarrhea) extremely rare
Constitutional symptoms uncommon.
Risk Factors:
Age >60 years
Multiple endocrine neoplasia syndromes (rare)
Neurofibromatosis (rare association)
Previous hormone therapy
Family history of neuroendocrine tumors.
Screening:
No specific screening recommendations
24-hour urine 5-HIAA if carcinoid syndrome suspected
Chromogranin A serum levels
Imaging studies for staging
Octreotide scan may be positive.
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Gross Description
Appearance:
Well-circumscribed polypoid mass
Tan-yellow cut surface
Firm consistency
Homogeneous appearance
Minimal necrosis typically.
Characteristics:
Size ranges from 1-6 cm
Smooth external surface
Cut surface shows solid, uniform appearance
Yellow-tan color
Well-demarcated from surrounding tissue.
Size Location:
Usually small at presentation
Mean size 3-4 cm
Involves endometrial cavity
Polypoid configuration common
Superficial location typical.
Multifocality:
Usually unifocal presentation
Limited local invasion
Lymphovascular invasion uncommon
Lymph node metastases rare
Distant metastases unusual.
Microscopic Description
Histological Features:
Uniform cells in organoid patterns
Nested or trabecular arrangement
Salt-and-pepper chromatin pattern
Inconspicuous nucleoli
Low to moderate mitotic activity
Minimal pleomorphism.
Cellular Characteristics:
Small, uniform cells
Round to oval nuclei
Finely granular chromatin
Moderate eosinophilic cytoplasm
Indistinct cell borders
Nuclei with salt-and-pepper appearance.
Architectural Patterns:
Insular pattern (most common)
Trabecular pattern
Acinar pattern
Solid nests
Ribbon-like arrangements
Rosette formation may be present.
Grading Criteria:
Grade 1: <2 mitoses/10 HPF, Ki-67 <3%
Grade 2: 2-20 mitoses/10 HPF, Ki-67 3-20%
Grade 3: >20 mitoses/10 HPF, Ki-67 >20% (poorly differentiated).
Immunohistochemistry
Positive Markers:
Chromogranin A (positive)
Synaptophysin (positive)
CD56 (NCAM, positive)
Neuron-specific enolase (NSE)
Vimentin
TTF-1 (may be positive)
CDX2 (variable).
Negative Markers:
Cytokeratins (usually negative)
EMA (negative)
S-100 (negative)
Desmin (negative)
Smooth muscle actin (negative)
LCA (negative).
Diagnostic Utility:
Chromogranin A and Synaptophysin confirm neuroendocrine differentiation
CD56 supports diagnosis
Ki-67 for grading
Negative epithelial markers distinguish from carcinoma
Pancytokeratin may be focally positive.
Molecular Subtypes:
No established molecular subtypes
Chromosomal gains and losses
TP53 mutations uncommon
Rb loss in high-grade tumors
Chromatin remodeling gene mutations.
Molecular/Genetic
Genetic Mutations:
MEN1 mutations (if part of MEN syndrome)
Chromosomal instability
11q deletions
18q deletions
ATRX mutations (pancreatic NETs)
DAXX mutations (pancreatic NETs).
Molecular Markers:
Loss of 11q (MEN1 locus)
Chromosomal alterations
ATRX/DAXX loss (alternative lengthening of telomeres)
mTOR pathway activation
VEGF expression.
Prognostic Significance:
Grade most important prognostic factor
Size <2 cm indicates better prognosis
Mitotic rate correlates with outcome
Ki-67 index predicts behavior
Stage at presentation important.
Therapeutic Targets:
Somatostatin analogues (octreotide, lanreotide)
mTOR inhibitors (everolimus)
VEGF inhibitors (sunitinib)
PRRT (peptide receptor radionuclide therapy)
Surgical resection primary treatment.
Differential Diagnosis
Similar Entities:
Poorly differentiated neuroendocrine carcinoma
Metastatic carcinoid (GI tract, lung)
Endometrial stromal tumor
Paraganglioma
Primitive neuroectodermal tumor.
Distinguishing Features:
Poorly differentiated NEC: High mitotic rate, high Ki-67
Metastatic: Primary site evident
Stromal tumor: CD10 positive
Carcinoid: Chromogranin/Synaptophysin positive
Paraganglioma: S-100 positive sustentacular cells.
Diagnostic Challenges:
Distinguishing from metastatic carcinoid
Recognizing neuroendocrine morphology
Grading based on mitotic count and Ki-67
Excluding other neuroendocrine tumors
Immunohistochemistry essential.
Rare Variants:
Insular carcinoid
Trabecular carcinoid
Mixed adenocarcinoma-carcinoid
Goblet cell carcinoid (rare in uterus)
Atypical carcinoid.
Sample Pathology Report
Template Format
Sample Pathology Report
Complete Report: This is an example of how the final pathology report should be structured for this condition.
Specimen Information
[specimen type], measuring [size] cm, firm consistency
Diagnosis
Neuroendocrine tumor (carcinoid) of the endometrium
WHO Classification
Well-differentiated neuroendocrine tumor, Grade [1/2/3]
Histological Features
[Insular/trabecular/mixed] pattern, mitoses: [count]/10 HPF
Grade
WHO Grade: [1/2/3] based on mitotic count and Ki-67
Immunohistochemistry
Neuroendocrine markers: Chromogranin A [+/-], Synaptophysin [+/-], CD56 [+/-]
Ki-67: [percentage]%
TTF-1: [+/-], CDX2: [+/-]
Invasion
Myometrial invasion: [present/absent], depth: [specify if present]
Final Diagnosis
Well-differentiated neuroendocrine tumor (carcinoid), Grade [1/2/3]