Definition/General

Introduction:
-Ovarian carcinoid tumor is a rare neuroendocrine tumor of the ovary
-Accounts for <1% of ovarian tumors
-May arise from teratomatous elements or de novo
-Can cause carcinoid syndrome in 30% cases.
Origin:
-Originates from neuroendocrine cells within teratomatous tissue or directly from ovarian stroma
-Shows neuroendocrine differentiation
-Produces serotonin and other hormones
-Similar to carcinoids elsewhere.
Classification:
-Primary ovarian carcinoid (most common)
-Carcinoid arising in teratoma
-Metastatic carcinoid (from GI tract)
-Insular type (most common)
-Trabecular type
-Strumal carcinoid
-Mucinous carcinoid.
Epidemiology:
-Peak incidence in 5th-6th decades
-Mean age 50-55 years
-Unilateral in >95% cases
-Carcinoid syndrome in 30%
-Better prognosis than GI carcinoids.

Clinical Features

Presentation:
-Pelvic mass (most common)
-Carcinoid syndrome (flushing, diarrhea, wheezing) in 30%
-Abdominal pain
-Abdominal distension
-Right heart failure (advanced cases).
Symptoms:
-Abdominal/pelvic mass (80-90%)
-Flushing episodes (30%)
-Diarrhea (25%)
-Wheezing/bronchospasm (20%)
-Abdominal pain (60%)
-Weight loss (advanced)
-Heart palpitations.
Risk Factors:
-Postmenopausal age
-Previous teratomas
-Family history unclear
-No established environmental factors
-Genetic predisposition rare
-Associated with other neuroendocrine tumors (rare).
Screening:
-Serum serotonin (elevated)
-5-HIAA (24-hour urine)
-Chromogranin A (elevated)
-Neuron-specific enolase
-Pelvic ultrasound
-CT/MRI for staging
-Octreotide scan.

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Gross Description

Appearance:
-Solid, well-circumscribed mass
-Yellow-tan to gray cut surface
-Size ranges from 2-15 cm
-Smooth capsule
-Homogeneous appearance
-May have cystic areas.
Characteristics:
-Unilateral in >95% cases
-Encapsulated appearance
-Cut surface shows solid homogeneous areas
-Yellow-tan color
-Firm consistency
-Hemorrhage and necrosis rare.
Size Location:
-Variable size (1-20 cm)
-Average size 6-10 cm
-No specific ovarian location preference
-Usually smaller than epithelial tumors
-Slow growth pattern.
Multifocality:
-Usually unifocal
-Bilateral involvement rare (<5%)
-May arise within teratomatous areas
-Metastases to liver, lymph nodes in advanced cases.

Microscopic Description

Histological Features:
-Uniform small cells with round nuclei
-Insular pattern (most common)
-Trabecular pattern
-Ribbon-like arrangements
-Eosinophilic cytoplasm
-Salt-and-pepper chromatin.
Cellular Characteristics:
-Small, uniform cells
-Round to oval nuclei
-Finely granular chromatin (salt-and-pepper)
-Inconspicuous nucleoli
-Moderate eosinophilic cytoplasm
-Low mitotic rate.
Architectural Patterns:
-Insular pattern (solid nests)
-Trabecular pattern (cords and ribbons)
-Acinar pattern (rare)
-Solid pattern
-Mixed patterns common.
Grading Criteria:
-Well-differentiated (Grade 1): Mitoses <2/10 HPF
-Moderately differentiated (Grade 2): 2-20 mitoses/10 HPF
-Poorly differentiated (Grade 3): >20 mitoses/10 HPF
-Necrosis indicates higher grade.

Immunohistochemistry

Positive Markers:
-Chromogranin A (90-95%)
-Synaptophysin (85-90%)
-CD56 (80-85%)
-Neuron-specific enolase (70-80%)
-Serotonin (70-80%)
-Cytokeratin (dot-like)
-TTF-1 (variable).
Negative Markers:
-AFP (negative)
-Beta-hCG (negative)
-Inhibin (negative)
-Calretinin (negative)
-WT1 (negative)
-Vimentin (usually negative).
Diagnostic Utility:
-Neuroendocrine markers confirm diagnosis
-Chromogranin and synaptophysin essential
-Serotonin positivity supports carcinoid
-Distinguish from other small cell tumors
-Hormone-specific staining.
Molecular Subtypes:
-Similar to GI carcinoids
-MEN1 mutations (rare)
-Chromosomal losses (11q, 18q)
-SSTR expression (somatostatin receptors)
-Low mutation burden.

Molecular/Genetic

Genetic Mutations:
-MEN1 mutations (rare)
-Chromosomal losses (11q13, 18q21)
-ATRX mutations (rare)
-DAXX mutations (rare)
-mTOR pathway alterations.
Molecular Markers:
-Somatostatin receptor expression
-Chromogranin A overexpression
-Synaptophysin expression
-Low Ki-67 proliferation index
-p53 wild-type usually.
Prognostic Significance:
-Stage most important factor
-Size >10 cm worse prognosis
-Mitotic rate and grade important
-Carcinoid syndrome indicates advanced disease
-Better prognosis than GI carcinoids.
Therapeutic Targets:
-Surgical resection primary treatment
-Somatostatin analogs (octreotide, lanreotide)
-Targeted therapy (everolimus, sunitinib)
-Peptide receptor radionuclide therapy
-Chemotherapy (advanced cases).

Differential Diagnosis

Similar Entities:
-Metastatic carcinoid (from GI tract)
-Small cell carcinoma
-Granulosa cell tumor
-Stromal tumors
-Neuroendocrine carcinoma.
Distinguishing Features:
-Primary carcinoid: Unilateral
-Better differentiated
-Metastatic: Often bilateral
-GI primary
-Small cell: High-grade features
-TTF-1 positive
-Granulosa: Inhibin positive
-Coffee-bean nuclei.
Diagnostic Challenges:
-Primary vs metastatic distinction
-GI tract evaluation essential
-Grade assessment
-Hormone production correlation
-Staging accuracy.
Rare Variants:
-Strumal carcinoid (with thyroid tissue)
-Mucinous carcinoid
-Goblet cell carcinoid
-Large cell neuroendocrine carcinoma
-Mixed neuroendocrine-epithelial.

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

Ovarian mass, [side], measuring [X x Y x Z] cm

Diagnosis

Carcinoid Tumor, Grade [1/2/3]

Classification

WHO Classification: Neuroendocrine Tumor, Carcinoid

Histological Features

Shows [insular/trabecular/mixed] pattern with uniform neuroendocrine cells

Grading

Grade [1/2/3]: [X] mitoses/10 HPF, [presence/absence] of necrosis

Special Studies

IHC: Chromogranin A [positive], Synaptophysin [positive], Ki-67 [X]%

Serotonin: [X] ng/mL, 5-HIAA: [X] mg/24h

Final Diagnosis

Ovarian Carcinoid Tumor, Grade [1/2/3], [Side]