Frozen Section Diagnosis, Indications and Pitfalls
Section 1 -
Bone and Gynecologic Specimens
Anthony Montag, M.D.
Aliya N. Husain, M.D.
Jerome B. Taxy, M.D.
Frozen Sections: a Brief History 
|1891 ||William Welch produces frozen section for Halstead at Johns Hopkins. Unfortunately the operation was completed long before the slide was ready |
|1895 ||Cullen, working in Welch's lab, reports a 15 minute frozen technique|
|1896 ||Plenge (Heidelberg) and Pick (Berlin) report frozen section techniques. Pick credit Cullen, Plenge claims credit|
|1897 ||Kanthack and Pigg (Cambridge) publish their method for frozen section, which includes boiling the tissue in water for 5 minutes prior to freezing|
|1905 ||Wilson (Mayo clinic) develops frozen technique using methylene blue and publishes in JAMA. Generally credited with developing the frozen section.|
|1905-1925 ||Frozen section primarily done in private hospitals|
|1921 ||American Society of Clinical Pathology formed as professional society to elevate the status of Pathologist that provided services for live patients (rather than autopsy and research).|
|1927 ||Bloodgood (surgeon, Hopkins) states that surgery should not be performed in hospitals that do not have frozen section readily available.|
Indications for Frozen Section:
make an intraoperative decision concerning further surgery (excision, staging)
assess adequacy of specimen when an open biopsy is being preformed
plan work-up and special studies on the specimen
Quality Assurance Indicators in Frozen Section:
Frozen section turn around time. 
90% of frozen section slides should be ready to read within 15 minutes of receipt
90% of frozen section diagnoses should be reported within 20 minutes of receipt
Frozen section discrepancy
The discrepancy rate between frozen and permanent diagnoses is approximately 2% 
Most are sampling issues
The acceptable rate for diagnostic error is 1%
The more experienced the laboratory, the lower the deferral rate.
Mayo defers 2% 
A private hospital based study deferred 4.6% 
Case 1. Chondroblastoma
The differential diagnosis of an epiphyseal lesion is chondroblastoma, giant cell tumor, and clear
cell chondrosarcoma. Before viewing the frozen section slide, this differential can be ranked by
additional features such as age and radiologic features. Chondroblastoma is more centrally located than
giant cell tumor, which is typically eccentric and frequently expands the contour of the bone. Clear
cell chondrosarcoma radiographically resembles chondroblastoma, with central location, although it may
extend from epiphysis to the articular cartilage, and may be heavily mineralized. Both clear cell
chondrosarcoma and giant cell tumor occur in an older age group than chondroblastoma, albeit overlapping.
Histologically chondroblastoma presents a sheet of polygonal cells with disturbingly irregular and
dark nuclei on close inspection. Touch preps highlight the oval nucleus, occasionally with a
longitudinal cleft. True pleomorphism is absent, and mitotic figures are rare. Scattered
osteoclast-like giant cells may mimic giant cell tumor, however the stromal cell of giant cell tumor is
less polygonal and has finer chromatin. Giant cells are usually more diffusely distributed in giant cell
tumors. Chondroblastomas have a stromal background varying from a fine chicken wire pattern of calcified
cartilage matrix, to hyaline cartilage, frequently calcified, to pink zones of "osteoid-like" cartilage
matrix. Although reactive bone formation may be seen at the edge of the lesion or associated with
fracture, scattered well-formed spicules of lamellar bone, as frequently seen in clear cell
chondrosarcoma, are never seen in chondroblastoma.
Features of epiphyseal lesions
| ||Chondroblastoma ||Giant Cell Tumor ||Clear Cell Chondrosarcoma|
|Radiology ||Epiphyseal, central, usually not expanding the contour of the bone ||Epiphyseal, often with metaphyseal involvement, expansile, lytic ||Epiphyseal, central, not expansile, but may extend from epiphysis to articular cartilage|
|Age ||10 to 20 ||20 to 40 ||20 to 40|
|Cells ||Polygonal ||Oval to plump spindled stromal cells ||Abundant clear cytoplasm|
|Nucleus ||Smudgy, notched, atypical looking, but uniform ||Oval and similar to giant cell nuclei ||Uniform, large, clear blown out chromatin, large nucleoli|
|Matrix ||Cartilage, chicken wire calcified matrix, pink osteoid-like matrix ||Reactive bone at edges or secondary to fracture. No matrix ||Loose cartilage matrix with calcification. Well formed spicules of lamellar bone|
|Giant cells ||Scattered to numerous ||Usually diffuse and numerous ||Scattered|
Case 2 Aneurysmal Bone Cyst
Case 3 Telangiectatic Osteosarcoma
The intraoperative differentiation of cellular cystic lesions of bone is difficult, and is accompanied
by the risk of misdirecting the surgeon to do a primary curetting of a malignant lesion, contaminating
the surgical site with tumor and losing the opportunity to perform limb-sparing surgery.
Both aneurysmal bone cyst and telangiectatic osteosarcoma may present as an expansile, purely lytic,
cystic mass, frequently with fluid-fluid levels on CT or MRI examination, indicating layers of fresh and
old blood in a cystic space. Grossly, the biopsy material may appear similar: hemorrhagic, fleshy, with
cystic spaces and little bone matrix. Microscopically, both ABC and telangiectatic osteosarcoma have
cyst-like spaces without an endothelial lining. The septae are generally more cellular in telangiectatic
osteosarcoma, and are frequently broader. Osteoclast-like giant cells are present in both. Frank
pleomorphism and frequent and atypical mitotic figures are seen in most cases of telangiectatic
osteosarcoma, while the stromal cells of ABC are uniform and display occasional mitoses. Osteoid
production is difficult to find in most cases of telangiectatic osteosarcoma, but when present is
typically a fine meshwork of woven bone. Osteoid may be present in ABC, but tends appear as broader
seams of woven bone with histologically benign osteocytes and osteoblasts. In the absence of fracture,
the presence of necrosis in a cystic lesion of bone is an ominous sign is highly suggestive of
Features differentiating aneurysmal bone cyst from telangiectatic
| ||Aneurysmal Bone Cyst ||Telangiectatic osteosarcoma|
|Radiology ||Expansile, lytic, cystic fluid-fluid levels ||Expansile, lytic, cystic fluid-fluid levels|
|Peak Age ||10 to 20 ||10 to 20|
|Low power ||Cystic spaces, webs, blood ||Cystic spaces, webs, blood|
|Cells ||Short spindled stromal cells, fibroblasts ||Spindled to polygonal stromal cells, pleomorphic giant cells|
|Nucleus ||Sometimes reactive but uniform ||Pleomorphic, size variability,|
|Mitoses ||Occasional, but normal ||Atypical|
|Giant cells ||Osteoclast-like, frequently at edges of cyst wall ||Osteoclast-like and pleomorphic|
|Matrix ||Reactive woven and lamellar bone may be present ||Rare fine network of osteoid|
|Necrosis ||Hemorrhage, but not tumor necrosis ||Tumor necrosis is highly suggestive of Telangiectatic osteosarcoma|
Case 4 Chronic (Granulomatous) Osteomyelitis, North American Blastomycosis
Case 5 Langerhans Cell Histiocytosis (Histiocytosis X, Eosinophilic Granuloma)
A radiograph showing a lytic intramedullary lesion with ill-defined borders and periosteal reaction
raises the differential of a "marrow cell process", which includes chronic osteomyelitis, Langerhans cell
histiocytosis, Ewing's sarcoma and metastasis. Although chronic osteomyelitis may occur at any age,
hematogenously seeded osteomyelitis is most common in children and immunocompromised adults.
Histiocytosis X and Ewing's are both most common before the age of 30. Metastases are more common in
Histologically Ewing's separates from the differential diagnosis on low power because of the mixed
cell population, histiocytes, and inflammatory cells, while chronic osteomyelitis and Histiocytosis X may
appear similar. The folded nucleus of the Langerhans cell and the bilobed nucleus of the eosinophils
characterize Histiocytosis X. It is useful to note both the cytoplasmic staining and nuclear features of
the segmented cells, as poorly stained frozen sections frequently do not show eosinophilic granules.
Fragmented devitalized bone, displaying empty lacunae and a bluish dustiness to the edge, usually
accompanied by neutrophils, is highly suggestive of osteomyelitis. In the absence of fracture
eosinophilic granuloma does not usually display necrosis.
Features differentiating Langerhans histiocytosis from chronic
| ||Langerhans cell histiocytosis ||Chronic osteomyelitis|
|Radiology ||Intramedullary ill defined lytic diaphyseal lesion. Frequently craniofacial bones ||Intramedullary ill defined lytic diaphyseal lesion|
Rarely effects craniofacial bones
|Peak Age ||<30 ||Hematogenously spread is more common in children|
|Low power ||Mixed infiltrate of inflammatory and mononuclear cells ||Mixed infiltrate of inflammatory and mononuclear cells. Devitalized bone|
|Cells ||Langerhans cells. Eosinophils, but sometimes neutrophils or plasma cells predominate. ||Neutrophils, lymphocytes and plasma cells. Sometimes prominent histiocytic infiltrate or granulomas|
|Nucleus ||Grooved Langerhans nuclei, bilobed eosinophils ||Reniform macrophages|
|Mitoses ||Not prominent ||Not prominent|
|Giant cells ||May have giant cells composed of Langerhans cells, with similar nuclei ||Osteoclasts, or foreign body giant cells if chronic (fungal) or Langhans if TB|
|Matrix ||No matrix unless fracture or reactive border ||Devitalized bone and remodeling may be present|
|Necrosis ||With fracture ||Frequent|
Case 6: Metastatic Renal Cell Carcinoma
In adults, metastatic lesions by far outnumber primary bone tumors and as a rule, any lytic lesion in
a patient over 40 years old is a metastasis till proven otherwise. That being said, it is vital during
the intraoperative consultation to differentiate a metastasis from a known or occult primary from a
primary bone tumor. The usual therapeutic approach to a metastatic lesion that threatens to fracture is
to rod, plate, or otherwise stabilize the bone, without attempt to keep the surgical field free of
tumor. Primary lesions are candidates for limb salvage, and rendering an incorrect intraoperative
diagnosis of a metastatic lesion may lead to subsequent amputation. One study found a local recurrence
rate of 83% for erroneously curetted osteosarcoma cases that were subsequently treated by limb salvage,
as opposed to 8% for cases that were not curetted. 
Radiographically, a lytic or mixed lytic and blastic lesion may be either a primary or a metastatic
lesion. With the exception of primary vascular lesions and fibrous dysplasia, most primary bone lesions
are unifocal. However unifocal metastases are common, with nearly half of all osseous renal cell
metastases presenting as solitary lesions. 
Since metastases frequently present as fractures, secondary repair changes often complicate the
histologic picture. The first specimen submitted for frozen is frequently periosteum with fracture
callus or procallus, and may tempt a diagnosis of benign or malignant primary bone lesion. The majority
of carcinomas are easily differentiated from a primary bone tumor, however 10% of renal cell carcinoma
have areas of sarcomatoid differentiation, mimicking a high grade primary sarcoma of bone. Primary bone
lesions may also mimic epithelial tumors, particularly in the case of epithelioid hemangioendothelioma or
Features of primary vs metastatic bone lesions
| ||Primary ||Metastasis|
|Age ||All ages ||Most common over 40|
|Radiograph ||Lytic or blastic ||Lytic (lung, kidney) or blastic (prostate, breast)|
Purely lytic lesions may be silent on bone scan
Cortical based lesion more commonly renal cell
|Multifocality ||Rare, usually in same limb|
|History of primary elsewhere ||Doesn't rule out a second primary in bone ||Approximately 30% have skeletal met as first sign |
|Site ||Appendicular skeleton most common, but anywhere ||Trunk, proximal appendicular, marrow bearing areas|
|Presentation ||Pain, fracture ||Pain, fracture|
Case 7: Osteoblastic Osteosarcoma
Case 8: Fracture Callus Complicating Intraosseous Cyst
Many benign and malignant lesions present acutely as fractures. The differentiation of malignant bone
formation from reactive bone on frozen section is particularly difficult since fracture callus can
present with many of the elements of osteosarcoma: sheets of large osteoblasts, mitotic activity, woven
bone, immature cartilage matrix, and cellular fibroblastic proliferation.
Recent fractures of less than a week are unlikely to display osteoid matrix, however small subclinical
fractures may have occurred before presentation.
Maturation stages of fracture
|Days after fracture ||Feature|
|< 3 days ||Hemorrhage, edema, tissue necrosis|
|3 to 7 days ||Reactive myofibroblasts, tissue culture|
|7 to 10 days ||Increasing cellularity, early wisps of osteoid|
|>10 days ||Osteoid and cartilage matrix|
|2 to 3 weeks ||Osteoblast rimming, broad seams of osteoid|
Features of osteosarcoma and fracture on Frozen Section
| ||Osteosarcoma ||Fracture|
|Radiology ||Evidence of osteoid formation, Codman's triangle ||Early; underlying lesion is prominent|
Late; callus has symmetrical expansion of contour
|Low power ||Sheet-like and disorganized|
Borders infiltrate and entrap pre-existing spicules of lamellar bone
|Zonal distribution of elements|
Gradual transitions between fibroblastic, osteoblastic and cartilaginous areas
Borders tend to be sharper, with no infiltration and trapping of lamellar bone, but with remodeling of devitalized bone in fracture zone
|Osteoid ||Confluent, fine net or mesh-like osteoid, not organizing architecturally ||Tendency to form broader spicules of woven bone with linearity|
When mature, palisades of Roman arches
|Rimming ||Osteoblast rimming usually not seen in conventional osteosarcoma ||Osteoblast rimming prominent|
|Atypia ||Osteoblasts have nuclear size and chromatin heterogeneity|
When woven bone trabeculae are present, the entrapped osteoblasts are atypical
|Osteoblasts are reactive with abundant cytoplasm, often with prominent Golgi apparatus, but not heterogenous or overtly atypical. Osteocytes within broader trabeculae of osteoid become blander|
|Mitoses ||Frequent and atypical ||Frequent|
|Stroma ||Stroma between trabeculae is cellular and has fine osteoid ||Stroma between trabeculae is vascular and represents a granulation tissue response|
|Extraosseous extension ||Periosteal elevation, usually not trapping muscle or fat ||Elements injured by the fracture, such as muscle and fat, may be engulfed by the callus|
Case 9: Low Grade Central Osteosarcoma, Fibrous Dysplasia-like
Low-grade central osteosarcoma may present with several histologies resembling benign bone lesions,
including chondromyxoid fibroma and fibrous dysplasia.
Low-grade central osteosarcoma is usually favored clinically over fibrous dysplasia by the
aggressiveness of the radiographic appearance. Cortical erosion, involvement of the epiphysis, irregular
borders and coarse trabeculation all favor low-grade central osteosarcoma. A clinical history of pain is
also suggestive, as most cases of fibrous dysplasia present with deformity without chronic pain.
Histologically the lesions can appear very similar, but the recognition of long spicules of mixed
lamellar and woven bone favors OS, even in the absence of overt anaplasia. If suspected, it is best to
request additional diagnostic material for permanents and defer.
Features of low cellularity osteoid producing lesions
| ||Low grade central osteosarcoma ||Fibrous dysplasia|
|Age ||20 to 40 peak age ||Usually < 30|
|Location ||Long bone lower extremity metaphysis ||Any bone, metaphyseal|
|Symptom ||Pain ||Swelling deformity|
|Radiograph ||Lytic medullary lesion, ground glass, may destroy cortex but usually no periosteal reaction. If coarsely trabeculated, think low grade central OS ||Lytic medullary lesion, lucent or ground glass, but more uniform, usually better circumscribed. Does not involve epiphyseal plate|
May be multifocal
|Stroma ||Low cellularity, may be fibromatosis-like. May coalesce around spicules ||Low cellularity|
|Osteoid ||Mixed woven and lamellar bone. Characteristic long parallel streamers, as in parosteal OS ||Woven bone only, short trabeculae are more curled|
|Osteoblast rimming ||Usually can find easily ||Only focal|
|Atypia ||May be subtle to impossible to see on FS ||Absent|
|Mitoses ||Rare ||Rare|
Case 10: Enchondroma
Differentiating enchondroma from low-grade chondrosarcoma is a difficult differential on frozen
section, and should be approached with full knowledge of clinical history, symptoms, radiology, site, and
surgical intraoperative impression. Several caveats should be heeded:
- Asymptomatic lesions are usually benign
- Lesions of the hand and feet, although they may be cellular and atypical enough to warrant a diagnosis
of Grade II chondrosarcoma in other sites, are benign until proven otherwise
- Small lesions and lesions in patients less than 30 y/o are almost always benign
- Myxoid stroma is more likely malignant
- Necrotic cartilage in the absence of a fracture is probably malignant
- Infiltrative growth pattern is diagnostic of malignancy
Features of enchondroma and low grade chondrosarcoma
| ||Enchondroma ||Low Grade Chondrosarcoma|
|Age ||Teens to elderly ||Most over 50|
|Symptoms ||Usually asymptomatic, incidentally discovered. If painful, usually associated with fracture ||Progressive pain, night pain, mass|
|Distribution ||Hands and feet, femur, humerus, tibia ||Pelvis, femur, humerus, ribs, scapula|
|Location ||Diaphysis, metaphysis, uncommon epiphyseal ||Same|
|Size ||Usually 6 cm or less ||Larger|
|Low power ||Islands of cartilage with ossification to lamellar bone at rim, no trapped lamellar bone ||Infiltrative pattern, trapped native lamellar bone, infiltration of Haversion canal, Lobules separated by fibrous bands|
|Cellularity ||Low cellularity, Fewer than 25 cells per 400X hpf, likely benign ||Variable, but if greater than 100 cells per hpf (400x) then likely malignant|
|Mitoses ||< 1/50 hpf ||More than 2/50 hpf|
|Radiology ||Sharply defined radiolucency with cloud-like calcification. Without erosion of cortex and without periosteal extension ||Less well defined, may expand contour of bone, scallop the cortex, and show periosteal reaction|
|Matrix ||Hyaline, not myxoid ||May be myxoid|
|Cytology ||Small nuclei ||Atypia, prominent nucleoli|
Case 11: Granulosa Cell Tumor
Case 12: Undifferentiated Ovarian Carcinoma
Granulosa cell tumors are typically unilateral and although they may occur in all ages, are more
common in adults. The tumors may be large, and occasionally present as an acute abdomen due to ovarian
torsion, rupture, or hemoperitoneum. 90% of cases present as stage-one lesions; standard management is
to do unilateral oophorectomy and inspect peritoneal surfaces for implants. Particularly for women in
the reproductive years, the misdiagnosis of granulosa cell tumor as an undifferentiated carcinoma can
lead to inappropriate surgery. Granulosa cells can be recognized by the scant cytoplasm, relatively
uniform nuclear size and shape, and lack of well-organized epithelial structures. Cordlike patterns or
Call Exner bodies may, particularly in poorly executed frozen sections, lead to consideration of a poorly
differentiated carcinoma. Touch preps can be particularly helpful in evaluating a granulosa cell tumor,
as nuclear grooves and other cytologic features are much more readily seen in a touch preparation than on
Undifferentiated carcinoma of the ovary includes tumors with little or no differentiation towards the
traditional histologic subtypes. Patients tend to be older, with average age in the mid-fifties.
Approximately 50% of cases have bilateral ovarian involvement, and the majority present at an advanced
stage. Microscopically, undifferentiated carcinoma may present sheets of cells with scant cytoplasm and
deceptively uniform hyperchromatic nuclei, superficially resembling a granulosa cell tumor. Abortive
gland formation may be mistaken for sex cords or Cal Exner bodies. Pleomorphism, increased mitotic
activity atypical mitoses, and tumor necrosis not associated with torsion all suggest undifferentiated
carcinoma as opposed to granulosa cell tumor. Cytologic examination is particularly useful to compare
nuclear detail. The clinical history will generally separate these two diagnoses based on age,
bilaterality and stage at presentation: a granulosis cell tumor presenting at an advanced stage in an
older woman should be held suspect as a potential undifferentiated carcinoma.
Features of Granulosa cell tumor vs undifferentiated carcinoma
| ||Granulosa cell tumor ||Undifferentiated carcinoma|
|Age ||Peak 45-55 ||Peak 55-60|
|Stage ||90% stage I ||90% stage III or greater|
|Bilaterality ||5% ||50%|
|Gross ||Predominantly solid ||Predominantly solid|
|Low power ||Solid sheets, cords, usually no necrosis if no torsion ||Solid sheets, poorly formed papillae or glands, necrosis|
|High power ||Usually uniform nuclei, smaller, scant cytoplasm, grooves better seen on touch preps ||Pleomorphic, large nuclei scant cytoplasm|
|Mitoses ||Occasional, rarely atypical ||Frequent and atypical|
Case 13: Luteoma of Pregnancy
Ovarian lesions presenting in pregnancy reflect the tumors characteristic of the age group and the
special functional tumor-like lesions that arise during pregnancy. The incidence of adnexal masses
during pregnancy is variable, dependent of the use of imaging and the inclusion in studies of functional
lesions that involute without being biopsied. Retrospective studies have found adnexal masses in 1/632
and 1/1000 pregnancies.  The majority of benign lesions are mature cystic teratomas
(27% to50%), cystadenoma (20% to 34%) and functional lesions (13% to 18%). Of malignant or borderline
tumors, germ cell tumors (30-45%), borderline tumor (30% to 35%) cystadenocarcinoma (5% to 10%) and sex
cord stromal tumors (10-20%) predominate. Torsion with and without rupture is a common presentation of
adnexal tumors during pregnancy.
The differential of a solid eosinophilic lesion presenting in pregnancy includes luteoma of pregnancy,
corpus luteum of pregnancy, stromal hyperthecosis, stromal hyperplasia, steroid (lipid) cell tumor,
Leydig cell tumor, luteinized granulosa cell tumor, oxyphilic variant of clear cell carcinoma and
metastatic carcinoma with marked stromal luteinization. Clear cell carcinoma is rare before the age of
40, and has cystic and papillary structures. Metastatic carcinoma typically has stromal reaction and
epithelial islands in addition to the luteinized stoma cells. In terms of intraoperative management, the
separation of functional lesions from tumor is most important. Functional lesions such as luteoma and
luteal cysts require no surgery beyond wedge excision, and will involute after pregnancy.
Differential of ovarian tumors in pregnancy
| ||Luteoma ||Steroid cell tumor ||Granulosa cell tumor|
|Age ||20's to 30's ||40's to 50's ||20's to 70's|
|Race ||80% in African Americans ||No tendency ||No tendency|
|Laterality ||Multifocal or bilateral ||Unilateral ||Unilateral|
|Symptoms ||No symptoms or torsion ||Most are virilizing ||Hyperestrogenic|
|Histology ||Uniformly pink cells, rarely lipid vacuoles ||Pink and clear cells, lipid ||Solid, cords, trabeculae, may have vacuoles|
|Cytology ||Uniform nuclei, small nucleoli ||Variable nuclei, small nucleoli ||Nucleoli, but frequently grooves|
Case 14: Endometrial Carcinoma, Grade 3, Stage II B or Greater
The diagnosis of endometrial carcinoma is typically made on biopsy or curetting prior to surgery.
Intraoperative evaluation of hysterectomy specimens is done to document the extent of disease and tumor
grade so that a decision regarding pelvic lymph node dissection may be made. Features indicating a high
risk of metastasis are shown below. If no risk factors are present, there is a 2.8% risk of pelvic and
<1% risk of paraaortic node involvement
Prognostically significant features for endometrial carcinoma
|Feature ||Relative risk increase of lymph node metastasis|
|Serous or Clear cell histology ||3X|
|Grade 3 histology ||3X|
|Outer half myometrial involvement ||5X|
|Cervical involvement ||4X|
|Adnexal involvement ||4X|
Missing significant prognostic factors during the intraoperative examination leads to the omission of
pelvic node dissection, which usually leads to pelvic radiation therapy. Over diagnosis of bad
prognostic factors leads to unnecessary pelvic node dissection and increased potential for morbidity (up
The serosa and adnexa of the hysterectomy specimen are inspected grossly for extrauterine involvement,
which is rarely seen. The corpus is bivalved at 3 and 9 o'clock and the lining inspected. Bread-loafing
cuts at 5 mm intervals are then made to identify areas of possible myometrial invasion. The deepest
apparent focus is then frozen, ideally as a full thickness, or in a manner to preserve the overall depth
and total thickness measurements. Any mucosal abnormality in the lower uterine segment and endocervical
canal should also be frozen.
Accuracy of intraoperative assessment of grade is between 80% and 96%, with under-grading the common
and usually due to sampling error. Gross assessment of myometrial invasion alone is
difficult, particularly with high-grade tumors, and is overall probably no better than 70% accuracy. 
Most discrepancies in depth involve superficial lesions.
Case 15: Mucinous Cystadenocarcinoma
Ovarian masses are rarely removed with a previous study confirming malignancy; a solid and cystic
ultrasound appearance on ultrasound suggests malignancy but is correct only 25% of the time, and only a
quarter of stage I ovarian tumors have elevated serum markers. Apparently localized lesions and other
sites of involvement are found on staging in a quarter of cases.  Under-diagnosis leads to
under-staging, while over-diagnosis of malignancy may result in inappropriate loss of fertility.
Mucinous ovarian tumors present two clinical problems: are they benign, borderline or malignant; and
are they primary or metastatic? The evaluation of mucinous tumors is the largest source of discrepancy
in intraoperative examination of gynecologic specimens.
Lesions with one or few smooth walled
dominant cysts and no sold areas on gross examination prove to be benign more than 95% of the time, 
and do not require frozen section examination. Multiloculated and solid and cystic mucinous lesions
require frozen section, however gross inspection rarely indicates where to find the focal area of
borderline or malignant histology. Although adequate sampling for permanent sections requires one
section per centimeter of the largest diameter of the tumor, it is impractical to do more than one or two
frozen sections. The predictive value of the frozen section diagnosis is 95% for benign, 99% for
malignant, and 65% for borderline tumors.  Approximately a fourth of frozen section diagnoses of
borderline tumor will have carcinoma in the final pathologic sections. For this reason a diagnosis of
"at least borderline" is sometimes warranted.
Metastases to the ovary from the intestinal tract may mimic a primary ovarian mucinous carcinoma or
borderline tumor. Useful clinical and histologic features have been described recently by Lee and Young
Features of primary and metastatic mucinous tumors
| ||Primary ||Metastatic ||P value|
|Laterality ||Unilateral 95% ||Bilateral 60% to 75% ||<.0001|
|Microscopic surface involvement ||Absent ||79% ||<.0001|
|Nodular growth pattern ||Absent ||42% ||<.0003|
|Infiltrative invasive pattern ||16% ||91% ||<.0001|
|Small glands/ tubules ||12% ||94% ||<.0001|
|Expansile invasive pattern ||88% ||18% ||<.0001|
|Complex papillae ||60 ||8 ||.0004|
|Benign appearing areas ||76 ||36 ||.008|
|Borderline with atypia ||57 ||31 ||.035|
Laterality, growth pattern, gland size and complex papillae are all highly predictive; areas of benign
or borderline histology are not. The status of the other ovary and previous history of intestinal
carcinoma should be established at the time of the intraoperative consultation. All patients with
bilateral tumors or suspicious histology should have the gastrointestinal tract evaluated during the
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