Mesenchymal Tumors of the UterusMesenchymal Tumors of the Uterus

Sigurd LaxSigurd Lax

Department of Pathology, Department of Pathology, General Hospital Graz West, Graz, AustriaGeneral Hospital Graz West, Graz, Austria

sigurd.lax@lkh-grazwest.at or sigurd.lax@medunigraz.atsigurd.lax@lkh-grazwest.at or sigurd.lax@medunigraz.at

PathologyPathology

Teaching Hospital of the Teaching Hospital of the Medical University GrazMedical University Graz

Mesenchymal Tumors of the Uterus Mesenchymal Tumors of the Uterus (WHO 2003)(WHO 2003)

• Smooth muscle tumorsSmooth muscle tumors

• Stromal tumorsStromal tumors

• Others Others

• More than 90% of uterine mesenchymal tumors are of smooth muscle differentiation

• Tumors of endometrial stromal differentiation are rare

• Basically all tumors may occur

Uterine smooth muscle tumorsUterine smooth muscle tumors

• Most frequent uterine neoplasmsMost frequent uterine neoplasms

• Leiomyoma (fibroids): 20-25% of womenLeiomyoma (fibroids): 20-25% of women

• Typical uterine corpus, less frequent cervix Typical uterine corpus, less frequent cervix

• Leiomyosarcomas sind most frequent uterine sarcomasLeiomyosarcomas sind most frequent uterine sarcomas

• Leiomyosarcomas of uterine cervix rareLeiomyosarcomas of uterine cervix rare

Uterine smooth muscle tumors Uterine smooth muscle tumors (WHO 2003)(WHO 2003)

• Leiomyosarcoma Leiomyosarcoma Variants (epitheloid, myxoid)Variants (epitheloid, myxoid)

• Smooth muscle tumors of uncertain malignant potential Smooth muscle tumors of uncertain malignant potential

• Leiomyoma Leiomyoma VariantsVariants

Abeler et al., Histopathology 2009

Uterine smooth muscle tumors: Uterine smooth muscle tumors: A diagnostic challengeA diagnostic challenge

• 12431 malignant uterine neoplasms in the Norwegian Cancer 12431 malignant uterine neoplasms in the Norwegian Cancer RegistryRegistry

• 4.7% sarcomas (587 cases) >>3.4% (419 cases)4.7% sarcomas (587 cases) >>3.4% (419 cases)

• 29% of diagnosis (168 cases) revised (WHO 2003 criteria)29% of diagnosis (168 cases) revised (WHO 2003 criteria)

Abeler et al., Histopathology 2009

What are the diagnostic problems of What are the diagnostic problems of uterine smooth muscle tumors?uterine smooth muscle tumors?

• Most tumors are not problematic: LeiomyomasMost tumors are not problematic: Leiomyomas

• Most sarcomas are not problematic but the diagnostic Most sarcomas are not problematic but the diagnostic criteria have changed criteria have changed

• Groups of uncertain biological behavior and limited Groups of uncertain biological behavior and limited experience, respectively (“Borderline”)experience, respectively (“Borderline”)

• Even in large studies number of cases within the Even in large studies number of cases within the problematic categories smallproblematic categories small

Change of criteria for malignancy for Change of criteria for malignancy for uterine smooth muscle tumorsuterine smooth muscle tumors

• Number of mitosis: >5/10 HPF Number of mitosis: >5/10 HPF

• Cellular atypia: “No atypia, no Cellular atypia: “No atypia, no sarcoma” (Henry J. Norris, 1993) sarcoma” (Henry J. Norris, 1993)

• Complex criteria “Stanford” (Bell et Complex criteria “Stanford” (Bell et al. 1994)al. 1994)

Problematic uterine smooth muscle neoplasmsProblematic uterine smooth muscle neoplasmsBell et al., AJSP 1994Bell et al., AJSP 1994

• 213 cases with > 2 years of follow up213 cases with > 2 years of follow up

• 5 groups according to mitosis, necrosis, atypia5 groups according to mitosis, necrosis, atypia

• Emphasis the importance of tumor cell necrosisEmphasis the importance of tumor cell necrosis

• Reduces the value of mitotic indexReduces the value of mitotic index

• Study is a mile stone but the number of cases in some Study is a mile stone but the number of cases in some groups small groups small

Problematic uterine smooth muscle neoplasmsProblematic uterine smooth muscle neoplasmsBell et al., AJSP 1994Bell et al., AJSP 1994

AtypiaAtypia TC-NecrosisTC-Necrosis MitosisMitosis ““Failure”Failure”

00 00 >5>5 0,5%0,5%

++ 00 <10<10 2%2%

++ 00 >10%>10% 40%40%

++ ++ anyany 75%75%

00 ++ >10>10 50%50%

FocalFocal 00 anyany 00

TCNTCN AtypiaAtypia MIMI DiagnosisDiagnosisPresent Diffuse moderate Diffuse moderate

to severeto severeanyany LeiomyosarcomaLeiomyosarcoma

No to mildNo to mild > 10> 10 LeiomyosarcomaLeiomyosarcoma

< 10< 10 LeiomyosarcomaLeiomyosarcoma (Differential diagnosis: (Differential diagnosis: acute infarction of leiomyoma, e.g after acute infarction of leiomyoma, e.g after torsion or submucosaltorsion or submucosal

Absent Diffuse moderate Diffuse moderate to severeto severe

> 10 > 10 LeiomyosarcomaLeiomyosarcoma

< 10 < 10 Atypical leiomyoma (low risk of recurrence)

No to mildNo to mild < 10< 10 Leiomyoma

> 10 > 10 Mitotically active leiomyoma

Focal moderate Focal moderate to severeto severe

< 15< 15 Leiomyoma Leiomyoma with limited experience with limited experience regarding the clinical courseregarding the clinical course

> 15 > 15 STUMPSTUMP

Blaustein, 2002

Algorithm for the diagnosis of Algorithm for the diagnosis of conventional smooth muscle tumors conventional smooth muscle tumors

(Robboy 2008)(Robboy 2008)

Criteria for the evaluation of uterine Criteria for the evaluation of uterine smooth muscle tumors (WHO 2003)smooth muscle tumors (WHO 2003)

• Cell typeCell type

• Cellular atypiaCellular atypia

• Type of necrosisType of necrosis

• Number of mitosisNumber of mitosis

• Behavior with respect to the surrounding tissueBehavior with respect to the surrounding tissue

• Vascular invasionVascular invasion

Cell TypeCell Type

• Usual (conventional) smooth muscle differentiationUsual (conventional) smooth muscle differentiation

• Epitheloid smooth muscle cellsEpitheloid smooth muscle cells

• Clear smooth muscle cells Clear smooth muscle cells

• Myxoid differentiationMyxoid differentiation

Moderate / Severe Cellular AtypiaModerate / Severe Cellular Atypia

• Pleomorphic Type: Pleomorphic Type: Nuclear polymorphism recognizable at low powerNuclear polymorphism recognizable at low power

• Uniform Type: Uniform Type: No nuclear polymorphism but remarkable chromatin changesNo nuclear polymorphism but remarkable chromatin changes

Smooth muscle tumors: Type of necrosis (WHO)Smooth muscle tumors: Type of necrosis (WHO)

Coagulative tumor cell necrosis

Infarction type necrosis (“hyaline necrosis”)

Abrupt transition from vital to necrotic tumor

Zone of fibrous tissue between vital and non-vital tumor

Shadows of necrotic cells No cell shadows visible

Bleeding and inflammation unusual

Bleeding usual

Smooth muscle tumors: Type of necrosisSmooth muscle tumors: Type of necrosis

(Robboy 2008)(Robboy 2008) Coagulative Coagulative HyalineHyaline

Borders Borders Abrupt Zonal

Blood vesselsBlood vessels Spared Involved

Nuclei Nuclei Most atypical, hyperchromatic

Pale

Outline Outline Complex, “geographic” Simple

Mitotic Index: Rules Mitotic Index: Rules (WHO 2003)(WHO 2003)

• EvaluationEvaluation per 10 HPF= high power fields= fields with per 10 HPF= high power fields= fields with 400x magnification (10x Okular, 40x Objektiv) 400x magnification (10x Okular, 40x Objektiv)

• Count areas with highest number of mitosis Count areas with highest number of mitosis • Count only unequivocal mitosis (Cave: inflammatory Count only unequivocal mitosis (Cave: inflammatory

cells, karyorrhexis)cells, karyorrhexis)• 4 sets of 10 HPF evaluated4 sets of 10 HPF evaluated• Cave: no standardized field (like for grading of breast Cave: no standardized field (like for grading of breast

carcinoma)!carcinoma)!

Conventional smooth muscle tumors: Criteria Conventional smooth muscle tumors: Criteria of malignancyof malignancy

• Any tumor cell necrosis.Any tumor cell necrosis.

• In the absence of tumo cell necrosis diffuse moderate to In the absence of tumo cell necrosis diffuse moderate to severe nuclear atypia and a mitotic index of ≥ 10 per 10 severe nuclear atypia and a mitotic index of ≥ 10 per 10 HPF erforderlich.HPF erforderlich.

• If the mitotic index is < 10 per 10 HPF low risk of If the mitotic index is < 10 per 10 HPF low risk of recurrence (< 2-3%) and late recurrence (atypical recurrence (< 2-3%) and late recurrence (atypical leiomyoma).leiomyoma).

Conventional smooth muscle tumorsConventional smooth muscle tumors

• Without tumor cell necrosis and significant Without tumor cell necrosis and significant

atypia benign even if mitotic index is high atypia benign even if mitotic index is high

(possibility of malignant course <<1% acc. to (possibility of malignant course <<1% acc. to

Bell et al., 1994).Bell et al., 1994).

Epithelioid and myxoid smooth muscle Epithelioid and myxoid smooth muscle tumorstumors

• Criteria for malignancyCriteria for malignancyAny tumor cell necrosisAny tumor cell necrosisIn the absence of tumor cell necrosis diffuse In the absence of tumor cell necrosis diffuse

moderate to severe nuclear atypia and mitotic index moderate to severe nuclear atypia and mitotic index of < 5 per 10 HPF.of < 5 per 10 HPF.

Uterine Leiomyosarcoma: Grading Uterine Leiomyosarcoma: Grading

• According to WHO no grading performedAccording to WHO no grading performed

• (Alternative: French Grading System for soft (Alternative: French Grading System for soft tissue sarcomas)tissue sarcomas)

Atypical LeiomyomaAtypical Leiomyoma

• Diffuse Atypia without tumor cell necrosis Diffuse Atypia without tumor cell necrosis • Mitotic index ≤10/10 HPFMitotic index ≤10/10 HPF• Benign course (1 malignant case in the Benign course (1 malignant case in the

literature)literature)• Low risk for recurrence after enucleation Low risk for recurrence after enucleation • Focal atypia: controversially discussed but Focal atypia: controversially discussed but

generally considered as benigngenerally considered as benign

Leiomyoma: Cases with limited Leiomyoma: Cases with limited experienceexperience

• According to WHO 2003 limited experience with:According to WHO 2003 limited experience with: focal moderate to severe atypia focal moderate to severe atypia > 15 mitosis per 10 HPF> 15 mitosis per 10 HPF

STUMPSTUMP

• Smooth muscle tumors of uncertain malignant potentialSmooth muscle tumors of uncertain malignant potential

• Criteria: Criteria: Possibility of a malignant tumor, e.g. due to poor clinical information wenig Possibility of a malignant tumor, e.g. due to poor clinical information wenig

klinische Info (some myxoid and epitheloid tumors)klinische Info (some myxoid and epitheloid tumors)

Uncertainty of cell typeUncertainty of cell type

Uncertainty of mitotic index Uncertainty of mitotic index

Uncertainty of type of necrosisUncertainty of type of necrosis

• But: Even world experts don‘t know what STUMPS areBut: Even world experts don‘t know what STUMPS are

• Thus: You should not use it too often, if everThus: You should not use it too often, if ever

Leiomyosarcoma with MetastasesLeiomyosarcoma with MetastasesJones&Norris, IJGP 1995Jones&Norris, IJGP 1995

• 28 cases, Follow up 1 month -13 years28 cases, Follow up 1 month -13 years

• Size 3-14 cm (median 8.5 cm)Size 3-14 cm (median 8.5 cm)

• Age 20-84 years (median 52 years)Age 20-84 years (median 52 years)

• Mitosis <3 - 41/10 HPF (median 22)Mitosis <3 - 41/10 HPF (median 22)

• Atypia ++ or +++ in 27/28 patientsAtypia ++ or +++ in 27/28 patients

• Coagulative tumor cell necrosis in 22/28 patientsCoagulative tumor cell necrosis in 22/28 patients

• Cell type: 10 epithelioid, 2 myxoid, 16 conventionalCell type: 10 epithelioid, 2 myxoid, 16 conventional

Leiomyosarcoma with Metastases Leiomyosarcoma with Metastases Jones&Norris, IJGP 1995Jones&Norris, IJGP 1995

• Important criteria Important criteria Age >50 (in 79%)Age >50 (in 79%)

Size >5 cm (in 79%)Size >5 cm (in 79%)

Atypia (++/+++)Atypia (++/+++)

Tumor cell necrosisTumor cell necrosis

Epithelioid cell type (even with low mitotic index and Epithelioid cell type (even with low mitotic index and without tumor cell necrosis)without tumor cell necrosis)

Leiomyosarcoma with Metastases Leiomyosarcoma with Metastases Jones&Norris, IJGP 1995Jones&Norris, IJGP 1995

• 6 metastasizing tumors <5 cm 6 metastasizing tumors <5 cm 5 tumors with tumor cell necrosis, 3 of which with increased 5 tumors with tumor cell necrosis, 3 of which with increased

mitotic index and ++/+++ atypiamitotic index and ++/+++ atypia1 tumor with + atypia and without tumor cell necrosis, but 1 tumor with + atypia and without tumor cell necrosis, but

with invasive growth and angioinvasion with invasive growth and angioinvasion

Leiomyosarcoma with Metastases Leiomyosarcoma with Metastases Jones&Norris, IJGP 1995Jones&Norris, IJGP 1995

• 6 metastasizing tumors <50 years of age6 metastasizing tumors <50 years of age4 tumors >5cm4 tumors >5cm4 tumors with ++/+++ atypia and tumor cell necrosis 4 tumors with ++/+++ atypia and tumor cell necrosis 1 tumors with ++/+++ atypia and 10 MF/10 HPF1 tumors with ++/+++ atypia and 10 MF/10 HPF1 tumors with + atypia and without tumor cell necrosis, but 1 tumors with + atypia and without tumor cell necrosis, but

with invasive growth and angioinvasionwith invasive growth and angioinvasion

Prognostic Factors of Uterine SarcomasPrognostic Factors of Uterine SarcomasAbeler et al., Histopathology 2009Abeler et al., Histopathology 2009

Sarcoma TypeSarcoma Type Prognostic FactorsPrognostic Factors

LeiomyosarcomaLeiomyosarcoma Tumor size + MitoseindexTumor size + Mitoseindex

ESSESS Mitotic index + Tumor cell Mitotic index + Tumor cell necrosisnecrosis

AdenosarcomaAdenosarcoma Tumor cell necrosisTumor cell necrosis

Undifferentiated SarcomaUndifferentiated Sarcoma AngioinvasionAngioinvasion

Leiomyosarcoma of the Uterus: Risik groups from Tumor Size and Mitotic CountLeiomyosarcoma of the Uterus: Risik groups from Tumor Size and Mitotic Count

Abeler et al., Histopathology 2009

Low: ≤10 cm and ≤10MF

Medium: >10 cm or >10 MF

High: >10 cm and >10 MF

LMS: Importance of Optimal Surgical Tumor Reduction

Dinh et al. 2004Dinh et al. 2004

Uterine smooth muscle tumors and p53 Uterine smooth muscle tumors and p53 MutationsMutations

• P53 Mutations frequent in leiomyosarcomasP53 Mutations frequent in leiomyosarcomas

• P53 immunoreactivity predictive for survivalP53 immunoreactivity predictive for survival

• No presence in leiomyomaNo presence in leiomyoma

• but: no data for cases of uncertain malignant but: no data for cases of uncertain malignant

potentialpotential

Immunohistochemistry for the diagnosis of Immunohistochemistry for the diagnosis of uterine mesenchymal tumors uterine mesenchymal tumors

• General rule:General rule:Panel of CD 10, desmin, caldesmon recommendedPanel of CD 10, desmin, caldesmon recommendedCD10 always positive in stromal tumors CD10 always positive in stromal tumors Caldesmon, desmin always positive in smooth Caldesmon, desmin always positive in smooth

muscle tumorsmuscle tumorsSMA not useful, also expressed in stromal tumorsSMA not useful, also expressed in stromal tumors

Immunohistochemistry for the diagnosis of Immunohistochemistry for the diagnosis of uterine mesenchymal tumorsuterine mesenchymal tumors

• Exceptions:Exceptions:CD 10 also positive in smooth muscle tumors, in particular in CD 10 also positive in smooth muscle tumors, in particular in

leiomyosarcomasleiomyosarcomas

• Desmin rarely positive in stromal tumorsDesmin rarely positive in stromal tumors

• Literature: Oliva et al. AJSP 2002; McCluggage Literature: Oliva et al. AJSP 2002; McCluggage Histopathology 2001 Histopathology 2001

ImHC and Biological BehaviorImHC and Biological BehaviorLee C-H et al., Mod Pathol 2009Lee C-H et al., Mod Pathol 2009

• Ki-67>10%, p53/p16 Ki-67>10%, p53/p16 ≥50%:≥50%: evidence for malignancyevidence for malignancy

• Positivity of 1 marker in 92% of Positivity of 1 marker in 92% of sarcomas and 2% of myomassarcomas and 2% of myomas

Pathology Report: Important informationsPathology Report: Important informations

• Size Size

• Tumor cell necrosis Tumor cell necrosis

• Degree of atypiaDegree of atypia

• Extension of the tumor (invasion of extrauterine tissue) Extension of the tumor (invasion of extrauterine tissue)

• Vascular invasionVascular invasion

• Mitotic indexMitotic index

• TNM classificationTNM classification

FIGO/UICC 2009: Leiomyosarcoma & ESSFIGO/UICC 2009: Leiomyosarcoma & ESS

StageStage pTNMpTNM DefinitionDefinition

II Tumor limited to the uterusTumor limited to the uterus

IAIA pT1apT1a < 5 cm diameter< 5 cm diameter

IBIB pT1bpT1b > 5 cm diameter> 5 cm diameter

IIII Tumor extends to pelvic tissueTumor extends to pelvic tissue

IIAIIA pT2apT2a Extension to adnexaeExtension to adnexae

IIBIIB pT2bpT2b Extension to extrauterine pelvic tissueExtension to extrauterine pelvic tissue

IIIIII Invasion abdominal tissue (not protrusion into the abdomen)Invasion abdominal tissue (not protrusion into the abdomen)

IIIAIIIA pT3apT3a 1 site1 site

IIIBIIIB pT3bpT3b >1 sites>1 sites

IIICIIIC pN1pN1 Metastases in pelvic and/or para-aortic lymph nodesMetastases in pelvic and/or para-aortic lymph nodes

IVIV Invasion of urinary bladder and/or rectum; distant metastases Invasion of urinary bladder and/or rectum; distant metastases

IVAIVA pT4pT4 Invasion of urinary bladder and/or rectumInvasion of urinary bladder and/or rectum

IVBIVB pM1pM1 Distant metastasesDistant metastases

Differential Diagnosis of Uterine Differential Diagnosis of Uterine Smooth Muscle TumorsSmooth Muscle Tumors

• Stromal tumorsStromal tumors

• Mixed smooth muscle and stromal tumorsMixed smooth muscle and stromal tumors

• UTROSCTUTROSCT

• PEComaPEComa

Endometrial Stromal Tumors Endometrial Stromal Tumors (WHO 2003)(WHO 2003)

• Stromal nodule Stromal nodule

• Endometrial stromal sarcoma (low grade) (ESS) Endometrial stromal sarcoma (low grade) (ESS)

• Undifferentiated sarcomaUndifferentiated sarcoma

High grade / low gradeHigh grade / low grade

Undifferentiated sarcomaUndifferentiated sarcoma ESS / Stromal noduleESS / Stromal nodule

ESS / undifferentiated SarcomaESS / undifferentiated SarcomaESSESS Undifferentiated Undifferentiated

SarcomaSarcoma

CytologyCytology monomorphousmonomorphous highly atypical, often highly atypical, often polymorphicpolymorphic

Growth patternGrowth pattern InfiltrativeInfiltrative Expansile Expansile

Vascular Vascular growthgrowth

Intravascular Intravascular growthgrowth

Vascular invasionVascular invasion

AgeAge 50-5550-55 70-8070-80

Course and Course and prognosisprognosis

Good, late Good, late recurrencerecurrence

Poor, early recurrence, Poor, early recurrence, frequent metastases frequent metastases

EstrogenEstrogen Estrogen-related Estrogen-related (ER positive)(ER positive)

Not estrogen-related (ER Not estrogen-related (ER negative)negative)

DiagnosisDiagnosis needs HE specimenneeds HE specimen on curettageon curettage

ESS: Growth patternESS: Growth pattern

• Diffuse enlargement of the myometriumDiffuse enlargement of the myometrium

• Nodular tumor massNodular tumor mass

• Infiltration of myometrium by mutlitple small nodules Infiltration of myometrium by mutlitple small nodules

Diagnostic ProblemDiagnostic Problem

• Differential diagnosis from leiomyomatosis or Differential diagnosis from leiomyomatosis or leiomyoma in frozen section, in particular in the setting leiomyoma in frozen section, in particular in the setting of extrauterine growth of extrauterine growth

Metaplastic Changes in Stromal TumorsMetaplastic Changes in Stromal Tumors

• Myogenic, chondroid, Myogenic, chondroid, osteogenic and osteogenic and lipomatous lipomatous differentiation differentiation

Sex cord Differentiation Sex cord Differentiation

• In ESS and ESNIn ESS and ESN

• Inhibin, CD 99, Inhibin, CD 99, calretinin positivecalretinin positive

• CD 10 may be negativeCD 10 may be negative

• DD: sex cord like tumor DD: sex cord like tumor of the uterus of the uterus (UTROSCT) (UTROSCT)

Undifferentiated Sarcoma of the Undifferentiated Sarcoma of the Endometrium (WHO)Endometrium (WHO)

• Definition: Definition: A high grade endometrial sarcoma that lacks specific A high grade endometrial sarcoma that lacks specific

differentiation and bears no histological resemblance to differentiation and bears no histological resemblance to endometrial stromaendometrial stroma

Resemblance to sarcomatous component in carcinosarcoma Resemblance to sarcomatous component in carcinosarcoma (ruled out by sampling) (ruled out by sampling)

• No comment on immunohistochemistry No comment on immunohistochemistry

Low/High grade/undifferentiated Low/High grade/undifferentiated Endometrial Sarcoma Dilemma Endometrial Sarcoma Dilemma

• Some investigators distinguish between low und high Some investigators distinguish between low und high grade endometrial stromal sarcoma, others do notgrade endometrial stromal sarcoma, others do not

• WHO: “all inclusive endometrial stromal”WHO: “all inclusive endometrial stromal”

• Thus, no reliable data, in particular for undifferentiated Thus, no reliable data, in particular for undifferentiated sarcoma sarcoma

• Undifferentiated sarcoma with / without Undifferentiated sarcoma with / without immunohistochemistry?! immunohistochemistry?!

Molecular Pathology of Uterine Stromal Molecular Pathology of Uterine Stromal Tumors Tumors

Kurihara et al. AJSP 2008Kurihara et al. AJSP 2008

ESSESS UESUES

JAZF1-JJAZ1 FusionJAZF1-JJAZ1 Fusion FrequentFrequent RareRare

P53 MutationsP53 Mutations No No FrequentFrequent

Estrogen receptorsEstrogen receptors Almost alwaysAlmost always Rare Rare

FIGO/UICC 2009: AdenosarcomaFIGO/UICC 2009: AdenosarcomaStageStage pTNMpTNM DefinitionDefinition

II Tumor limited to the uterus

IAIA pT1apT1a Limited to endometrium or endocervix, no myometrial invasion

IBIB pT1bpT1b Invasion into inner half of the myometrium

ICIC pT1cpT1c Invasion into outer half of the myometrium

IIII Extension beyond the uterus within the pelvis

IIAIIA pT2apT2a Extension to adnexae

IIBIIB pT2bpT2b Involvement of other pelvic tissue

IIIIII Invasion of abdominal tissues (not protrusion into the abdomen)

IIIAIIIA pT3apT3a 1 Localisation

IIIBIIIB pT3bpT3b >1 Localisation

IIICIIIC pN1pN1 Metastases in pelvic and/or para-aortic lymph nodes

IVIV Tumor invasion of bladder and/or rectum; distant metastases

IVAIVA pT4pT4 Tumor invasion of bladder and/or rectum

IVBIVB pM1pM1 Distant metastases

Immunohistochemistry: Antibody PanelImmunohistochemistry: Antibody Panel

• CD 10CD 10• DesminDesmin• CaldesmonCaldesmon• Ki-67 Ki-67 • CKCK• CalretininCalretinin• CD99CD99• InhibinInhibin• Melan A, HMB 45Melan A, HMB 45• Estrogen- and Progesterone receptorsEstrogen- and Progesterone receptors