33 year old woman with33 year old woman with33 year old woman with 33 year old woman with enlarging finger massenlarging finger mass

Los Angeles Society of Pathologists Los Angeles Society of Pathologists S OS OStephen OhStephen Oh

Department of PathologyDepartment of PathologyLACLAC--USC HospitalUSC HospitalLACLAC USC HospitalUSC HospitalNovember 13, 2007November 13, 2007

Clinical HistoryClinical Historyyy33 y/o pregnant female with a slow33 y/o pregnant female with a slow--growing mass growing mass on the left middle fingeron the left middle fingeron the left middle finger. on the left middle finger.

Seen in clinic on 3/07 while five months pregnant. Seen in clinic on 3/07 while five months pregnant. States mass has been enlarging rapidly since pregnancy.States mass has been enlarging rapidly since pregnancy.

Rapid growth over fiveRapid growth over five--month period month period (3/07 (3/07 8/07)8/07)

PMH: NonePMH: NonePSH CPSH C ti 2ti 2PSH: CPSH: C--section x 2section x 2All: NKDAAll: NKDAMeds: NoneMeds: NoneMeds: NoneMeds: None

August 2007

March 2007 August 2007

Physical exam:

•• No Lymphadenopathy of Axilla or Epicondylar regionsNo Lymphadenopathy of Axilla or Epicondylar regions•• Mass on Distal Phalanx of L MF, fungating, involves nailMass on Distal Phalanx of L MF, fungating, involves nail, g g,, g g,

Circumference: 12 cmCircumference: 12 cmLength: 4.5 cmLength: 4.5 cm

•• Mild Fluctuance on Ulnar aspectMild Fluctuance on Ulnar aspect•• Mild Fluctuance on Ulnar aspectMild Fluctuance on Ulnar aspect•• +TTP, Erythematous base+TTP, Erythematous base•• Sensation intact RDN/UDNSensation intact RDN/UDN

Pertinent Labs:Pertinent Labs:

WBC 7.5, Hgb 14.4, Hct 43.8, Plt 267WBC 7.5, Hgb 14.4, Hct 43.8, Plt 267BMP NLBMP NLBMP NLBMP NLAlk Phos: 90, AST 36, ALT 56, T. Protein 8.6, Alk Phos: 90, AST 36, ALT 56, T. Protein 8.6, Albumin 4.9Albumin 4.9UA: + Protein 30 mg/dLUA: + Protein 30 mg/dLUA: + Protein 30 mg/dLUA: + Protein 30 mg/dLPT/PTT: 12.2(0.92)/31.6PT/PTT: 12.2(0.92)/31.6ββ--HCG: NegativeHCG: NegativeCRP 5.8CRP 5.8Cx NegativeCx NegativePPD: 8x10 mmPPD: 8x10 mmPPD: 8x10 mmPPD: 8x10 mm

Gross FindingsGross Findingsgg(Left Middle Finger)(Left Middle Finger)

15.3 x 2.5 x 0.2 amputated finger15.3 x 2.5 x 0.2 amputated fingerLarge necrotic ulcerating hemorrhagicLarge necrotic ulcerating hemorrhagicLarge necrotic ulcerating hemorrhagic Large necrotic ulcerating hemorrhagic mass (7.5 x 5.5 x 3.2 cm)mass (7.5 x 5.5 x 3.2 cm)–– Hemorrhagic friable tan yellow tissueHemorrhagic friable tan yellow tissue–– Hemorrhagic friable tan yellow tissueHemorrhagic friable tan yellow tissue

Proximal resection margin free of tumorProximal resection margin free of tumor

PAS + Diastase

Differential???Differential???Differential???Differential???

Differential DiagnosisDifferential DiagnosisggClear cell sarcomaClear cell sarcomaEpithelioid sarcomaEpithelioid sarcomaEpithelioid sarcomaEpithelioid sarcomaSynovial sarcomaSynovial sarcomaPNET/Ewing sarcomaPNET/Ewing sarcomaPNET/Ewing sarcomaPNET/Ewing sarcomaRhabdomyosarcomaRhabdomyosarcomaHemangiopericytomaHemangiopericytomae a g ope cyto ae a g ope cyto aLeiomyosarcomaLeiomyosarcomaGlomangiosarcomaGlomangiosarcomaggMelanomaMelanomaAdnexal TumorsAdnexal TumorsPrimary CarcinomaPrimary Carcinoma

Vi iVimentin Cytokeratin

-Primary Carcinoma

-Adnexal Tumors

Epithelioid Sarcoma

-Clear Cell Sarcoma

-Melanoma-Epithelioid Sarcoma

MSA MyoD1MSA MyoD1-Rhabdomyosarcoma

-Leiomyosarcoma

-Hemangiopericytoma

SMA Desmin

COLIV CD34C 3

-PNET/Ewing Sarcoma

-Synovial Sarcomay

CD31 CD99

bcl2Ki67

ImmunohistochemistryImmunohistochemistryyyPositive(+Positive(+):):VimentinVimentin

Negative(Negative(--):):CytokeratinCytokeratinVimentinVimentin

MuscleMuscle--specific Actinspecific ActinSmooth muscle ActinSmooth muscle ActinCD34CD34

yyEMAEMACK5/6CK5/6DesminDesminCD34CD34

bclbcl--22DesminDesminMyoD1MyoD1SS--100100M lM l MARTMARTMelMel--MARTMARTChromograninChromograninCD31CD31vWFvWFFLIFLI--11CD45CD45CD45CD45CD99CD99

Differential DiagnosisDifferential DiagnosisggPNET/Ewing sarcoma PNET/Ewing sarcoma MelanomaMelanomaMelanoma Melanoma Clear cell sarcomaClear cell sarcomaEpithelioid sarcomaEpithelioid sarcomaEpithelioid sarcomaEpithelioid sarcomaSynovial sarcomaSynovial sarcomaPrimary Carcinoma Primary Carcinoma a y Ca c o aa y Ca c o aAdnexal TumorsAdnexal TumorsLeiomyosarcomaLeiomyosarcomayyRhabdomyosarcomaRhabdomyosarcomaGlomangiosarcomaGlomangiosarcomaHemangiopericytomaHemangiopericytoma

Final DiagnosisFinal DiagnosisFinal DiagnosisFinal Diagnosis

Malignant Glomus TumorMalignant Glomus TumorMalignant Glomus Tumor Malignant Glomus Tumor (Glomangiosarcoma)(Glomangiosarcoma)

HistoryHistoryGlomangiosarcomaGlomangiosarcomaGlomangiosarcomaGlomangiosarcoma

Lumley & Stansfeld Lumley & Stansfeld (1972)(1972) 24 yr old pt24 yr old pt

Malignant glomus tumor(?)Malignant glomus tumor(?)

Lumley JSP, Stansfeld AG Infiltrating glomus tumor f l li b B M d J 1972 1 484 485 (Fiof lower limb Br Med J 1972; 1: 484-485. (Figures

1,2)

Enzinger & WeissEnzinger & WeissAiba et al. (1988):Aiba et al. (1988):

GlomangiosarcomaGlomangiosarcomaGlomangiosarcomaGlomangiosarcomaarising in benign arising in benign glomus tumorglomus tumor

Aib M t l Gl i i lAiba, M et al. Glomangiosarcoma in a glomus tumor. an immunohistochemical and ultrastructural study. 1988 Cancer; 61: 1467-1471. (Figures 1,2)

Metastatic Glomangiosarcoma:Metastatic Glomangiosarcoma:B ith it t l (1997)B ith it t l (1997)–– Braithwaite et al. (1997)Braithwaite et al. (1997)

Multiple glomus bodies and glomangiosarcoma at Multiple glomus bodies and glomangiosarcoma at original excision siteoriginal excision site Braithwaite et al Malignant glomus tumor: a case report oforiginal excision siteoriginal excision site Braithwaite et al. Malignant glomus tumor: a case report of

widespread metastases in a patient with multiple glomus body hamartomas. Am J Surg Pathol 1996; 20: 233-238. (Figures 1,2,3,6)

V

SH Canals

AA

Microscopic FindingsMicroscopic FindingsH&EH&E::–– Glomus Cells: Round Glomus Cells: Round ++ Spindle cells (GABG), Spindle cells (GABG),

Mitotic figuresMitotic figures Nuclear atypia HypercellularityNuclear atypia HypercellularityMitotic figures,Mitotic figures, Nuclear atypia, HypercellularityNuclear atypia, Hypercellularity–– Blood vesselsBlood vessels–– ++ StromaStroma-- Hyalinized, myxoidHyalinized, myxoidy yy y

IHCIHC::–– Similar staining pattern to benign: Similar staining pattern to benign:

Positive: MSA & SMA (Weaker), Vimentin (More Intense)Positive: MSA & SMA (Weaker), Vimentin (More Intense)Negative: Keratin, Neural, Endocrine, Vascular, DesminNegative: Keratin, Neural, Endocrine, Vascular, DesminBasement membrane: Collagen IV, Reticulin, or PASBasement membrane: Collagen IV, Reticulin, or PAS--DD

–– Malignant: also bcl2, p53, inc. Ki67 (MIBMalignant: also bcl2, p53, inc. Ki67 (MIB--1) index*1) index*EMEM: :

F i fil t i t ti i lF i fil t i t ti i l–– Fewer microfilaments, pinocytotic vesicles, Fewer microfilaments, pinocytotic vesicles, Basal Lamina (incomplete)Basal Lamina (incomplete)

LocationGlomus TumorsGlomus Tumors::–– Hand (>50%)Hand (>50%)

Distal Phalanx, Palm, Wrist Distal Phalanx, Palm, Wrist

GlomangiosarcomaGlomangiosarcoma::–– Lower Extremity (75%)Lower Extremity (75%)–– Soft Tissue & SkinSoft Tissue & Skin, ,, ,

–– Soft Tissue & Skin (Other sites)Soft Tissue & Skin (Other sites)OtherOther: :

Lung/Mediastinum:Lung/Mediastinum:

Soft Tissue & Skin Soft Tissue & Skin (Other sites)(Other sites)

OtherOther: : –– Lungs/Mediastinum:Lungs/Mediastinum:–– Lung/Mediastinum:Lung/Mediastinum:

Inc. TracheaInc. Trachea–– GI Tract:GI Tract:

Stomach Small & Large BowelStomach Small & Large Bowel

Lungs/Mediastinum: Lungs/Mediastinum: Inc. Trachea Inc. Trachea

–– GI TractGI Tract–– GU Tract:GU Tract:Stomach, Small & Large BowelStomach, Small & Large Bowel

–– GU Tract:GU Tract:Kidney, Vagina, UterusKidney, Vagina, Uterus

–– Sellar regionSellar region

GU Tract:GU Tract:BladderBladder

–– Sellar regionSellar region–– BoneBoneSellar regionSellar region

–– Bone, Nerve, OrbitBone, Nerve, Orbit–– Head & Neck:Head & Neck:

Oral & Nasal MucosaOral & Nasal Mucosa

BoneBone–– Hand: 9 cases Hand: 9 cases

Oral & Nasal MucosaOral & Nasal Mucosa–– CoccyxCoccyx

Clinical FeaturesClinical FeaturesFrequencyFrequency(%)(%)

SXSSXS DurationDuration LocationLocation SizeSizeCmCm

GenderGenderAgeAge

B iB i P iP i 77 D l/ bQD l/ bQ 11 3 1 F M3 1 F MBenign Benign (Hand) >50%(Hand) >50%

PainPain 7 years 7 years (40 yr)(40 yr)

Dermal/subQDermal/subQ <1 <1 (3(3--4)4)

3:1 F:M3:1 F:M3030--50 yr50 yr

BenignBenign PainPain >7 years>7 years Dermal/subQDermal/subQ Skin<1Skin<1--33 M>FM>F(Other) ~25%(Other) ~25% Mass effectMass effect

OtherOther(20 yr)(20 yr) Internal organsInternal organs Deep >1Deep >1 4040--70 yr70 yr

(27(27--82 yr)82 yr)MultipleMultiple ++ PainPain VariableVariable Dermal/subQDermal/subQ <1<1--33 M>FM>Fpp(Benign) ~10%(Benign) ~10% (9.0)(9.0) ChildrenChildren

MalignantMalignant(Other) <5%(Other) <5%

PainPainMass effectMass effect

MonthsMonths--Years (9 yr)Years (9 yr)

Dermal/subQDermal/subQInternal organsInternal organs

Skin<1Skin<1--33Deep >1Deep >1

M>FM>F4040 70 yr70 yr(Other) <5%(Other) <5% Mass effectMass effect

OtherOtherYears (9 yr)Years (9 yr) Internal organs Internal organs Deep >1Deep >1 4040--70 yr70 yr

(20(20--84 yr)84 yr)MalignantMalignant(H d) <1%(H d) <1%

PainPain MonthsMonths--Years (18 yr)Years (18 yr)

Dermal/subQDermal/subQ <1<1--33(7 5)(7 5)

8:1 F:M8:1 F:M3030 7777(Hand) <1%(Hand) <1% Years (18 yr)Years (18 yr) (7.5)(7.5) 3030--77 yr77 yr

Gould et al (1990)Gould et al (1990) 33--way classificationway classificationGould et al.(1990)Gould et al.(1990) 33 way classification way classification systemsystem

Locally infiltrating “benign” glomus tumor (LIGT)Locally infiltrating “benign” glomus tumor (LIGT)Locally infiltrating benign glomus tumor (LIGT)Locally infiltrating benign glomus tumor (LIGT)

Glomangiosarcoma arising in benign glomus tumor Glomangiosarcoma arising in benign glomus tumor -Lumley & Stansfeld’s case

(GABG)(GABG)

Glomangiosarcoma arising de novo (GADN)Glomangiosarcoma arising de novo (GADN)- Enzinger & Weiss, Aiba et al’s case

Glomangiosarcoma arising de novo (GADN)Glomangiosarcoma arising de novo (GADN)-Braithwaite et al’s case

-Our Case(?)-Our Case(?)

SXSSXS D tiD ti L tiL ti SiSi S AS A T t t St tT t t St t

+ Benign component (GABG) Pure Sarcoma-like (GADN)Hand (n=9)

SXSSXS DurationDuration LocationLocation SizeSize SexAgeSexAge Treatment, StatusTreatment, StatusWetherington Wetherington et al. (1997) et al. (1997)

PainPain 1 Year1 Year ThumbThumb 0.5 cm0.5 cm F 30 yrF 30 yr Excision/ReexcisionExcision/ReexcisionAlive, no recurrenceAlive, no recurrence

Fuentes et al. Fuentes et al. (2005)(2005)

PainPain 1 Year1 Year Thenar Thenar 0.5 cm0.5 cm F 36 yrF 36 yr Excision/ReexcisionExcision/ReexcisionAlive, no recurrenceAlive, no recurrence

Gould et al. Gould et al. PainPain 1 Year1 Year Bet. 2Bet. 2ndnd & 3& 3rdrd 3 cm3 cm F 17 yrF 17 yr ExcisionExcision(1990) (1990)

aa eaea ee & 3& 3metacarpals metacarpals

3 c3 c yy c s oc s oAlive, no recurrenceAlive, no recurrence

Khoury et al. Khoury et al. (2005) (2005)

NoneNone 5 Months5 Months Base of Base of ThumbThumb

3 cm3 cm F 48 yrF 48 yr Excision/Reexcision Excision/Reexcision + Chemotherapy+ Chemotherapy( 005)( 005) ThumbThumb + Chemotherapy + Chemotherapy Mets to Lung (Alive)Mets to Lung (Alive)

Park et al. Park et al. (2003)(2003)

PainPain 5 Months5 Months PalmPalm 1.5 cm1.5 cm F 74 yrF 74 yr ExcisionExcisionAlive no recurrenceAlive no recurrenceAlive, no recurrenceAlive, no recurrence

?Our Case ?Our Case (2007)(2007)

PainPain 18 years18 years Third fingerThird finger(Distal tip)(Distal tip)

7.5 cm7.5 cm F 33 yrF 33 yr Ray AmputationRay AmputationAliveAlive

Folpe et al. Folpe et al. (2001)(2001)

?????? ?????????? Finger (2)Finger (2)Wrist (1)Wrist (1)

0.50.5--3 3 cmcm

2 F, 1 M2 F, 1 M3838--77 yr77 yr

ExcisionExcisionAlive, no recurrenceAlive, no recurrence

Khoury et al. Malignant Glomus Tumor: A case report and review of literature, focusing on its clinicopathologic features and immunohistochemical profile. 2005 Am J Dermatopathol; 27(5): 428-431. (Figure 4)

DE NOVO GLOMANGIOSARCOMA: DE NOVO GLOMANGIOSARCOMA: Total 14 cases, 3 recurrences, Total 14 cases, 3 recurrences, 5 metastases5 metastases, , 5 deaths5 deaths

Kreutz et al. M 33 Thigh (10 cm) Met. to Maxilla (Alive)Kreutz et al. M 33 Thigh (10 cm) Met. to Maxilla (Alive)Braithwaite et al. M 63 Nose (2 cm) Distant mets Braithwaite et al. M 63 Nose (2 cm) Distant mets (Died)(Died)W t b t l F 47 L ft hi (1 ) Di t t tW t b t l F 47 L ft hi (1 ) Di t t t (Di d)(Di d)Watanabe et al. F 47 Left hip (1 cm) Distant mets Watanabe et al. F 47 Left hip (1 cm) Distant mets (Died)(Died)Gaertner et al. M 69 Lung (9.5 cm) Distant metsGaertner et al. M 69 Lung (9.5 cm) Distant mets (Died)(Died)Shim et al. F 57 Bladder (6.5 cm) Distant mets Shim et al. F 57 Bladder (6.5 cm) Distant mets (Died)(Died)Choi et al. F 78 Mediastinum (4.5 cm) Local invasion Choi et al. F 78 Mediastinum (4.5 cm) Local invasion (Died)(Died)Gould et al. F 72 Cheek (5 cm) Local recurrence (Alive)Gould et al. F 72 Cheek (5 cm) Local recurrence (Alive)Gould et al. F 26 Back/Axilla (15 cm) (Alive)Gould et al. F 26 Back/Axilla (15 cm) (Alive)Hiruta et al. M 44 Right thigh (7 cm) (Alive)Hiruta et al. M 44 Right thigh (7 cm) (Alive)Matsumoto et al F 16 Brachial muscle (5 cm) (Alive)Matsumoto et al F 16 Brachial muscle (5 cm) (Alive)Matsumoto et al. F 16 Brachial muscle (5 cm) (Alive)Matsumoto et al. F 16 Brachial muscle (5 cm) (Alive)

GLOMANGIOSARCOMA ARISING IN BENIGN TUMOR: GLOMANGIOSARCOMA ARISING IN BENIGN TUMOR: Total 12 cases, 4 recurrences, Total 12 cases, 4 recurrences, 1 metastases1 metastases, ,, ,

Yu et al. M 47 Trachea (Size?) +Distant mets (Status?)Yu et al. M 47 Trachea (Size?) +Distant mets (Status?)

LOCALLY INFILTRATIVE GLOMUS TUMOR:LOCALLY INFILTRATIVE GLOMUS TUMOR:Total 5 cases, 2 recurrence, no metastases or deathsTotal 5 cases, 2 recurrence, no metastases or deaths

Atypical Glomus TumorsAtypical Glomus TumorsypypFolpe et al. (2001Folpe et al. (2001): New Criteria (n=52)): New Criteria (n=52)

MalignantMalignant::–– MalignantMalignant::Deep seated + Large size (>2 cm)Deep seated + Large size (>2 cm) or or Atypical MitosesAtypical Mitoses or or High nuclear grade + >5 mitoses/50 hpfHigh nuclear grade + >5 mitoses/50 hpf

–– Uncertain malignant potentialUncertain malignant potential::Superficial + >5 mitoses/50 hpf or Deep seated onlySuperficial + >5 mitoses/50 hpf or Deep seated onlySuperficial + >5 mitoses/50 hpf or Deep seated only Superficial + >5 mitoses/50 hpf or Deep seated only or Large size onlyor Large size only

–– SymplasticSymplastic::yyHigh nuclear grade onlyHigh nuclear grade onlyNo other malignant featuresNo other malignant features

Gl i t iGl i t i–– GlomangiomatosisGlomangiomatosis

Treatment & PrognosisTreatment & Prognosisgg

Surgical:Surgical:Surgical:Surgical:–– Complete excisionComplete excision

Adjuvant:Adjuvant:–– Chemotherapy and/or RadiotherapyChemotherapy and/or Radiotherapy

LongLong--term followterm follow--up:up:LIGT GABG: Local recurrence*LIGT GABG: Local recurrence*–– LIGT, GABG: Local recurrence*LIGT, GABG: Local recurrence*

–– GADN & Folpe: Local recurrence, Metastasis, DeathGADN & Folpe: Local recurrence, Metastasis, Death

*1 metastasis reported in the GABG group

SummarySummary--GlomangiosarcomaGlomangiosarcomayy ggLarger, DeepLarger, Deep--seatedseatedOld A M lOld A M lOlder Age, MalesOlder Age, Males

Hands: Still FemalesHands: Still Females

Indolent Course but….Indolent Course but….Local Recurrence & MetastasisLocal Recurrence & MetastasisClassification questionableClassification questionable

Difficult to diagnose Difficult to diagnose Round cell tumorsRound cell tumorsSpindle cell tumorsSpindle cell tumors

Clinical features nonClinical features non--specificspecific

FollowFollow--UpUpFollowFollow UpUp

Pt doing wellPt doing wellPt doing well.Pt doing well.No recurrence or metastatic disease.No recurrence or metastatic disease.N dj t thN dj t thNo adjuvant therapy.No adjuvant therapy.

AcknowledgementsAcknowledgementsAcknowledgementsAcknowledgements

Dr Paul Dinh Orthopedic Hand SurgeryDr Paul Dinh Orthopedic Hand SurgeryDr. Paul Dinh, Orthopedic Hand SurgeryDr. Paul Dinh, Orthopedic Hand SurgeryUSCUSC--LA County HospitalLA County Hospital

GlomangiosarcomaGlomangiosarcoma( 9)( 9)Hand (n=9)Hand (n=9)

++Benign component (GABGBenign component (GABG):):Benign component (GABGBenign component (GABG):):–– Wetherington et al. (1997) Wetherington et al. (1997) ThumbThumb–– Fuentes et al. (2005): Hypothenar eminence Fuentes et al. (2005): Hypothenar eminence ( ) yp( ) yp–– Gould et al. (1990)Gould et al. (1990) Between 2Between 2ndnd & 3& 3rdrd MetacarpalsMetacarpals

Pure SarcomaPure Sarcoma--like (GADNlike (GADN):):–– Khoury et al. (2005) Khoury et al. (2005) Base of thumbBase of thumb

Metastatic glomangiosarcomaMetastatic glomangiosarcoma

P k t l (2003)P k t l (2003) P lP l–– Park et al. (2003)Park et al. (2003) PalmPalm–– ?Our Case (2007) ?Our Case (2007) FingerFinger

OtherOther: Folpe et al (2001): Folpe et al (2001) 2 Finger 1 Wrist2 Finger 1 WristOtherOther: Folpe et al. (2001): Folpe et al. (2001) 2 Finger, 1 Wrist2 Finger, 1 Wrist