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