SPCSPC

骨科 住院醫師 楊碩文骨科 住院醫師 楊碩文骨科 李建和 主任骨科 李建和 主任

Basic DataBasic Data

劉 先生 劉 先生 64 y/o64 y/o

Chief Complain :Chief Complain :

Palpable a solid painless mass over Palpable a solid painless mass over right leg posterior aspect for 3 years right leg posterior aspect for 3 years and the mass rapid enlargement with and the mass rapid enlargement with pain for last 2 weeks pain for last 2 weeks

Present illnessPresent illness

Denied any systemic diseaseDenied any systemic disease Old open fracture of right tibia and fibula Old open fracture of right tibia and fibula

s/p external fixation 40+ years ago s/p external fixation 40+ years ago (fracture healed well)(fracture healed well)

Sustained a solid painless mass about one Sustained a solid painless mass about one egg size over right posterior leg for about egg size over right posterior leg for about 3 years3 years

No traumatic history at lesion area or No traumatic history at lesion area or infection sign and discharge sinusinfection sign and discharge sinus

The mass rapidly enlarged with pain and The mass rapidly enlarged with pain and tender for last 2 weeks tender for last 2 weeks

Physical ExaminationPhysical Examination

A solid, fixed, tumor mass with local A solid, fixed, tumor mass with local tenderness over right calf muscle tenderness over right calf muscle about 10x8x6 cm in sizeabout 10x8x6 cm in size

Right ankle weakness of Right ankle weakness of dorsiflexion ,no sensory disorderdorsiflexion ,no sensory disorder

Lab DataLab DataGlucose(Glucose( 血液血液 )) 118 mg/dl [70-99]118 mg/dl [70-99]

BUN (BUN ( 血液血液 ) ) 16.2 mg/dl [6.0-16.2 mg/dl [6.0-

20.0]20.0]

Creatinine(Creatinine( 血血) )

0.9 mg/dl [0.5-0.9 mg/dl [0.5-1.2]1.2]

eGFR eGFR 90 90 mL/min/1.73M2mL/min/1.73M2

GOT(GOT( 血液血液 ) ) 43 IU/L [<37]43 IU/L [<37]

CRP (CRP ( 血液血液 ) ) 1.40 mg/dL [<0.5]1.40 mg/dL [<0.5]

Na (Na ( 血液血液 ) ) 140 mEq/L [136-140 mEq/L [136-

145]145]

K (K ( 血液血液 ) ) 3.2 mEq/L [3.5-3.2 mEq/L [3.5-

5.1]5.1]

WBC WBC 8.93 10^3/uL [4.00-8.93 10^3/uL [4.00-11.00]11.00]

RBC RBC 4.17 10^6/uL [4.20-4.17 10^6/uL [4.20-6.10]6.10]

HGB HGB 14.3 g/dL [12.0-18.0]14.3 g/dL [12.0-18.0]

HCT HCT 41.4 % [37.0-52.0]41.4 % [37.0-52.0]

MCV MCV 99.3 fL [80.0-99.0]99.3 fL [80.0-99.0]

MCH MCH 34.3 pg [26.0-34.0]34.3 pg [26.0-34.0]

MCHC MCHC 34.5 g/dL [33.0-37.0]34.5 g/dL [33.0-37.0]

RDW RDW 12.7 % [11.5-14.5]12.7 % [11.5-14.5]

PLT PLT 316 x10^3 /uL [130-316 x10^3 /uL [130-400]400]

MPV MPV 8.90 fL [7.20-11.10]8.90 fL [7.20-11.10]

RDW-RDW-SD SD 45.8 fL45.8 fL

PDW PDW 9.5 fL9.5 fL

ImpressionImpression

r/o Soft tissue malignant tumor of r/o Soft tissue malignant tumor of right legright leg

Imaging studiesImaging studies Plain radiographs of the affected areaPlain radiographs of the affected area MRI with contrastMRI with contrast Chest CT scanChest CT scan

Biopsy was arranged and done on Biopsy was arranged and done on 100/07/25 100/07/25

Leiomyosarcoma of Leiomyosarcoma of extremity extremity

Leiomyosarcoma of Soft Tissue Leiomyosarcoma of Soft Tissue

Arise directly from the smooth Arise directly from the smooth muscle cells lining small blood muscle cells lining small blood vesselsvessels

Extremely rare occurrence Extremely rare occurrence Most malignant leiomyosarcomas Most malignant leiomyosarcomas

arise independently, and are not arise independently, and are not associated with benign tumors associated with benign tumors

Leiomyosarcoma of Cutaneous Leiomyosarcoma of Cutaneous Origin Origin

Man : women = 2:1Man : women = 2:1 First diagnosed (1-2 cm), and First diagnosed (1-2 cm), and

prognosis is generally good prognosis is generally good Deeper lesions can metastasize in up Deeper lesions can metastasize in up

to 30-40% of cases, usually to 30-40% of cases, usually hematogenously to the lungs hematogenously to the lungs

American Joint Committee on American Joint Committee on Cancer(AJCC) Staging SystemCancer(AJCC) Staging System

StagStagee

HistologicHistologicalalGradeGrade

SizeSizeLocation Location

(Relative to (Relative to fascia)fascia)

Systemic / Systemic / Metastatic Metastatic Disease PresentDisease Present

IAIA LowLow< <

5c5cmm

Superficial or Superficial or DeepDeep NoNo

IBIB LowLow≥ ≥

5c5cmm

SuperficialSuperficial NoNo

IIAIIA LowLow≥ ≥

5c5cmm

DeepDeep NoNo

IIBIIB HighHigh< <

5c5cmm

Superficial or Superficial or DeepDeep NoNo

IICIIC HighHigh≥ ≥

5c5cmm

SuperficialSuperficial NoNo

IIIIII HighHigh≥ ≥

5c5cmm

DeepDeep NoNo

IVIV AnyAny AnyAny AnyAny YesYes

Treatment Treatment

Surgery Surgery Achieving wide surgical margins is important in Achieving wide surgical margins is important in

preventing local recurrencepreventing local recurrence In this case: rescetable massIn this case: rescetable mass wild rescetion wild rescetion

Radiation Therapy Radiation Therapy Pre-operatively (neoadjuvant) or post-operatively Pre-operatively (neoadjuvant) or post-operatively

(adjuvant): (adjuvant): In this case: margin free, no consider R/TIn this case: margin free, no consider R/T

Chemotherapy Chemotherapy Treatment of metastatic disease Treatment of metastatic disease In this case: no sign of metastasis, no consider In this case: no sign of metastasis, no consider

C/TC/T

Prognosis: Soft Tissue Prognosis: Soft Tissue Leiomyosarcoma Leiomyosarcoma

worse prognosis :worse prognosis : age >62 years, size >4cm, tumor age >62 years, size >4cm, tumor

necrosis, vascular invasion, or previous necrosis, vascular invasion, or previous intralesional surgeryintralesional surgery

50% 3-year survival to 64% 5-year 50% 3-year survival to 64% 5-year survivalsurvival

Prognosis: Cutaneous Prognosis: Cutaneous Leiomyosarcoma Leiomyosarcoma

True intradermal leiomyosarcoma is True intradermal leiomyosarcoma is thought not to metastatsize thought not to metastatsize

Wide excision of truly intradermal Wide excision of truly intradermal tumors, if achievable, is curativetumors, if achievable, is curative

Bone scan

CT pre- & post-C

T1WI STIR T2WI

STIR

Gd-T1WI

GNSoleus

AT

PT

PL

EDL

No pulmonary meta.

case I 劉 x 慶 11806 xxxT11-9233, 9263

Frozen section and biopsy

Soft tissue, calf, right, intra-operative biopsy,

spindle cell tumor, favor sarcoma with myogenic

differentiation

T11-9983

Soft tissue, leg, right, wide excision, leiomyosarcoma

Frozen section: one tissue fragment measuring 1.6 x 0.7 x 0.7 cm in size neoplastic spindle cells arranged in sheet and fascicular pattern with lymphocyte

spindle cell tumor, favoring sarcoma

neoplastic spindle cells arranged in sheet and fascicular pattern with areas of necrosis

Neoplastic spindle cells with pleomorphic and blunt-ended nuclei

One part of calf muscle: 12.0 x 7.7 x 4.8 cm. and 240 gm. with an intramuscular tumor: 4.9 x 4.7 x 3.5 cm

A piece of skin 11.8 x 4.3 cm. One surgical scar measuring 2.5 cm in length

On section, the tumor is heterogeneous brown to yellow and soft with focal hemorrhage and necrosis

The tumor is located intramuscularly. The overlying skin is not involved. The tumor measures 0.4 cm, 3.8 cm, 4.0 cm, 3.9 cm and 2.2 cm away from the lateral, medial, deep, superior and inferior section margins of the specimen

Necrosis: red area (left side), central tumor, normal muscle (right side)

Hemorrhage and necrosis

Tumor area

Hemorrhage and necrosis

Thick-walled vessel Tumor cells with eosinophilic or clear cytoplasm

Lymphoplasma cell

Tumor cells with eosinophilic or clear cytoplasm and pleomorphic and blunt-ended nuclei

Tumor cells with eosinophilic or clear cytoplasm and pleomorphic nucleiSome lymphocyte and eosinophil infiltrate

Mitotic figure: 3/10 hpf

Atypical mitosis

Small separated tumor nodule is noted

Main tumor mass

Skin is free from the tumor

HEActin (+), h-caldesmon (+)

Desmin (+) Vimentin (+)

CK (F+) CD31(F+), CD34 (-)

Myogenin (-) S-100, HMB45 (-)

Findings and Differential diagnosis

Gross findings: heterogeneous brown to yellow and soft with focal hemorrhage and necrosis → malignancy (sarcoma)

Microscopic findings:

1. Perpendicularly oriented fascicles of spindle cells

2. Brightly eopsinophilic cytoplasm

3. Blunt-ended nuclei

4. Nuclear atypia

→myogenic differentiation

Immunostudy:

(+) Vimentin, Actin, Desmin, h-caldesmon

Focal (+): CK, CD31

(-): myogenin, S-100, HMB45, CD34

Spindle cell sarcoma, with myogenic differenitation

h-Caldesmon leiomyosarcoma (consultation with Dr. Hsuan-Ying Huang in Kaohsiung CGMH)

MICROSCOPICHistologic Type: LeiomyosarcomaFNCLCC (French Federation of Cancer Centers Sarcoma Group) grading

system:Tumor differentiation: Score 2: sarcomas of definite histologic typeMitotic count: Score 3: 20 or more than 20 mitoses per 10 HPF (our case: 22/10 hpf)Tumor necrosis: Score 1: less than or equal to 50 % tumor necrosis

Histological grade: Grade 3: total score 6 -8

Margins: Margins negative for sarcomaDistance of sarcoma from closest margin: 0.4 cm, lateral soft tissue

marginsLymph-Vascular Invasion: Not identified

Pathologic Staging (pTNM) (AJCC/UICC TNM, 7th edition)Primary Tumor (pT): pT1b: Tumor 5 cm or less in greatest dimension, deep tumorRegional Lymph Nodes (pN): pNX: Regional lymph nodes cannot be assessed (not sampled)

Anatomic stage/prognostic groups: pStage IIA at least (pT1b NX MX G3)

Stage IA T1a N0, NX M0 G1, GX

T1b N0, NX M0 G1, GX

Stage IB T2a N0, NX M0 G1, GX

T2b N0, NX M0 G1, GX

Stage IIA T1a N0, NX M0 G2, G3

T1b N0, NX M0 G2, G3

Stage IIB T2a N0, NX M0 G2

T2b N0, NX M0 G2

Stage III T2a, T2b N0, NX M0 G3

AnyT N1 M0 Any grade

Stage IV AnyT Any1 M1 Any grade

Leiomyosarcoma - 1

1. Definition: malignant neoplasm composed of cells exhibiting smooth muscle differentiation

2. Etiology: EB virus associated in immunosuppressed patient or associated with radiation

3. Incidence: Rare: 10-15% of extremity sarcoma (but common if including the uterine and visceral lesions)

4. Age: middle-aged adults5. Gender: no preference (women easily found in

retroperitoneal and inferior vena cava areas)

Leiomyosarcoma - 26. Classification:

a. leiomyosarcoma of soft tissueb. leiomyosarcoma of cutaneous originc. leiomyosarcoma of vascular origind. leiomyosarcoma in the immunocompromised hoste. leiomyosarcoma of bone

Variant and special forms: Myxoid leiomyosarcoma Inflammatory leiomyosarcoma

Pleomorphic leiomyosarcoma Leiomyosarcoma with osteoclastic-like giant cells Epitheliod leiomyosarcoma

Immunohistochemistry for leiomyosarcoma

• Desmin +• Actin-sm +• Calponin +• Caldesmon +• CK-PAN +• ER -• CD34 -• PR -• S-100 -• HMB-45 -

Leiomyosarcoma - 37. S/S: deep soft tissue mass – often asymptomatic

a. retroperitoneal – abdominal painb. vena cava →

Upper portion: Budd-Chari syndrome (hepatomegaly, jaundice, ascites) Mid-portion: Renal obstruction

Lower portion: lower extremity edema8. Treatment:

*surgical excision, radiation, chemotherapy9. Prognosis: depend on site and stages of lesions

a. Restricted in cutis → essentialy never meta. As “atypical smooth muscle tumor”b. in subcutis: up to 1/3 meta. 10-20% die of diseasec. retroperitoneum: 80% die of disease, typical with metastasisd. bone: up to ½ meta. 5 y survival: 65%e. vena cava: 5y – 50%, 10y – 30% survivalf. head and neck: over ½ metastasis

北醫附醫， 萬芳醫院， 雙和醫院 (1995-2011/6) (1998-2011/6) (2008-2011/6)

1. leiomyoma: 8313 Uterus: 8033 age:10-96 (average: 47.3)

2. leiomyosarcoma: 39 Uterus: 20 age: 35-67 (average:52.1) 20/8033: 0.24%

Non-Uterus: 23 age: 39-92 (mean: 69) M:F: 9:14

Intraabdomen-5, extremity-5, G-I-4, retroperitoneum-2, urinary bladder-2, back-1, pararectum-1, cervix-1, vagina-1, palate-1

1. leiomyoma: 423 Uterus: 355 age:17-82 (average: 47.6)

2. leiomyosarcoma: 3 Uterus: 0

Non-uterus: 3 age: 48-62 (mean:57.3) M:F: 2:1

extremity-1, retroperitoneum-1,

G-I-1

1. leiomyoma: 2161 Uterus: 1693 age:10-97 (average: 51.4)

2. leiomyosarcoma:12 Uterus: 3 age: 42-63 (average:51.3) 3/1693: 0.18%

Non-uterus: 9 age: 41-93 (mean:

58.2) M;F: 3:6 extremity-2, retroperitoneum-2, G-I-3, vagina-1, scrotum-1

SPC 100.08.26王樂明醫師 / 劉偉民主任

PATIENT PROFILE

Name: 楊 O 萍 Chart No.: 11767181 Gender: female Age: 61 years old Admitted data: 100.7.18

CHIEF COMPLAINT

Vaginal spotting for several weeks

PRESENT ILLNESS This is a 61-year-old female patient, with

history of 1) duodenal ulcer, 2) myoma uteri, found 10 years ago. Her OBS/GYN history as followed: 1)G0P0AA0, 2)LMP: menopause at 55 y/o, 3)menarche at 14 years old, 4)duration for 7 days, 5)interval at about 30 days. She found vaginal spotting recently, so she came to our OPD for medical consultation and ultrasound showed endometrium thickness of 13 mm with pelvic mass closed to posterior wall (63x64x68mm) of uterus. Under the impression of pelvic mass, she was admitted to our ward for further surgical intervention.

100.7.04

CA125 ( 血液 ) 12.21 U/ml [<35.00]

CBC (7/18) WBC: 6.75X103 /uL RBC: 4.36X106 /uL Hb: 13.2 g/dL MCV: 90.6 fL PT/aPTT: 12.2/33.2 GOT/GPT: 17/15 Na: 143 mEq/L Ca: /9.5 mg/dl K: 3.9 mEq/L Cl: 106 mEq/L

Endometrial hyperplasia: 13 mm

Pelvic mass: 83X64X68mm

Left ovary

Right ovary

CT

1. A fatty containing space-taking lesion in pelvis with abutting to uterus & no visible of ovaries ( possible due to age status), highly suggestive of dermoid cyst of ovary. Please correlate with clinical information. 2. bil. renal cysts 3. Several gallstones with focal adenomyosis of fundus

ARRANGED OPERATION

Laparoscopic assisted pelvic excision

One myomatous mass 8.0 x 7.7 x 5.8 cm in size and 200 gm in weight.On cut surface: white, yellow and elastic.No hemorrhage, myxoid and cystic changes

Hyalinized vessels

Hyalinized vessels

Spindle smooth muscle

Focal myxoid background

Findings and differential diagnosis

• Gross: intrauterine tumor with white-yellow and soft to elastic

• Micro: benign looking smooth muscle bundles and scattered clusters or diffuse large clear vaculated cell

• D/D:1. angiomyolipooma2. clear cell tumor metastasis

3. lipoleiomyma

Actin (+) S-100(+)

Ki 67(very low) P53 (-)

Final diagnosis

lipoleiomyoma

Lipoleiomyoma

1. A rare morphologic variant of uterine leiomyoma characterized by the presence of scattered islands of mature adipocytes within the smooth muscle neoplasm.

2. Histogenesis – controversial

3. Benign, case report: malignant transformed

Lipoleiomyoma of the uterus is a rare condition.

• A perusal of the English literature revealed approximately 140 cases.

• The adipose tissue of the present tumor was free from atypia, and no lipoblasts were seen.

• p53 was negative and Ki-67 labeling was very low. The MDM2 and CDK4, markers of well-differentiated liposarcoma, were negative.

The histogenesis of uterine LL is controversial.

1. Traditionally, the adipose tissue element of LL is thought to be derived from degeneration of leiomyoma.

2. Sieinski (Int J Gynecol Pathol 8 (1989), pp. 357–363 ) and Resta et al (Pathol Res Pract 190 (1994), pp. 378–383)

thought that LL arises from metaplasia (neometaplasia) of immature perivascular pluripotent mesenchymal cells.

3. Lin and Hanai (Acta Pathol Jpn 41 (1991), pp. 164–169) considered that the adipose tissue is derived from direct

metaplasia of the smooth muscle cells of leiomyoma.

4. Gentile et al (Pathologia 88 (1996), pp. 132–134) thought that LL is derived from multipotential undifferentiated

mesenchymal cells.

5. Shintaku (Pathol Int 46 (1996), pp. 498–502) showed a case of angiomyolipomatous LL with vascular proliferation and also demonstrated cases of ordinary LL. He suggested that LL is a spectrum of lipomyovascular tumors of the uterus and also suggested that adipose tissue is derived from lipomatous metaplasia of leiomyoma.

6. Aung et al (Pathol Int 54 (2004), pp. 751–758 ) reported that 6 of 17 cases of LL showed angiomyolipoma-like vascular proliferation. They showed that the Ki-67 labeling of smooth muscle element was 1.38%, that of adipose tissue was 1.17%, and that of normal myometrium was 0.76%. They thought that both elements are proliferative lesions rather than fatty degeneration. They also found that HMB45 was positive of certain LLs. In the present tumor also, the Ki-67–positive cells were seen in both elements; but HMB45 was negative. In the present study, Ki-67–positive cells are seen in 0.2% to 0.3% of both adipose tissue and muscular elements, suggesting that both elements have the capacity for cell proliferation and that both the adipose tissue and leiomyomatous tissue components in the present LL are neoplastic.

7. Uterine LL may be associated with metabolic diseases including hyperlipidemia, hypothyroidism, and diabetes mellitus

(Int J Gynecol Obstet 67 (1999), pp. 47–49 ) This suggests that changes in lipid metabolism after menopausal transition may play a role in the development of LLs. The current case did not show hypercholesterolemia, hypertriglycerolemia, and hyperglucosemia.

8. In the present case, hemoglobin A1c was normal; and no other metabolic diseases including hypothyroidism were recognized. The relationship between metabolic diseases and development of uterine LL remains to be elucidated.

In large studies, 18.8% of patients with the uterine LLs were associated with gynecologic malignancies that may originate from the uterus, cervix, or ovaries

(Pathol Int 54 (2004), pp. 751–758 ) and (Int J Gynecol Pathol 25 (2006), pp. 239–242) In the present case, no gynecologic malignancies were recognized.

Liposarcoma Arising in Uterine Lipoleiomyoma:

A Report of 3 Cases and Review of the Literature

AJSP: February 2011 - Volume 35 - Issue 2 - p 221–227

McDonald, Anna Greene MD*; Cin, Paola Dal PhD†; Ganguly, Aniruddha PhD*; Campbell, Sharon*; Imai, Yuki MD‡; Rosenberg, Andrew E. MD*; Oliva, Esther MD*

北醫附醫， 萬芳醫院， 雙和醫院 (1995-2011/6) (1998-2011/6) (2008-2011/6)

1. leiomyoma: 8313

Uterus: 8033

age:10-96

(average: 47.3)

2. lipoleiomyoma: 21

Uterus: 20

age: 43-77

(average: 56.9)

20/8033: 0.25%

1. leiomyoma: 423 Uterus: 355 age:17-82 (average: 47.6)2. lipoleiomyoma: 1 Uterus: 1 age: 52 (average: 52) 1/355: 0.28%

1. leiomyoma: 2161 Uterus: 1693 age:10-97 (average: 51.4)2. lipoleiomyoma: 4 Uterus: 4 age: 40-64 (average: 54.2) 4/1693: 0.24%