non-epithelial tumors uterine tumors - iop pathology/… · · 2015-04-06muscle tumor s08-17284of...

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DEPARTMENT OF PATHOLOGYFACULTY OF MEDICINE SIRIRAJ HOSPITAL MAHIDOL UNIVERSITY

Non-epithelial Uterine Tumors

Tuenjai Chuangsuwanich, M.D.Department of Pathology, Faculty of Medicine Siriraj Hospital, Mahidol University.

20-02-10


Scope• Pure mesenchymal tumors

‐ Smooth muscle tumors‐ Endometrial stromal tumors

‐ Mixed endometrial stromal and smooth muscle tumor

• Mixed Mullerian tumors

• Miscellaneous ‐ Perivascular epithelioid cell tumor

‐ Adenomatoid tumor


Smooth muscle tumors

• Leiomyoma and leiomyoma variants

• Leiomyosarcoma

• Borderline smooth muscle tumor/ Smooth muscle tumor of uncertain malignant potential (STUMP)

DEPARTMENT OF PATHOLOGYFACULTY OF MEDICINE SIRIRAJ HOSPITAL MAHIDOL UNIVERSITYLeiomyoma

Enlarged nodular uterus

Cut surface: Well circumscribed, firm or rubbery, grey white mass (es) with whorled appearance.

Can be “shelled out”

Micro: Interlacing fascicles of uniform spindle cells with bland looking cigar-shaped nuclei. Mitosis is rare. Necrosis is absent.

S08-17284

Malee M.D.


Leiomyoma, histological variants

• Leiomyoma‐ with degenerative changes‐ with hydropic change‐ with hormonal induced changes (hemorrhagic/apoplectic)

• Cellular and highly cellular leiomyoma• Cellular and highly cellular leiomyoma• Mitotically active leiomyoma• Epithelioid leiomyoma• Myxoid leiomyoma • Leiomyoma with bizarre nuclei(Atypical leiomyoma, symplastic

leiomyoma)• Lipoleiomyoma

Leiomyoma with degenerative changes

M id h

hormonal induced changes (red degeneration/ hemorrhagic/apoplectic,)

Hydropic and cystic changeMyxoid change

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Cellular and highly cellular leiomyoma

Nucci MR, Oliva E. Gynecologic pathology.China: Churchill Livingstone; 2009

Epithelioid leiomyoma

Nucci MR, Oliva E. Gynecologic pathology. China: Churchill Livingstone; 2009


Leiomyoma with bizarre nuclei(Atypical leiomyoma)

1A4

Lipoleiomyoma


Leiomyoma, growth pattern variants

• Diffuse leiomyomatosis

• Dissecting leiomyoma including cotyledonoid leiomyoma

• Intravenous leiomyomatosis

• Diffuse leiomyomatosis peritonealis

• Leiomyoma with vascular invasion

• Benign metastasizing leiomyoma

Diffuse leiomyomatosis

Robboy J, Mutter GL, Prat J,Bently RC,Russel P, Anderson MC.Robboy’s pathology of the female reproductive tract. 2nd ed. 2009

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Dissecting leiomyoma includingcotyledonoid leiomyoma


Diffuse leiomyomatosis peritonealis



Intravenous leiomyomatosis


Leiomyosarcoma

‘Malignant smooth muscle tumor’• 1% of all uterine malignancies

• 0.64 cases per 100,000 women

• present later in life around or aftermenopause • unsuspected or presumed to be leiomyoma before patho. exam.


Leiomyosarcoma

Macro:- intramural , usually not associated with leiomyoma- average 8 cm , fleshy, poorly defined margins

Hemorrhage and necrosis



Micro:• Atypia• Mitotic figure……Atypical mitosis

Leiomyosarcoma

• Necrosis: geographic coagulation necrosis• Cellularity• Infiltrative pattern• Vascular invasion• Metastasis

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DEPARTMENT OF PATHOLOGYFACULTY OF MEDICINE SIRIRAJ HOSPITAL MAHIDOL UNIVERSITYLeiomyosarcoma

Frequent mitosishypercellularityAtypia

InfiltrativenessNecrosis


Necrosis

Complex/ geographicSharp outline

Atypical nuclei in necrotic areaSpared vessels

Tumor/ geographic necrosis

Robboy J,et al. Robboy’s pathology of the female reproductive tract. 2nd ed. 2009


• Types of leiomyosarcoma

‐ Conventional, spindle, NOS

E ith li id

Leiomyosarcoma

‐ Epithelioid‐Myxoid


Conventional LMS

DDx- Mitotically active leiomyoma - Apoplectic leiomyoma- Leiomyoma with bizarre nuclei- Highly cellular leiomyoma- Myxoid leiomyoma


Soft grey gelatinous surface, maybe well defined margin grosslyhypocellular, minimal atypialow mitotic count( mitotic count ≥ 2/10HPF..

myxoid LMS)

Myxoid leiomyosarcoma

Differential diagnoses:‐myxoid LM‐ hydropic LM‐myxoid EST‐ intravenous leiomyomatosis


Epithelioid leiomyosarcoma

• .. Round to polygonal cells in > 50% of tumor‐ Softer may lack whorled cut surface

‐ Eosinophilic/clear cytoplasm

‐ Round nuclei

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Epithelioid leiomyosarcoma

-Any degree of cytologic artypia and ≥5 mf /10HPFs without necrosis- ≥5 mf /10HPFs without necrosis with necrosis with any degree of cytologic atypia

AE1/AE3


DDx- Poorly differentiated carcinoma

- PEComa

Epithelioid LMS

- PEComa- UTROSCT- PSTT /ETT- Endometrial stromal sarcoma

- Malignant melanoma/ alveolar soft part sarc/ rhabdoid tumor


Borderline smooth muscle tumor / Smooth muscle tumor of uncertain malignant potential

(STUMP)]

• Smooth muscle tumors that are difficult to classify as benign or malignant based on generally applied criteriacriteria‐ Subtype of smooth muscle differentiation in

doubt…standard/epithelioid/myxoid

‐ Type of necrosis…uncertain‐ Borderline number of mitotic figures

These interpretation will result in different criteria of justifying malignancy.


Practical classification of smooth muscle tumors

Diagnosis Necrosis mf/10hpf Atypia

Leiomyosar ‐coma

+

‐

Any rate

>10

+ or ‐

Diffuse/ multifocal;moderate to severe

STUMP Questionable

‐‐

Any rate>15

Approaching but<10

+ or ‐

None

Diffuse/multifocal;moderate to severe

LM with bizarre nuclei

‐ ≤10 Diffuse/ multifocal;moderate to severe

Mitotically active LM

‐ ≤15 ‐


Immunohistochemistry

• Smooth muscle markers:(variable in LMS)‐ smooth muscle actin, desmin, smooth muscle myosin, h‐caldesmon‐ oxytocin, keratin, EMA (more often epithelioid variant)

bl

Smooth muscle tumor

‐ CD10 variable positivity‐ ER, PR in nearly 100%‐ AR in 30%‐WT‐1

p53 minimal to absent in benign

MiB-1( Ki-67)

DEPARTMENT OF PATHOLOGYFACULTY OF MEDICINE SIRIRAJ HOSPITAL MAHIDOL UNIVERSITYSmooth muscle markers

Smooth muscle actin,1A4 Desmin

h-caldesmon

Smooth muscle markers

Crum CP, Lee KR. Diagnostic gynecologic and obstetric pathology. 2006

Smooth muscle myosin heavy chain

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Endometrial stromal tumors(EST)‐ Compose of cells morphologically resemble

nonneoplastic proliferative phase endometrial stroma and prominent spiral arteriole‐like vascular component.

Cytogenetic abnormalities in low grade ESS chromosome rearrangements involving chromosomes 6,7 and 17/ most common reciprocal balanced ptranslocation:‐ t(7;17)(p15;q21) …( chimeric JAZF1‐JJAZ1 mRNA transcripts)

WHO 2003 Classification:‐ endometrial stromal nodule‐ endometrial stromal sarcoma, low grade‐ undifferentiated endometrial sarcoma


Endometrial stromal nodule(ESN)

• Very rare; median age, 47;AUB ;pelvic pain

• Macro: Well delineated, soft tan yellow cut surface, expansile margin; mean diameter,7 cm; intramyometrial, subserosal,

l idpolypoid

• Micro: Endometrial stromal cells and prominent spiral arteriole‐like vascular component;

‐ hypercellular/hypocellular/myxoid/epithelioid;

‐mf 1‐5/10HPFs.Focal irregularity not exceed 3 mm; no vascular invasion


Endometrial stromal nodule

Crum CP, Lee KR. Diagnostic gynecologic and obstetric pathology. 2006


- focal irregularities not exceeding 3 mm ; smooth muscle metaplasia at the periphery. (Mitotic figures=1-2/10 HPFs. - diffuse CD10(+), focal 1A4, and smooth muscle myosin heavy chain(+) in the tumor and thperipheral area; - diffusely (-)desmin. No angiolymphatic invasion


Mixed endometrial stromal and smooth muscle tumor

• Stromomyoma.. an admixture of endometrial stromal and smooth muscle elements…….a minimum of 30% f h i30% of the minor component

• Should be evaluated and reported in the same way as EST


Mixed endometrial stromal and smooth muscle tumor

CD10 Desmin 1A4

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Endometrial stromal sarcoma, low grade

• Macro‐ intramyometrial nodular mass

‐ intracavitary polypoid mass

‐ diffuse myometrial invasion

‐ any combination of these patterns

Extension beyond uterus/extensive

involvement of parametrial vessels(‘worm‐like’ appearance)

DEPARTMENT OF PATHOLOGYFACULTY OF MEDICINE SIRIRAJ HOSPITAL MAHIDOL UNIVERSITYEndometrial stromal sarcoma, low grade


Endometrial stromal sarcoma, low grade

AFIP


Undifferentiated endometrial sarcoma

• Macro:

‐ one or more tan‐yellow to grey fleshy i t itintracavitary

polypoid masses with hemorrhage or necrosis

Crum CP, Lee KR. Diagnostic gynecologicand obstetric pathology. 2006


Undifferentiated endometrial sarcoma

• Micro: ‐marked cellular atypia and numerous mitosis without evidence of differentiation towards endometrial stroma

• (diffuse and destructive infiltrative pattern)


Endometrial stromal tumors

• Smooth muscle tumor

• Mixed endometrial stromal‐smooth

muscle tumors

Differential diagnosis:

usc e tu o s• Uterine tumor resembling ovarian sex cord stromal tumor(UTROSCT)

• Endometrial polyp with atypical stroma

Rare heterologous tumour

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Mixed epithelial and mesenchymal tumors

• Adenomyoma ‐ benign

• ‐ Atypical polypoid variant

• Adenofibroma benign• Adenofibroma ‐ benign

• Carcinofibroma – very uncommon

• Adenosarcoma• Carcinosarcoma


• Adenomyoma‐ endocervical type..arising in cervix, polyp… benign endocervical glands and smooth muscle‐ endometrioid type.. polyp/ submucosal mass….benign endometrial glands and smooth muscle

Mixed epithelial and mesenchymal tumors

• Atypical polypoid adenomyoma‐ complex proliferation of glands with variable atypia admixed with cellular smooth muscle

• Adenofibroma ‐ benign epithelial and mesenchyal components‐much less frequent .. may be associated with tamoxifen therapy


AdenomyomaDEPARTMENT OF PATHOLOGYFACULTY OF MEDICINE SIRIRAJ HOSPITAL MAHIDOL UNIVERSITY

desmin

Atypical polypoid adenomyoma


Adenosarcoma

• Low grade mullerian adenosarcoma… admixture of a benign( or sometimes atypical) epithelial component with a low grade malignant stromal component ..8% of uterine sarcomasarcoma

• Postmenopausal ; associated risk.. Hyperestrinism (tamoxifen), prior radiation therapy

• Macro: endometrial lesion, cervix(9%), myometrium(4%)

Adenosarcoma

Polypoid, papillary intraluminalsoft to firm, spongy from cysts and cleftsreminescent of phyllodes tumor

≥4 mf/10 HPFs(≥2 mf/10 HPFs with marked cellularity /significant atypia)

Periglandular collaring..

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Adenosarcoma

• Sarcomatous overgrowth.. pure sarcoma at least 25% of the tumor volume(1 low power field /slide)…more invasive/ recurrence/ hematogenous metastases and death from tumor in 70% 40% and 60% oftumor in 70%, 40% and 60% of patients, respectively. (Am J Surg Pathol 13:28‐38, 1989)

• IPX: (+)vimentin, WT1, CD10, ER, PR

variable(+) CK, muscle actin, AR

Carcinosarcoma

• Malignant elements of epithelium and stroma regardless of whether malignant heterologous elements are presentor not.

Silverberg SG, Major FJ, Blessing JA, et al.:

Carcinosarcoma (malignant mixed mesodermal tumor) of the uterus. A Gynecologic Oncology Group pathologic study of 203 cases. Int J Gynecol Pathol 9 (1): 1-19, 1990.


Histogenesis:(1) The collision theory ‐ two independent neoplasms.

(2) The combination theory – both components are derived from a single stem cell that undergoes divergent differentiation early in the evolution of the tumour.

Carcinosarcoma

(3) The conversion theory ‐ the sarcomatous element derived from the carcinoma during the evolution of the tumour.

‘Metaplastic carcinoma’

Metastasis:‐ 3 patterns ‐ CA, Carcinosarcoma, Sarcoma

DEPARTMENT OF PATHOLOGYFACULTY OF MEDICINE SIRIRAJ HOSPITAL MAHIDOL UNIVERSITYCarcinosarcoma

STROMA

• Homologous type• Heterologous type

• mitotic activity of the stroma

• grade of the stromal components

• types of stromal heterologous elements

No relationship to metastases


Factors determining prognosis of uterine sarcoma

• Extent of disease at the time of diagnosis (2)

• For leiomyosarcomas, some consider tumor size to be the most important prognostic factor; greater than 5.0

i i i di h i (2)centimeters in maximum diameter have a poor prognosis.(2)

However, in a Gynecologic Oncology Group study, the mitotic index was the only factor significantly related to progression‐free interval.(3)

• Leiomyosarcomas matched for other known prognostic factors may be more aggressive than their carcinosarcomacounterparts.(4)


• For carcinosarcomas,

Predictors of metastasis

• isthmic or cervical location

Factors determining prognosis of uterine sarcoma (contd)

• LVSI

• serous and clear cell histology, and grade 2 or 3 carcinoma

Progression‐free interval

• adnexal spread, lymph node metastases, tumor size,

peritoneal cytologic findings, and depth of myometrial

invasion correlate 2)

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Perivascular epithelioid cell tumor

(PEComa)• Composed predominantly or exclusively of HMB‐45 positive perivascular

epithelioid cells with eosinophilic granular cytoplasm

• Age 40‐75 yrs( mean 54)/….. AUB/ …uncertain malignant potential• Macro: mass in uterine corpus

• Micro:1) tongue‐like growth pattern of low grade ESS, abundant eosinophilic granular/clear cytoplasm( diffuse HMB‐45 and variable muscle marker expressions)

• 2) lesser tongue‐like growth pattern of epithelioid cells with less prominent clear cytoplasm and a smaller number HMB‐45 (+)cells but more extensive muscle marker differentiation

• Genetic susceptibility:

‐ pelvic nodes involved by lymphangioleiomyomatosis

‐ one fourth had tuberous sclerosis


Adenomatoid tumor

• Benign tumor of mesothelium forming gland like structures• Site: uterine serosa, myometrium• Macro: softer, less well defined than leiomyoma • Micro: multiple small, often slit‐like interconnecting spaces

within the myometrium lined by cuboidal or attenuatedwithin the myometrium lined by cuboidal or attenuated cells….infiltrative appearance..

‐may be confused with lymphangioma ‐ little nuclear atypia, signet ring like‐ no stromal desmoplastic response

• IPX... Positive keratin and mesothelial markers


References1. Crum CP, Lee KR. Diagnostic gynecologic and obstetric pathology.

20062. Major FJ, Blessing JA, Silverberg SG, et al. Prognostic factors in early

stage uterine sarcoma. A Gynecologic Oncology Group Study. Cancer 71( 4Suppl);1993:1702-9

3. Evans HL, Chawla SP, Simpson C, et al. Smooth muscle neoplasm of the uterus other than ordinary leiomyoma. A study of 46 cases, with emphasis on diagnostic criteria and prognostic factors Cancer 62(10);emphasis on diagnostic criteria and prognostic factors. Cancer 62(10); 1988:2239-47

4. Oláh KS, Dunn JA, Gee H. Leiomyosarcoma have a poorer prognosis than mixed mesodermal tumor when adjusting for known prognostic factors: the result of a retrospective study of 423 cases of uterine sarcoma. Br J Obstet Gynecol 99(7);1992:590-4

5. Nucci MR, Oliva E. Gynecologic pathology. China: Churchill Livingstone; 2009

6. Tavassoli FA, Devilee P. WHO classification of tumors. Tumors of the breast and female genital organs. 2003

7. Robboy J, Mutter GL, Prat J,Bently RC,Russel P, Anderson MC. Robboy’s pathology of the female reproductive tract. 2nd ed. 2009


Any questions?

Thank You for Your Attention

non-epithelial tumors uterine tumors - iop pathology/… · · 2015-04-06muscle tumor s08-17284of...

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