22/02/53

DEPARTMENT OF PATHOLOGY FACULTY OF MEDICINE SIRIRAJ HOSPITAL MAHIDOL UNIVERSITY

DEPARTMENT OF PATHOLOGY FACULTY OF MEDICINE SIRIRAJ HOSPITAL MAHIDOL UNIVERSITY

Scope

Non-epithelial Uterine Tumors
Tuenjai Chuangsuwanich, M.D. Department of Pathology, Faculty of Medicine Siriraj Hospital, Mahidol University.
20-02-10

• 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

• •

DEPARTMENT OF PATHOLOGY FACULTY OF MEDICINE SIRIRAJ HOSPITAL MAHIDOL UNIVERSITY

DEPARTMENT OF PATHOLOGY FACULTY OF MEDICINE SIRIRAJ HOSPITAL MAHIDOL UNIVERSITY

Smooth muscle tumors
• Leiomyoma and leiomyoma variants • Leiomyosarcoma • Borderline smooth muscle tumor/ Smooth  muscle tumor of uncertain malignant  potential (STUMP)

Leiomyoma

S08-17284

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 cigarshaped nuclei. Mitosis is rare. Necrosis is absent.
Malee M.D.

DEPARTMENT OF PATHOLOGY FACULTY OF MEDICINE SIRIRAJ HOSPITAL MAHIDOL UNIVERSITY

Leiomyoma, histological variants
• Leiomyoma ‐ with degenerative changes ‐ with hydropic change ‐ with hormonal induced changes (hemorrhagic/apoplectic)  • 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 Myxoid id change h

Hydropic and cystic change

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

1

Oliva E. China: Churchill Livingstone. 2009 DEPARTMENT OF PATHOLOGY FACULTY OF MEDICINE SIRIRAJ HOSPITAL MAHIDOL UNIVERSITY Leiomyoma with bizarre nuclei (Atypical leiomyoma) Lipoleiomyoma 1A4 DEPARTMENT OF PATHOLOGY FACULTY OF MEDICINE SIRIRAJ HOSPITAL MAHIDOL UNIVERSITY Leiomyoma. Oliva E. Gynecologic pathology. Prat J. 2009 Nucci MR. 2nd ed. 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. 2009 2 .22/02/53 Cellular  and highly cellular leiomyoma Epithelioid leiomyoma Nucci MR. Gynecologic pathology.Russel P. Mutter GL.Bently RC. China: Churchill Livingstone. Robboy’s pathology of the female reproductive tract. Anderson MC.

Oliva E. usually not associated with leiomyoma . China: Churchill Livingstone. 2009 DEPARTMENT OF PATHOLOGY FACULTY OF MEDICINE SIRIRAJ HOSPITAL MAHIDOL UNIVERSITY DEPARTMENT OF PATHOLOGY FACULTY OF MEDICINE SIRIRAJ HOSPITAL MAHIDOL UNIVERSITY Intravenous leiomyomatosis Leiomyosarcoma ‘Malignant smooth muscle tumor’ • 1% of all uterine malignancies • 0. China: Churchill Livingstone. DEPARTMENT OF PATHOLOGY FACULTY OF MEDICINE SIRIRAJ HOSPITAL MAHIDOL UNIVERSITY DEPARTMENT OF PATHOLOGY FACULTY OF MEDICINE SIRIRAJ HOSPITAL MAHIDOL UNIVERSITY Leiomyosarcoma Micro: Leiomyosarcoma • Atypia • Mitotic figure……Atypical  mitosis • Necrosis:  geographic coagulation necrosis Nucci MR. Oliva E. exam.64 cases per 100. fleshy. 2009 Nucci MR.intramural . Oliva E. poorly defined margins Hemorrhage and necrosis • • • • Cellularity Infiltrative pattern Vascular invasion Metastasis 3 . Gynecologic pathology. China: Churchill Livingstone.22/02/53 Dissecting leiomyoma including cotyledonoid leiomyoma Diffuse leiomyomatosis peritonealis Nucci MR. Gynecologic pathology.000 women • present later in life around or after menopause    • unsuspected or presumed to be leiomyoma before  patho. 2009 Macro: . Gynecologic pathology.average 8 cm .

Robboy’s pathology of the female reproductive tract.Apoplectic leiomyoma . 2009 DEPARTMENT OF PATHOLOGY FACULTY OF MEDICINE SIRIRAJ HOSPITAL MAHIDOL UNIVERSITY DEPARTMENT OF PATHOLOGY FACULTY OF MEDICINE SIRIRAJ HOSPITAL MAHIDOL UNIVERSITY Leiomyosarcoma • Types of leiomyosarcoma ‐ Conventional. minimal atypia low mitotic count ( mitotic count ≥ 2/10HPF. myxoid  LMS) Epithelioid leiomyosarcoma Differential diagnoses: ‐ myxoid LM ‐ hydropic LM ‐ myxoid EST ‐ intravenous leiomyomatosis • . spindle.et al. NOS ‐ Epithelioid E ith li id ‐ Myxoid Conventional LMS DDx .Mitotically active leiomyoma .  maybe well defined margin grossly hypocellular.Leiomyoma with bizarre nuclei .Myxoid leiomyoma DEPARTMENT OF PATHOLOGY FACULTY OF MEDICINE SIRIRAJ HOSPITAL MAHIDOL UNIVERSITY DEPARTMENT OF PATHOLOGY FACULTY OF MEDICINE SIRIRAJ HOSPITAL MAHIDOL UNIVERSITY Myxoid leiomyosarcoma Soft grey gelatinous surface.. 2nd ed..22/02/53 DEPARTMENT OF PATHOLOGY FACULTY OF MEDICINE SIRIRAJ HOSPITAL MAHIDOL UNIVERSITY Leiomyosarcoma DEPARTMENT OF PATHOLOGY FACULTY OF MEDICINE SIRIRAJ HOSPITAL MAHIDOL UNIVERSITY Necrosis Frequent mitosis hypercellularity Atypia Complex/ geographic Sharp outline Atypical nuclei in necrotic area Spared vessels Tumor/ geographic necrosis Necrosis Infiltrativeness Robboy J. Round to polygonal cells in > 50% of tumor ‐ Softer may lack whorled cut surface ‐ Eosinophilic/clear cytoplasm ‐ Round nuclei 4 .Highly cellular leiomyoma .

UTROSCT .  ‐ ‐ LM with bizarre  nuclei ‐ ‐ ≤10 ≤15 Mitotically    active LM ‐ DEPARTMENT OF PATHOLOGY FACULTY OF MEDICINE SIRIRAJ HOSPITAL MAHIDOL UNIVERSITY Smooth muscle tumor DEPARTMENT OF PATHOLOGY FACULTY OF MEDICINE SIRIRAJ HOSPITAL MAHIDOL UNIVERSITY Smooth muscle markers Immunohistochemistry • Smooth muscle markers:(variable in LMS) ‐ smooth muscle actin.Poorly differentiated carcinoma .Endometrial stromal sarcoma .Malignant melanoma/ alveolar soft part sarc/ rhabdoid tumor AE1/AE3 -Any degree of cytologic artypia and ≥5 mf /10HPFs without necrosis . PR in nearly 100% ‐ AR  in  30% ‐ WT‐1 p53 minimal to absent in benign MiB-1( Ki-67) Smooth muscle actin. smooth muscle    myosin. moderate to severe +  or  ‐ None Diffuse/multifocal.PSTT /ETT . moderate to severe ‐ Questionable >10 Any rate >15    Approaching      but<10 STUMP ‐ Type of necrosis…uncertain ‐ Borderline number of mitotic figures These interpretation will result in different criteria of justifying  malignancy. Diagnostic gynecologic and obstetric pathology. EMA (more often epithelioid variant) ‐ CD10 variable bl  positivity ‐ ER.≥5 mf /10HPFs without necrosis with necrosis with any degree of cytologic atypia 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  criteria ‐ Subtype of smooth muscle differentiation in doubt…standard/epithelioid/myxoid DEPARTMENT OF PATHOLOGY FACULTY OF MEDICINE SIRIRAJ HOSPITAL MAHIDOL UNIVERSITY DEPARTMENT OF PATHOLOGY FACULTY OF MEDICINE SIRIRAJ HOSPITAL MAHIDOL UNIVERSITY Practical classification of  smooth muscle tumors Diagnosis Leiomyosar   ‐coma Necrosis + mf/10hpf Any rate Atypia +  or  ‐ Diffuse/ multifocal.22/02/53 DEPARTMENT OF PATHOLOGY FACULTY OF MEDICINE SIRIRAJ HOSPITAL MAHIDOL UNIVERSITY DEPARTMENT OF PATHOLOGY FACULTY OF MEDICINE SIRIRAJ HOSPITAL MAHIDOL UNIVERSITY Epithelioid leiomyosarcoma Epithelioid LMS DDx .PEComa . keratin. desmin. Lee KR. 2006 h-caldesmon Smooth muscle myosin heavy chain 5 . moderate to severe Diffuse/ multifocal. h‐caldesmon ‐ oxytocin.1A4 Desmin Smooth muscle markers Crum CP.

17)(p15.  polypoid l id ‐ Compose of cells morphologically resemble  nonneoplastic proliferative  phase endometrial  stroma  and prominent spiral arteriole‐like vascular component. Lee KR.  ‐ mf 1‐5/10HPFs.diffuse CD10(+).7 cm. subserosal.pelvic pain • Macro: Well delineated.22/02/53 DEPARTMENT OF PATHOLOGY FACULTY OF MEDICINE SIRIRAJ HOSPITAL MAHIDOL UNIVERSITY Endometrial stromal tumors(EST) DEPARTMENT OF PATHOLOGY FACULTY OF MEDICINE SIRIRAJ HOSPITAL MAHIDOL UNIVERSITY Endometrial stromal nodule(ESN) • Very rare. an  admixture of endometrial  stromal and smooth muscle  elements……. low grade ‐ undifferentiated endometrial sarcoma DEPARTMENT OF PATHOLOGY FACULTY OF MEDICINE SIRIRAJ HOSPITAL MAHIDOL UNIVERSITY Endometrial stromal nodule DEPARTMENT OF PATHOLOGY FACULTY OF MEDICINE SIRIRAJ HOSPITAL MAHIDOL UNIVERSITY Crum CP. . Focal irregularity not exceed  3 mm.diffusely (-)desmin. focal 1A4.a minimum of  30% of f the h  minor i   component • Should be evaluated  and  reported in the same way as  EST Mixed endometrial stromal and smooth muscle tumor CD10 Desmin 1A4 6 . 2006 .focal irregularities not exceeding 3 mm .   ‐ hypercellular/hypocellular/myxoid/epithelioid. expansile  margin. 47. . Cytogenetic abnormalities in low grade ESS  chromosome rearrangements  involving chromosomes  p  balanced  6. and smooth muscle myosin heavy chain(+) in the tumor and th peripheral area.. no  vascular invasion WHO 2003 Classification: ‐ endometrial stromal nodule ‐ endometrial stromal sarcoma. No angiolymphatic invasion DEPARTMENT OF PATHOLOGY FACULTY OF MEDICINE SIRIRAJ HOSPITAL MAHIDOL UNIVERSITY DEPARTMENT OF PATHOLOGY FACULTY OF MEDICINE SIRIRAJ HOSPITAL MAHIDOL UNIVERSITY Mixed endometrial stromal and smooth muscle  tumor • Stromomyoma. (Mitotic figures=1-2/10 HPFs.AUB . median age.7 and 17/  most common reciprocal translocation:‐ t(7.q21)  … ( chimeric JAZF1‐JJAZ1 mRNA transcripts) • Micro: Endometrial stromal cells and prominent spiral arteriole‐ like vascular component. intramyometrial.  soft tan yellow cut surface. Diagnostic gynecologic and obstetric pathology. mean diameter. smooth muscle metaplasia at the periphery.

Lee KR. low grade DEPARTMENT OF PATHOLOGY FACULTY OF MEDICINE SIRIRAJ HOSPITAL MAHIDOL UNIVERSITY DEPARTMENT OF PATHOLOGY FACULTY OF MEDICINE SIRIRAJ HOSPITAL MAHIDOL UNIVERSITY DEPARTMENT OF PATHOLOGY FACULTY OF MEDICINE SIRIRAJ HOSPITAL MAHIDOL UNIVERSITY Endometrial stromal sarcoma.22/02/53 DEPARTMENT OF PATHOLOGY FACULTY OF MEDICINE SIRIRAJ HOSPITAL MAHIDOL UNIVERSITY 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)  Endometrial stromal sarcoma. 2006 DEPARTMENT OF PATHOLOGY FACULTY OF MEDICINE SIRIRAJ HOSPITAL MAHIDOL UNIVERSITY DEPARTMENT OF PATHOLOGY FACULTY OF MEDICINE SIRIRAJ HOSPITAL MAHIDOL UNIVERSITY Endometrial stromal tumors Undifferentiated endometrial sarcoma Differential diagnosis: • Smooth muscle tumor • Mixed endometrial stromal‐smooth   muscle usc e tumors tu o s • Uterine tumor resembling ovarian  sex cord stromal  tumor(UTROSCT) • Endometrial polyp with atypical stroma • • Micro: ‐ marked cellular atypia and numerous mitosis without   evidence of differentiation towards endometrial  stroma (diffuse and destructive  infiltrative pattern) „ Rare heterologous tumour 7 . Diagnostic gynecologic and obstetric pathology. low grade Undifferentiated endometrial sarcoma • Macro: ‐ one or more tan‐ yellow to grey fleshy  i t intracavitary it     polypoid masses with  hemorrhage  or  necrosis AFIP Crum CP.

. spongy from cysts and clefts reminescent of phyllodes tumor • Macro: endometrial lesion.22/02/53 DEPARTMENT OF PATHOLOGY FACULTY OF MEDICINE SIRIRAJ HOSPITAL MAHIDOL UNIVERSITY DEPARTMENT OF PATHOLOGY FACULTY OF MEDICINE SIRIRAJ HOSPITAL MAHIDOL UNIVERSITY Mixed epithelial and mesenchymal tumors • • • • • • Adenomyoma  ‐ benign ‐ Atypical polypoid variant Adenofibroma    ‐ benign Carcinofibroma – very uncommon Adenosarcoma Carcinosarcoma Mixed epithelial and mesenchymal tumors • Adenomyoma ‐ endocervical type. polyp… benign      endocervical glands and smooth muscle ‐ endometrioid type. polyp/ submucosal mass…. prior radiation therapy Polypoid.8% of uterine  sarcoma • Postmenopausal . Hyperestrinism  (tamoxifen).benign      endometrial glands and smooth muscle • Atypical polypoid adenomyoma ‐ complex proliferation of glands with variable atypia    admixed with cellular smooth muscle • Adenofibroma     ‐ benign epithelial and mesenchyal components ‐ much less frequent .. papillary intraluminal soft to firm. associated risk. cervix(9%). 8 ....arising in cervix. may be associated with tamoxifen therapy DEPARTMENT OF PATHOLOGY FACULTY OF MEDICINE SIRIRAJ HOSPITAL MAHIDOL UNIVERSITY DEPARTMENT OF PATHOLOGY FACULTY OF MEDICINE SIRIRAJ HOSPITAL MAHIDOL UNIVERSITY Adenomyoma Atypical polypoid adenomyoma desmin DEPARTMENT OF PATHOLOGY FACULTY OF MEDICINE SIRIRAJ HOSPITAL MAHIDOL UNIVERSITY Adenosarcoma Adenosarcoma • Low grade mullerian adenosarcoma… admixture of a  benign( or sometimes atypical) epithelial component with a low  grade malignant stromal component . myometrium(4%) ≥4 mf/10 HPFs (≥2 mf/10 HPFs with marked cellularity / significant atypia) Periglandular collaring..

 WT1.:  Carcinosarcoma  (malignant mixed  mesodermal tumor) of the uterus. (2) The combination theory – both components are derived from a single stem  cell that undergoes divergent differentiation early in the evolution of the  tumour.  Sarcoma DEPARTMENT OF PATHOLOGY FACULTY OF MEDICINE SIRIRAJ HOSPITAL MAHIDOL UNIVERSITY DEPARTMENT OF PATHOLOGY FACULTY OF MEDICINE SIRIRAJ HOSPITAL MAHIDOL UNIVERSITY Factors  determining prognosis of uterine  sarcoma • Extent of disease at the time of diagnosis (2) • For leiomyosarcomas. Silverberg SG. STROMA • Homologous type • Heterologous type • mitotic activity of the stroma • grade of the stromal components • types of stromal heterologous elements No relationship to metastases (3) The conversion theory ‐ the sarcomatous element derived from the  carcinoma during the evolution of the tumour.0  centimeters i  in i  maximum i  diameter di  have h  a poor prognosis. muscle actin.  Predictors of metastasis  • isthmic or cervical location  • LVSI   • serous and clear cell histology. Carcinosarcoma. 1989) Carcinosarcoma • Malignant elements  of epithelium and  stroma  regardless of  whether malignant  heterologous  elements are present or not.  peritoneal cytologic findings.. Major FJ. i (2)  However. tumor size. 70%  40% and 60% of  patients. and depth  of myometrial  invasion correlate 2) 9 . CD10.  PR variable(+) CK. • IPX: (+)vimentin. respectively.(3) • Leiomyosarcomas matched for other known prognostic  factors may be more aggressive than their carcinosarcoma counterparts. (Am J Surg  Pathol 13:28‐38.  ‘Metaplastic carcinoma’ Metastasis: ‐ 3 patterns  ‐ CA. 1990.22/02/53 DEPARTMENT OF PATHOLOGY FACULTY OF MEDICINE SIRIRAJ HOSPITAL MAHIDOL UNIVERSITY Adenosarcoma • Sarcomatous overgrowth. Blessing JA.(4) Factors  determining prognosis of uterine  sarcoma (contd) • For carcinosarcomas. ER.  AR DEPARTMENT OF PATHOLOGY FACULTY OF MEDICINE SIRIRAJ HOSPITAL MAHIDOL UNIVERSITY Carcinosarcoma DEPARTMENT OF PATHOLOGY FACULTY OF MEDICINE SIRIRAJ HOSPITAL MAHIDOL UNIVERSITY Carcinosarcoma Histogenesis: (1) The collision theory ‐ two independent neoplasms. and grade 2 or 3 carcinoma Progression‐free interval • adnexal spread. et al. some consider tumor size to be the  most important prognostic factor. greater than 5. lymph node metastases. A  Gynecologic Oncology  Group pathologic  study of 203 cases. Int J Gynecol Pathol 9 (1): 1-19. the mitotic  index was the only factor significantly related to progression‐ free interval. in a Gynecologic Oncology Group study. 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%.

 AUB/ …uncertain malignant potential • Macro: mass in uterine corpus • Micro:1) tongue‐like growth pattern of low grade ESS. Mutter GL. Br J Obstet Gynecol 99(7). A study of 46 cases. Silverberg SG. 2009 Any questions? 4.22/02/53 DEPARTMENT OF PATHOLOGY FACULTY OF MEDICINE SIRIRAJ HOSPITAL MAHIDOL UNIVERSITY DEPARTMENT OF PATHOLOGY FACULTY OF MEDICINE SIRIRAJ HOSPITAL MAHIDOL UNIVERSITY 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)/…. Positive keratin and mesothelial markers DEPARTMENT OF PATHOLOGY FACULTY OF MEDICINE SIRIRAJ HOSPITAL MAHIDOL UNIVERSITY DEPARTMENT OF PATHOLOGY FACULTY OF MEDICINE SIRIRAJ HOSPITAL MAHIDOL UNIVERSITY References 1. Cancer 71( 4Suppl). Oliva E. A Gynecologic Oncology Group Study.1993:1702-9 Evans HL. Gynecologic pathology. 2009 Tavassoli FA. factors Cancer 62(10).. 2003 Robboy J. 6. et al.infiltrative appearance. Devilee P. with emphasis on diagnostic criteria and prognostic factors. WHO classification of tumors.1992:590-4 Nucci MR.. signet ring like ‐ no stromal desmoplastic response • IPX. Tumors of the breast and female genital organs. Simpson C. Smooth muscle neoplasm of the uterus other than ordinary leiomyoma.  ‐ may be confused with lymphangioma  ‐ little nuclear atypia. 2006 Major FJ. 5. Prat J. 3. 2.Bently RC. 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. Blessing JA. Thank You for Your Attention 10 . less well defined than leiomyoma  Micro: multiple small. 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. Dunn JA. et al.. China: Churchill Livingstone. Prognostic factors in early stage uterine sarcoma. Anderson MC. Gee H. Crum CP. 2nd ed. 7. Lee KR. Robboy’s pathology of the female reproductive tract.Russel P.. 1988:2239-47 Oláh KS. often slit‐like interconnecting  spaces  within the myometrium lined by cuboidal or attenuated  cells…. Chawla SP. Diagnostic gynecologic and obstetric pathology. myometrium Macro: softer.

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