5/25/2013 Current Approach to Diagnostic Pathology Uterine Cancer: - - PowerPoint PPT Presentation

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5/25/2013 Current Approach to Diagnostic Pathology Uterine Cancer: - - PowerPoint PPT Presentation

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5/25/2013 Current Approach to Diagnostic Pathology Uterine Cancer: 1. Understanding how pathologic evaluation allows a surgeon to make the best decisions about current treatment options. Practical Approach to Histologic Subtyping 2.

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Uterine Cancer: Practical Approach to Histologic Subtyping

Joseph Rabban MD MPH Associate Professor Pathology Department “Current” Approach to Diagnostic Pathology

  • 1. Understanding how pathologic evaluation allows a surgeon to make

the best decisions about current treatment options.

  • 2. Understanding current criteria to classify tumors and navigate

problematic cases. Treatment Decisions for Uterine Carcinoma

  • 1. Surgery versus Trial of Hormonal Therapy
  • 2. Extent of Surgery
  • 3. Type of Adjuvant Therapy
  • 4. Candidacy for Lynch syndrome evaluation

UCSF Gyn Onc Division, 2013

High Risk Tumor Behavior Treatment Decisions for Uterine Carcinoma Advanced stage at presentation Chemoresistance Local recurrence Distant metastasis Death

UCSF Gyn Onc Division, 2013

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High Risk Tumor Behavior High Risk Tumor Criteria Treatment Decisions for Uterine Carcinoma Advanced stage at presentation Chemoresistance Recurrence locally Distant metastasis Death Any grade 3 sub-type (serous, clear cell, carcinosarcoma, endometrioid)

Or

Grade 1, 2 endometrioid type with any: Lymphovascular invasion Myometrial/cervical/adnexal involvement Lymph node involvement

UCSF Gyn Onc Division, 2013

Decision 1. Surgery versus Trial of Hormonal Therapy Surgery is the default unless: Treatment Decisions for Uterine Carcinoma Trial of Hormone Therapy Grade 1 Endometrioid adenocarcinoma AND Fertility preservation Poor surgical candidate

UCSF Gyn Onc Division, 2013

Decision 2. Extent of Surgery Hysterectomy g1 Endometrioid, no Myoinvasion/LVI Plus pelvic lymph nodes g1 Endometroid, +Myoinvasion Plus para-aortic lymph nodes: g1,2 Endometrioid, +Myo / LVI / CX invasion g3 Endometrioid Clear cell carcinoma Plus omentectomy: Serous carcinoma Carcinosarcoma Treatment Decisions for Uterine Carcinoma Biopsy / Frozen Section

UCSF Gyn Onc Division, 2013

Decision 3. Type of Adjuvant Treatment Treatment Decisions for Uterine Carcinoma None grade 1, stage 1 endometrioid, no LVI Chemotherapy grade 2 or 3 endometrioid / age / LVI / MM invasion considered serous, clear cell, carcinosarcoma Radiation clear cell, serous, carcinosarcoma considered higher stage endometrioid Ifosfamide carcinosarcoma with rhabomyosarcoma elements considered Etoposide neuroendocrine carcinoma considered

UCSF Gyn Onc Division, 2013

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Decision 4. Candidate for Lynch syndrome screening ? Treatment Decisions for Uterine Carcinoma Any one criteria: Age < 50 Bethesda Guidelines criteria Tumor Morphology Tumor infiltrating lymphocytes Peritumoral lymphocytes Undifferentiated histology Lower uterine segment origin Concurrent ovarian cancer

UCSF Gyn Onc Division, 2013

4 Pathology Variables Drive these Clinical Decisions Treatment Decisions for Endometrial Carcinoma Sub-typing Grading Staging Lynch syndrome tumor morphology and testing WHO Classification of Uterine Carcinoma

  • Endometrioid adenocarcinoma
  • Serous carcinoma
  • Clear cell carcinoma
  • Transitional cell carcinoma
  • Mucinous carcinoma
  • Small cell carcinoma
  • Squamous cell carcinoma
  • Undifferentiated carcinoma
  • Carcinosarcoma
  • Mixed type (each type must be > 10% overall tumor)
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The Cancer Genome Atlas Classification of Uterine Cancer WHO Classification of Uterine Carcinoma

  • Endometrioid adenocarcinoma
  • Serous carcinoma
  • Clear cell carcinoma
  • Transitional cell carcinoma
  • Mucinous carcinoma
  • Small cell carcinoma
  • Squamous cell carcinoma
  • Undifferentiated carcinoma
  • Carcinosarcoma
  • Mixed type (each type must be > 10% overall tumor)

Outline of Talk Practical issues: Problematic variations: A pattern-based approach Immunostain pearls and pitfalls Newer non-WHO definition of undifferentiated uterine carcinoma Practical Approach to Classifying Uterine Carcinoma Evaluate in order : Clinical context: Menopausal status / age Low magnification: Architecture High magnification: Cytology Adjacent tissue: Precursor lesion If needed: Immunohistochemistry

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Practical Approach to Classifying Uterine Carcinoma

Pre- Precursor IHC menopause lesion Endometrioid,g1,2 yes Atypical hyperplasia ER, PTEN loss Endometrioid,g3 uncommon Atypical hyperplasia ER, p16, p53 Serous uncommon Serous EIC p53, p16 Clear cell uncommon ? HNF Undifferentiated uncommon ? EMA/Keratin loss

Proteus: the “shape shifter” Problematic Patterns of Uterine Cancer

Pure glandular Papillary Solid, with high grade nuclei Spindled Clear cell-rich Mucin-rich Necrosis, desmoplasia in a biopsy with low grade architecture Pure glandular

Grade 1 endometrioid carcinoma Pseudo-glandular serous carcinoma

Papillary

Papillary endometrioid carcinoma Serous carcinoma Villoglandular endocervical adenocarcinoma

Solid, with high grade nuclei

Solid serous carcinoma Grade 3 endometrioid carcinoma Undifferentiated carcinoma Neuroendocrine carcinoma

Spindled

Endometrioid carcinoma with spindle cells Endometrioid carcinoma with corded and hyalinized pattern Endometrioid carcinoma arising in APA Carcinosarcoma

Clear cell-rich

Endometrioid carcinoma with clear cells Serous carcinoma with clear cells Clear cell carcinoma

Mucin-rich

Endometrioid carcinoma with mucinous cells Endocervical carcinoma

Necrosis, desmoplasia in a biopsy with low grade architecture

Myoinvasive g 1 endometrioid carcinoma or serous carcinoma Under-sampled dedifferentiated carcinoma / g3 endometrioid

Problematic Patterns of Uterine Cancer

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Problematic Patterns of Uterine Cancer

Pure glandular Papillary Solid, with high grade nuclei Spindled Clear cell-rich Hobnail , papillary, clear cell Mucinous Necrosis, desmoplasia in a biopsy with low grade architecture

Pure Glandular Pattern Uterine Cancer Complex Atypical Hyperplasia Grade 1 Endometrioid Carcinoma Pseudoglandular Serous Carcinoma (grade 3) @ low magnification:

  • Simple gland shape
  • Columnar cells

Pseudoglandular Serous Carcinoma Pseudoglandular Serous Carcinoma

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Pseudoglandular Serous Carcinoma Pseudoglandular Serous Carcinoma Pseudoglandular Serous Carcinoma Pseudoglandular Serous Carcinoma in a polyp

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Grade 1 Pseudoglandular Endometrioid Serous Architectural Grade Low Low Nuclear Low High Grade Discordant architecture versus nuclear grade

  • Pleomorphic nuclei
  • Cherry-red macronucleoli
  • Smudge cells
  • Atypical mitoses

Pure Glandular Pattern Uterine Cancer Endometrioid carcinoma Serous carcinoma

(upper end of size) irregular, large, cherry-red

Nucleoli Pseudoglandular Serous Carcinoma: Atypical mitoses Pseudoglandular Serous Carcinoma: Smudged chromatin

Normal N/C ratio

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Atrophy “Early serous carcinoma” “Serous EIC” Serous Carcinoma

Look for Precursor Lesion Adenomyosis Myoinvasion by Pseudoglandular Serous cancer Architectural Grade Low Low Nuclear Low High Grade Discordant architecture versus nuclear grade

  • Pleomorphic nuclei
  • Cherry-red macronucleoli
  • Smudge cells
  • Atypical mitoses

Pure Glandular Pattern Uterine Cancer Pseudoglandular Serous Carcinoma “Gaping” glands Pseudoglandular Serous Carcinoma: Myoinvasion

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mimics adenomyosis Pseudoglandular Serous Carcinoma: Myoinvasion mimics adenomyosis Pseudoglandular Serous Carcinoma: Myoinvasion LVI in Serous Carcinoma may occur without myoinvasion Glandular Pattern of Endometrial Cancer Architectural Grade Low Low Nuclear Low High Grade p16, p53 Wild type Aberrant ER Diffuse, strong Variable Grade 1 Pseudoglandular Endometrioid Serous

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p53 IHC Interpretation in GYN Serous Carcinoma

Yemenelyanova 2011 Mod Pathol Strong/diffuse (>60% cells) 90 % Completely negative 88 % Weak/patchy (rare to 50%) 20 % Pattern of p53 IHC staining p53 gene mutation Pattern of p53 IHC staining Stain Interpretation Meaning Strong/diffuse (>60% cells) Aberrant p53 Favor serous carcinoma Completely negative Weak/patchy (rare to 50%) Wild type p53 (normal) Not serous carcinoma

p53 IHC Interpretation in GYN Serous Carcinoma

Wild type p53 Aberrant p53 Aberrant p53 Favor serous carcinoma Favor serous carcinoma Not serous carcinoma Check for internal control

p53 interpretation in GYN Serous Carcinoma

Diffuse / strong p16 Patchy p16

Favor serous carcinoma Not in favor of serous carcinoma

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Endometrioid Adenocarcinoma, grades 1 & 2

p53 p16 Wild type Patchy Pseudoglandular serous carcinoma p53 p16 Diffuse, strong Diffuse, strong

p53 p16

Pseudoglandular serous carcinoma Mixed pseudoglandular serous carcinoma plus grade 1 endometrioid cancer

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Mixed pseudoglandular serous carcinoma plus grade 1 endometrioid cancer p53 Mixed pseudoglandular serous carcinoma plus grade 1 endometrioid cancer p16 Mixed pseudoglandular serous carcinoma plus grade 1 endometrioid cancer Estrogen Receptor

PTEN Mutation

Common in endometrioid carcinoma Uncommon in non-endometrioid carcinoma

Matias-Guiu & Prat 2013 Histopathology

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Matias-Guiu & Prat 2013 Histopathology

PTEN Mutation PTEN Loss by IHC

Common in endometrioid carcinoma Uncommon in non-endometrioid carcinoma Normal endometrium Rare Hyperplasia ~30% Atypical hyperplasia ~75% Endometrioid cancer ~60-75% Non-endometrioid cancer ~25-35%

Djordjevic 2013 Mod Pathol Darvishian 2004 AJSP Mutter 2000 JNCI

Endometrioid cancer Serous carcinoma Clear cell carcinoma PTEN complete negative PTEN present PTEN present

PTEN IHC in uterine cancer subtypes Pseudoglandular serous carcinoma How to avoid under-recognition

  • Before diagnosing atypical hyperplasia or grade 1 endometrioid carcinoma
  • p53
  • p16
  • ER

Is cytology concordant ? Yes No Diagnosis Rule out is Serous Confirmed Carcinoma

Glandular Papillary Solid, with high grade nuclei Spindled Clear cell-rich Mucin-rich Necrosis, desmoplasia in a biopsy with low grade architecture

Problematic Patterns of Uterine Cancer

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Papillary Pattern of Uterine Cancer Serous Carcinoma Papillary variants of Endometrioid Adenocarcinoma (grade 1 or 2)

Villoglandular variant Small non-villous papillary variant

Villoglandular Endocervical Adenocarcinoma Papillary variant Papillary Endometrioid Serous Carcinoma Carcinoma Architectural Grade Low Low Nuclear Low High Grade Discordant architecture versus nuclear grade

  • Pleomorphic nuclei
  • Cherry-red macronucleoli
  • Smudge cells
  • Atypical mitoses

Papillary Pattern Uterine Cancer Papillary variant Papillary Endometrioid Serous Carcinoma Carcinoma Architectural Grade Low Low Nuclear Low High Grade p53, p16 wild type aberrant ER diffuse, strong variable Papillary Pattern Uterine Cancer Papillary Serous Carcinoma

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Papillary Serous Carcinoma p16: diffuse / strong p53: diffuse / strong Villoglandular endometrioid adenocarcinoma Villoglandular endometrioid adenocarcinoma Villoglandular endometrioid adenocarcinoma

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Villoglandular endometrioid adenocarcinoma Villoglandular endometrioid adenocarcinoma Villoglandular endometrioid adenocarcinoma Villoglandular endocervical adenocarcinoma in “EMB” Clues to raise concern:

  • Young age (35-45)
  • Clinical lesion in endocervix
  • Apical: “Floating” mitoses
  • Basal: Apoptotic debris
  • Negative ER, Vimentin, p53
  • Diffuse, strong p16
  • mCEA can be positive
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Villoglandular endocervical adenocarcinoma in “EMB” Villoglandular endocervical adenocarcinoma in “EMB” Floating mitoses in apical cytoplasm Villoglandular endocervical adenocarcinoma in “EMB” Apoptotic debris Endometrioid adenocarcinoma with small non-villous papillae Mimics Serous Carcinoma

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Endometrioid adenocarcinoma with small non-villous papillae Endometrioid adenocarcinoma with small non-villous papillae Endometrioid adenocarcinoma with sloughing papillary “buds” Mimics Serous Carcinoma

Glandular Papillary Solid, with high grade nuclei Spindled Clear cell-rich Mucin-rich Necrosis, desmoplasia in a biopsy with low grade architecture

Problematic Patterns of Uterine Cancer

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Solid Pattern Uterine Cancer with High Grade Nuclei

Serous carcinoma Grade 3 endometrioid adenocarcinoma Undifferentiated uterine carcinoma Neuroendocrine carcinoma Undersampled carcinosarcoma Consider non-epithelial malignancies: Leiomyosarcoma Rhabdomyosarcoma Lymphoma Melanoma

Solid Pattern Uterine Cancer Grade 3 Solid Endometrioid Serous Carcinoma Carcinoma Columnar/polarized cells Focal No Tubular, glandular Focal No Squamous differentiation Focal No Papillary, slit like spaces No Focal LVI with papillary buds No Yes Scattered bizarre nuclei No Yes Precursor lesion Hyperplasia EIC Aberrant p53/p16 Sometimes Yes PTEN Lost Present

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Grade 3 endometrioid adenocarcinoma Grade 3 endometrioid adenocarcinoma Grade 3 endometrioid adenocarcinoma Solid pattern serous carcinoma

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Atrophy Solid pattern serous carcinoma Atrophy Serous EIC Solid pattern serous carcinoma

Main tumor Junction between tumor and endometrium

p53 p53 Solid pattern serous carcinoma Consensus Diagnosis p53 Staining

Endometrioid p53 Normal Serous p53 Positive

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Solid Pattern Uterine Cancer with High Grade Nuclei

Serous carcinoma Grade 3 endometrioid adenocarcinoma Undifferentiated uterine carcinoma Neuroendocrine carcinoma Undersampled carcinosarcoma Consider non-epithelial malignancies: Leiomyosarcoma Rhabdomyosarcoma Lymphoma Melanoma

Undifferentiated Uterine Carcinoma Definition: Significance:

  • Tumor without any morphologic or immunostain differentiation
  • Two forms:
  • Pure undifferentiated uterine carcinoma (UUC)
  • Mixed UUC with low grade endometrioid carcinoma = Dedifferentiated (DDUC)
  • Highly aggressive / fatal
  • UUC worse than grade 3 endometrioid
  • DDUC worse than grade 2 endometrioid

Undifferentiated Uterine Carcinoma Architecture: Cytology:

  • Sheets, rarely cords. No glands/tubules/squamous features.
  • Non-cohesive cells
  • Geographic necrosis
  • Myxoid stroma (sometimes)
  • Monotonous polygonal cells
  • Moderate atypia
  • Nucleoli, mitoses
  • Rhabdoid cells (sometimes)

Undifferentiated Uterine Carcinoma Architecture: Cytology:

  • Sheets, rarely cords. No glands/tubules.
  • Non-cohesive cells
  • Necrosis
  • Myxoid stroma
  • Monotonous polygonal cells
  • Moderate atypia
  • Nucleoli, mitoses
  • Rhabdoid
  • Keratin, EMA……………..negative or focal (<10%)
  • Neuroendocrine…………..negative or focal (<10%)
  • p16……………………….. Positive
  • ER/PR…………………….conflicting data
  • p53………………………..not studied

Immunostains:

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Undifferentiated Uterine Carcinoma Undifferentiated Uterine Carcinoma Undifferentiated Uterine Carcinoma Undifferentiated Uterine Carcinoma: Non-cohesive tumor cells

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Undifferentiated Uterine Carcinoma : Moderate atypia Undifferentiated Uterine Carcinoma: Rhabdoid cells Keratin: Undifferentiated Uterine Carcinoma Dedifferentiated Uterine Carcinoma Undifferentiated Low grade

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Keratin: Dedifferentiated Uterine Carcinoma Undifferentiated Low grade Undifferentiated Uterine Carcinoma Behavior: Treatment:

  • 40% to 60% die
  • Median survival is 6 months
  • Most deaths are within 5 years
  • For dedifferentiated uterine carcinoma, prognosis is the same

even if only 20% is undifferentiated carcinoma

  • Same as for high grade cancer
  • Often MSI-high so testing for Lynch syndrome is advised

Undifferentiated Uterine Carcinoma Practical issues: A diagnosis of exclusion. Use formal diagnostic criteria, not WHO criteria. Do not report dedifferentiated carcinoma as grade 2 endometrioid carcinoma

  • Even a minor % of undifferentiated component is adverse

Consider screening for Lynch syndrome Undifferentiated Uterine Carcinoma vs Endometrioid Carcinoma UUC Grade 3 Endometrioid Tubules, glands No Usually focally Squamous differentiation No Focally Geographic necrosis Common Rare Non-cohesive cells Yes No Rhabdoid cells Yes No Keratin/EMA <10% cells Diffuse

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Undifferentiated Uterine Carcinoma vs Serous Carcinoma UUC Serous Carcinoma Papillary growth No Usually focally Slit like spaces No Focally Nuclei Monotonous Pleomorphic Geographic necrosis Common Rare Non-cohesive cells Yes No Rhabdoid cells Yes No Keratin/EMA <10% cells Diffuse

Geographic necrosis is not pathognomonic for undifferentiated carcinoma

Serous carcinoma Pleomorphism & cohesion Biopsy with solid pattern high grade malignancy Reasonable to report as “high grade adenocarcinoma” with a comment if: How specific does the sub-typing need to be ?

  • The tumor is confirmed by IHC to be epithelial.
  • The comment discusses differential diagnosis.

Glandular Papillary Solid, with high grade nuclei Spindled Clear cell-rich Hobnail , papillary, clear cell Mucinous Necrosis, desmoplasia in a biopsy with low grade architecture

Problematic Patterns of Uterine Cancer

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Uterine Cancers with Spindle Cells Carcinosarcoma Endometrioid carcinoma with spindle cells, grade 1 or 2

Spindled/sarcomatoid type Corded and hyalinized type Progestin-treated type Arising in atypical polypoid adenomyoma

Spindled types Endometrioid Carcinoma Carcinosarcoma Uterine Cancers with Spindle Cells Atypia Lower grade High grade Spindle cells blend Yes No with glandular cells Heterologous elements No Common Aberrant p16, p53 No Yes Carcinosarcoma: sharp demarcation of 2 components Carcinosarcoma

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Carcinosarcoma: p53 (same for p16) Carcinosarcoma with rhabdomyosarcomatous elements Carcinosarcoma with rhabdomyosarcomatous elements Desmin Myogenin Endometrioid carcinoma with spindle cells

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Endometrioid carcinoma with spindle cells Endometrioid carcinoma with spindle cells Endometrioid carcinoma with spindle cells Endometrioid carcinoma, corded and hyalinized type

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Endometrioid carcinoma, corded and hyalinized type Endometrioid carcinoma, corded and hyalinized type Endometrioid carcinoma, partial response to progestins Endometrioid carcinoma, partial response to progestins

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Endometrioid carcinoma arising in atypical polypoid adenomyoma

Glandular Papillary Solid, with high grade nuclei Spindled Clear cell-rich Mucin-rich Necrosis, desmoplasia in a biopsy with low grade architecture

Problematic Patterns of Uterine Cancer Clear cell-rich Endometrial Cancers Clear cell carcinoma Endometrioid carcinoma with clear cells / secretory change, any grade Serous carcinoma with clear cells Clear Cell-rich Uterine Cancer Endometrioid Carcinoma Clear Cell With Clear Cells Carcinoma Cell shape Columnar Polygonal Cell polarity Preserved Lost Tubulocystic plus Not common Yes papillary growth Hyaline globules No Yes Hyalinized stroma No Yes Hobnail growth No Yes Open tumor rings No Yes

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Clear cell carcinoma: polygonal cells, central nuclei Clear cell carcinoma: papillary & tubulocystic growth Clear Cell Carcinoma Clear Cell Carcinoma Hyalinized stroma Hyaline droplets

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Clear Cell Carcinoma Free floating open rings Endometrioid adenocarcinoma with clear cells Endometrioid adenocarcinoma with clear cells

Endometrioid adenocarcinoma with clear cells

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Serous carcinoma with clear cells

IHC of Uterine Clear Cell Carcinoma HNF-1 Positivity ER <10 % p53 variable p16 <50% HNF-1 >75%

HNF-1 Expression

Clear cell 94 - 98 % 73 - 100 % Endometrioid 0 - 40 %* 0 - 35 %* Serous 0 - 30 %* 0 - 60 %* Secretory phase Gestational phase positive Arias Stella reaction

Yamamoto 2007 Hum Pathol Fadare 2012 AIMM Kao 2012 Histopathol Delair 2011 AJSP Kobel 2009 AJSP Kato 2006 Mod Pathol Yamamoto 2007 Hum Pathol

*weak/patchy staining

OVARY UTERUS High grade solid cancer with clear cells

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IHC favors Serous Carcinoma with clear cells p53 p16 ER HNF Aberrant Aberrant Positive Negative

Lack of a distinct “separate” compartment is against a second tumor component Lack of a distinct “separate” compartment is against a second tumor component

ARID1A Mutation Common in Clear Cell Cancer Endometrioid Cancer

TCGA 2013 Nature Jones 2010 Science Wiegand 2010 NEJM

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ARID1A Mutation ARID1A Loss by IHC

TCGA 2013 Nature Jones 2010 Science Wiegand 2010 NEJM

Common in Clear Cell Cancer Endometrioid Cancer Endometrioid, grade 1 or 2 29 % Endometrioid, grade 3 39 % Clear cell carcinoma 26 % Serous carcinoma 18% Wiegand 2011 J Pathol Moderate level of disagreement

Glandular Papillary Solid, with high grade nuclei Spindled Clear cell-rich

  • Mucin-rich

Necrosis, desmoplasia in a biopsy with low grade architecture

Problematic Patterns of Uterine Cancer Mucin-rich Endometrial Cancers Endometrioid carcinoma with mucinous features Endocervical adenocarcinoma Endometrioid carcinoma with microglandular hyperplasia-like features

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Endometrioid adenocarcinoma with mucinous features Endometrioid adenocarcinoma with mucinous features

Endocervical MGH-like changes at surface/periphery of endometrial cancer Low grade, low stage endometrioid / mucinous adenocarcinoma Older women

Endometrial carcinoma with microglandular hyperplasia-like features Benign endocervical MGH

Endometrial carcinoma with microglandular hyperplasia-like features

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Endometrial carcinoma with microglandular hyperplasia-like features Glandular Papillary Solid, with high grade nuclei Spindled Clear cell-rich Mucin-rich Necrosis, desmoplasia in a biopsy with low grade architecture

Problematic Patterns of Uterine Cancer Necrosis or Desmoplasia in a Biopsy with Low Grade Tumor

Degenerative changes Myoinvasive grade 1 endometrioid tumor Myoinvasive pseudo-glandular serous carcinoma Under-sampled higher grade tumor

  • Grade 2 or 3 endometrioid carcinoma
  • Dedifferentiated uterine carcinoma
  • Carcinosarcoma

Necrosis + low grade adenocarcinoma

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Desmoplasia + low grade adenocarcinoma

Biopsy = Grade 1 Endometrioid cancer with necrosis Hysterectomy = Grade 3 Endometrioid cancer

Grade 1 Grade 3 Necrosis or Desmoplasia in a Biopsy with Low Grade Tumor

Degenerative changes Myoinvasive grade 1 endometrioid tumor Myoinvasive pseudo-glandular serous carcinoma Under-sampled higher grade tumor

  • Grade 2 or 3 endometrioid carcinoma
  • Dedifferentiated uterine carcinoma
  • Carcinosarcoma

Report as:

Adenocarcinoma with extensive necrosis; see comment. Adenocarcinoma with desmoplastic stroma; see comment. Discuss possibilities of higher grade or higher stage tumor.

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Outline of Talk Practical issues: Problematic variations: A pattern-based approach Immunostain pearls and pitfalls Newer non-WHO definition of undifferentiated uterine carcinoma