40-45 y/f with routine examination and normal Pap test two years ago（40-45岁女性，两年前常规检查时宫颈细胞学正常）

ThinPrep Pap

All photos 40x

What is your interpretation and why?

Thanks

 From your questions I can know you all are very thoughtul pathologists. Adenosquamous carcinomas are not uncommon in gynecologic pathology. They account for 5-25% of all cervical ca. They are defined as tumors that contain an admixture of malignant glandular and squamous epithelial components. No creteria mentioned the component should account for ?% of the total tumor volume, like ovarian bordline tumors. 只要两种癌组织都有就可以报. Squamous metaplasia can be present in the cervical endometrioid carcinoma, the same as in endometrial endometrioid ca.  For my case most component is adenocarcinoma, endocervical type, and 20% is squamous cell ca. In the last histology photo 2-3 maligant glands are in the right side and most other epithelial components are maligant low grade squamous carcinoma. In the upper right focal bengin squamous metaplasia may be present.  Wish you will agree with my interpretaion. I will not change my diagnosis even if you do not agree (Joking). I have to review books to anwer your important and sharp questions.

WHO classification:

A. Adenocarcinoma

1.Mucinous ca

encervical type: most common

Intestinal type

Signet ring cell type

Minimal deviation type

Villoglandular type

2. Endometrioid ca

3. Clear cell ca

4. Serous ca

5. Mesonephric

B. Other epithelial tumor

adenosquamous ca

adnoid cystic ca

adenoid basal ca

neuroendocrine tumor

undifferentiated ca

 这就涉及到腺鳞癌和腺棘癌的区别，其实我也有疑问？腺鳞癌：是两种癌成份都有，是不是每种成份要达到一定比例吗？还是只要两种癌组织都有就可以报呢？谢谢老师指点。

看了以上的诊断，仔细阅读7楼组织片，有点疑问想请教赵老师：是伴有鳞癌呢还是鳞化？觉得鳞状上皮细胞有些异型，但不够癌（从提供的图片看）。

 感谢楼主老师精彩病例和点评!!

楼主老师能否抽时间为我们做一次关于AGC的网络讲座?!热切期待中......

 Last week I had a talk  about AGC. I like to share some main points about AGC with friends here.

1. History and Current Situation in the US.

In the 1950s: SCC account for 95% of cervical Ca.

Currently: Incidence of cervical Ca declined markedly, but rate of ADC increased.

Proportion SCC:ADC: SCC 70-75%, ADC up to 20-30% (double)

Increase of ADC mainly in young women

2. SAD Truth

      The incidence rate of cervical ADC never reduced

       Pap test has never been proven effective in preventing cervical ADC

3. TBS 2001 Atypical Glandular Cells

•         AGC

•         -Endocervical cells

•         -Endometrial cells

•         -NOS

•         AGC, favor neoplastic

•         -Endocervical

•         -NOS

•         Endocervical AIS

•         Adenocarcinoma

4. AGC Prevalence

•         Kim TJ et al. Gynecol Oncol 1999;73:292

•         0.07%   (Korea)

•         Geier CS et al. Am J Obstet Gynecol 2001;184:64

•         5.96%  (University of Southern Carolina

5. AGC Prevalence

Summarized 24 studies

2,389,206 Pap

AGC 6829

AGC rate 0.29%

Schnatz PF et al. Obstet Gynecol 2006;107:701

6. AGC Prevalence

•         Bethesda 2001

•         Conventional Pap

–        184 Labs                                    0.45%

•         LBP (LBP-T+S)

–        180 Labs                                    0.37%

–        Davey DD et al: Arch Pathol Lab Med 2004;128:1224

7. AGC Prevalence-my hospital (largest study)

June 2005-August 2007 (27 months)

247,131 Pap

AGC 1021

0.41%

8. AGC Follow-up TBS2001

•         Benign (>60%)

•         -Polyps, endocervical, endometrial

•         -Tubal metaplasia

•         -Microglandular hyperplasia

•         -Endometritis

•         -S/P cone bx

•        

•         Significant lesions up to 38%

•         CIN 2/3, CIN 1

•         AIS

•         Adenocarcinoma

9. AGC Follow-up (U of Kentucky)

•         82 AGC Pap tests (0.15%) (CP, LBC?)

•         -38% significant pathology

–        21% pre-invasive disease (CIN2+ 11%, AIS 8.5%, EH)

–        17% invasive adenocarcinoma (ec-ca 6%, em-ca 11%)

DeSimone, CP et al. Obstet Gynecol 2006;107:1285-91

10. 460 AGC Cases with Preneoplastic or Neoplastic Lesions in Tissue Biopsies (University of Southern California) my study when I was cytopathology fellow

CIN2+                                                 6%

AIS+                                                   4%

Complex atypical hyperplasia+         12%

Ovarian ca                                          1%

Total                                                   23%

Zhao et al. Acta Cytol. 2008 (will be published soon)

11. Histologic Follow-up Study of 662 AGC (TP). My study in current hospital.

•         Squamous lesions (CIN1+)                            23%

•         ---CIN2+         42 (6%)

•         Glandular lesions (AIS+)                               3%

•         Endometrial Lesion                                        8%

•         ---EM-CA   34 (5%)

•         Total                                                               33%

•         Significant                                                       17%

•         PPV for cervical glandular lesion 3%

12. Histopathologic Follow-up of 317 Patients with AEC, AGC-NOS (Cleveland Clinic)

•         Endometrial Lesions              3.8%

•         CIN1                                                   5.0%

•         CIN2+                                                 7.3%

•         AIS+                                                   6.6%

•         Benign                                                            77.3%

•         PPV for cervical glandular lesion 6.6%

•         Chen L &  Yang B. Cancer Cytopath 2008;114:236

13 HPV Positive Rate in AGC (the largest two studies)

•         MWH:                        75/309   24%

My study. 2008 USCAP meeting abstract. I am working on the manuscript

•         Cleveland Clinic         64/317   20%        

Chen L. & Yang B. Cancer Cytopathol 2008;114:236

14. Histologic Follow-up of 317 Patients with AEC, AGC-NOS (Cleveland Clinic)

15. HPV testing to Detect Clinically Significant Lesion (my study)

16. Reproducibility-Interlaboratories, Interobservers

•         There was no consensus for both the origin of the cells and the diagnosis, poor agreement

•         Kappa-type statistical analysis:

&#8226;         Kappa value:<0.4 poor, 0.4-0.7 good, >0.7 excellent

17.  Reproducibility-interlaboratories, interobservers

&#8226;         1. Cytopath 2006;17:353

&#8226;         2. Cancer 2003;99:323

&#8226;         3. Am J Clin Pathol 2002;117:96

&#8226;         4. Am J Clin Pathol 1998;110:653

18. Facts: AGC

&#8226;         0.2-0.5% of Pap results

&#8226;         High incidence of underlying neoplasia (>CIN II, AIS, Cancer)

&#8226;         Common error: following with Paps, missing invasive cancer

&#8226;         Neither HPV testing nor repeat pap is sensitive enough to be used alone as triage

&#8226;         Poor agreement

&#8226;         Poor PPV for glandular lesions

&#8226;         Most interesting (?) AND the most difficult of all cervical cytology

&#8226;         Strongly suggested

&#8226;         PPV is markedly increased compared with Pap only

&#8226;         NPV is very high

19.  When in Doubt

&#8226;         Carefully check clinical data

–         recent pregnancy?

–         patient wears IUD?

–         recent Bx/LEEP?

–        Hx of GYN, radiation, chemo

&#8226;         Second opinion, even though agreement is very poor

20. Balance: Overcall vs Undercall

&#8226;         Misinterpretation is potential delay in patient tx & increased risk for development of invasive ADC

&#8226;         May lead to over-diagnosis of AGC-over treatment

&#8226;         Fine balance to maintain sensitivity and specificity;
pressure to NOT undercall OR overcall

Thank for reading the long mail,

cqz

Forget to send the photos

1. 4x IDC

2. 10x IDC

3. 10x adenosquamous area.

 Very glad to see the interpretaion of above three pathologists. Also notice that few people gave interpretation here. In fact Pap test is the most difficult area in all cytologic areas. AGC is the No 1 difficult of all Pap abnormalities.

These 3 clusters of cells are the only ones with some abnormality. The first impression is that the flat sheets of cells show  increased N/C ratio, round nuclei, a little overlapping. The cytologic features are not very bad. You may consider reactive endocervical cells. Patient did not have any history. Looking carefully you will find the cells are too crowed, called hyperchromatic crowed group (HCG). Dx of atypical glandular cells, endocervical, is very good call.

This pt had bx and hysterectomy. See few photos below. Women had invasive adenocarcinoma with some areas of adenosquamous carcinoma. Pay attention to the cytology of the tumor in histology slides. The nucler grade is low.  

abin译：

非常高兴看到以上三位病理医生的判读。事实上宫颈细胞学是所有细胞学领域中最困难的领域。而AGC则是宫颈异常细胞学中第一难点。

仅有这三簇细胞显示某种程序的异常。第一印象是平铺的细胞显示核/浆比增高，核圆，有些重迭。细胞学特征并不非常恶。你可能考虑反应性宫颈管细胞。患者也没有什么特殊病史。然而仔细看，你会发现细胞太拥挤，称为深染拥挤的细胞团（hyperchromatic crowed group，HCG）。诊断不典型腺细胞，宫颈管型，是很合适的。

这位患者后来经过了活检并切除了子宫。见以下图片，患者有浸润性腺癌伴部分区域腺鳞癌。注意组织学切片上的肿瘤细胞学特点。核级别低。

 Forget to mention that the women was positive for HR-HPV test (HC2) ordered by gynecologist , HPV testing for women age >30 y.

（补充：HPV阳性）