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肉眼检查: |
40-45 y/f with hx of cervical ca with radiation, chemotherapy, ovarian mass 11 cm. I did frozen. Gynecologist came to frozen room to sit with me to read frozen slide.
What can you tell your surgen about the case if your were the pathologist?
What is your differential dx?
I ordered IHC in frozen block and will know basic result tomorrow.
abin译:
20分钟前的卵巢肿瘤冰冻切片。我们能告诉妇科医生什么?
40-45岁女性,有宫颈癌病史和化疗、放疗史。卵巢肿块11cm。我做冰冻切片,妇科医生跑到冰冻室,和我坐在一起看冰冻切片。本例,如果你是病理医生,你能告诉手术医生什么?
你的鉴别诊断是什么?
我用冰冻切片做了免疫组化,明天会知道基本结果。
Thank Dr. wq_9603 for your excellent translation.
When we do frozen we must choose one of the three to write in our frozen report---1) benign, 2) defer, 3) malignant. "Defer" means that pathologist can not make definite diagnosis (benign or malignant). In other words pathologists are not sure of the nature of the lesions. The lesions can be benign, but also can be malignant.
I do not know how to translate the "defer". Is " 延迟发报告" good words?
To Dr. Zhang,
Thank you for your great discussion for some cases. It is great to have some communication with you in the web.
I guess Zhang is your last name and you are from Shandong. I was from Qingdao Medical School. If you graduated from the medical school in shandong we may be schoolmate, or at least we are Shandongness.
As I mentioned in the begining I reported my frozen as malignant for this case. However I had a long discussion with gynecologist during the frozen. He mentioned that he would do staging for this women even I defered the case. I documented this exactly. Even though I made wrong interpretation it did not cause harm to the patient. So I am ok. In fact I showed the frozen section in our dept conference. Every one though it was a granulosa tumor or metastatic tumor. Anyway we know our limitation. What can we do? Maybe we should have more defered cases for frozen. Surgeons will not be happy. Maybe we should take more sections for frozen.
Ok, this is.
Thank Dr. Zhang for your reminding this case. Sorry I thought I have put here our interpretaion. In fact i did not. However I listed all IHC results in the floor 27.
Based on the morphologic features and IHC results this is an ovarian sex-cord stromal tumor. The differential dx includes granulosa cell tumor and fibroma/thecoma tumor. If you read the true glass slides it is easy to tell it is a fibroma/thecoma tumor, but not granulosa cell tumor. IHC results also support the dx of fibroma/thecoma. I showed the case in our department slide showing conference. All pathologists agree with the interpretaion. Now the question is that this tumor should classified into ?subgroup of fibroma/thecoma group. As what I and other people discribed before the tumor had some features of sclerosing stromal tumor and also some features of thecoma. However, it is not a typical sclerosing stroma tumor, nor typical fibro-thecoma. Finally I released the case as ovarian stromal tumor with features of sclerosing stromal tumor and thecoma with a long comment. The key for this case is that it is a benign ovarian stromal tumor. The case was also discussed in our weekly gynecologic tumor board. gynecoogists felt satisfacted for the dx. The patient will get close follow-up.
A resident did the literature search and noticed that 115 cases of sclerosing stromal tumor (SST) was reported since the initial report. The mean age for SST is 27 or 28 year. All SSTs have been clinically benign in reported cases. None of these cases reported had the lobular ca-like cytomorphology. She is working on and trying to write a case report for this case.
I just told you our interpretation for this case. It does not mean that it is a correct or final diagnosis for your guys. You can have your own interpretation.
Thank all of you for attending the discussion and reading this case.
cz
About paper from Dr.Oliva and Young (MGH) is the best paper to describe the morphologic features of SCT. You should read the full paper several times if you want to know the morphology of SCT.
If some one is interested and cannot find the paper, tell me email and I can email you the full paper.
James Wright Pathology Laboratories, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA. eoliva@partners.org
Ovarian Sertoli cell tumors are rare, and their morphologic spectrum, behavior, and factors influencing the latter are not clearly established. They may be mimicked by many different tumors, some of them more frequent than Sertoli cell tumors; immunohistochemistry may aid in this differential, but its role has not been analyzed in a large series. We studied the clinicopathologic features of 54 Sertoli cell tumors, including the immunohistochemical profile of 23 of them. The patients, 6 of whom had Peutz-Jeghers syndrome, ranged from 2 to 76 years of age (mean, 30 years). Eleven patients had estrogenic and 4 had androgenic manifestations. The tumors ranged from 0.8 to 30 cm, with the majority being in the range of 4 to 12 cm. They were all unilateral, usually solid, and often yellow. The predominant microscopic pattern was tubular, seen, albeit often only focally, in all tumors; other patterns were cords or trabeculae (28), diffuse (21), pseudopapillary (4), retiform (3), islands or alveolar arrangements (3), and spindled (3). The tubules were solid or hollow with the former being somewhat more common. Delicate septa were occasionally seen and were conspicuous in areas of one tumor. The stroma was abundant in 15 tumors with marked sclerosis in 4. The cells usually had pale to occasionally densely eosinophilic cytoplasm, but 6 tumors were composed of cells with prominent foamy cytoplasm, falling in the category of "lipid-rich" Sertoli cell tumor, and one had cells with clear non-foamy cytoplasm. Forty-four tumors were stage I (42 of them were stage Ia and 2 were stage Ic), 1 was stage II, 3 were stage III, and 6 were not adequately staged. Follow-up was available for 27 patients with stage I tumors, and all were alive and well at last follow-up except for 2 patients with stage Ia and 1 with stage Ic disease. Those 3 patients had pelvic-abdominal recurrences 18, 36, and 9 months, respectively, after the initial diagnosis. Two of the three clinically malignant stage I tumors had moderate to severe cytologic atypia and brisk mitotic activity (>5 or more mitoses/10 high power fields [HPFs]), and one of these had tumor cell necrosis. Among the 10 clinically benign stage I tumors with more than 5 years of follow-up, only 3 had >5 mitoses/10 HPFs, but none had more than mild cytologic atypia and none had tumor cell necrosis. Two of the three patients with stage III disease had follow-up information and one was alive at 16 months and the second developed splenic metastases 2 years after the initial diagnosis. Two of the three stage III tumors had at least moderate cytologic atypia and brisk mitotic activity. Immunohistochemical stains showed positivity for AE1/3-Cam5.2 in 15 of 23 tumors; Epithelial membrane antigen (EMA) was negative in all the tumors. Inhibin was positive in 18 of 22 tumors, calretinin in 10 of 20, CD99 in 19 of 22, vimentin in 17 of 18, smooth muscle actin in 4 of 18, neuron specific enolase in 8 of 16, S-100 in 2 of 20, and chromogranin was negative in all 21 cases studied. Although Sertoli cell tumors usually have a distinctive tubular pattern that facilitates the diagnosis, other patterns may occasionally predominate, causing confusion with various other primary and metastatic ovarian tumors. EMA, inhibin, and chromogranin represent the most helpful triad of immunomarkers serving to exclude two common mimics of Sertoli cell tumors (endometrioid carcinoma [inhibin-; EMA+; chromogranin-] and carcinoid tumor [inhibin-; EMA+; chromogranin+]). Although CD99 and calretinin are often expressed in these tumors, they are much less specific and not as helpful in the differential diagnosis. Most Sertoli cell tumors are stage I, unilateral, cytologically bland, and clinically benign, but occasional examples are high stage, and about 11% of stage I tumors have worrisome histologic features that may portend an adverse outcome. The tumors typically occur in young females, sometimes children who typically present with sexual precocity, and occasional patients have Peutz-Jeghers syndrome.
Above table is my another previous study. Inhibin is positive in 39 of 40 pure sertoli cell tumors.
My study (floor 44) indicated WT1 are positive in sertoli cell tumor, but this case is not a sertoli cell tumor.
Why?
1. Mrphologic features do not support the diagnosis of Sertoli cell tumor. Tubules are most common structure in SCT. It can be found in all SCT if you take more sections. SCT can have many different growth patterns. my current case do not show any cytomorphologic feature of SCT.
2. IHC results do not support SCT, negative inhibin. Of cause negative inhibin is not the only reason to rule out SCT.
TABLE 2: Overall positivity for alternative and traditional immunohistochemical markers
Antigen |
Sertoli cell tumor |
Endometrioid borderline tumor |
Sertoliform endometrioid carcinoma |
Well-differentiated endometrioid carcinoma |
Carcinoid tumor |
Epithelial markers
CK7* |
13% |
100% |
85% |
100% |
24% |
ER* |
8% |
87% |
85% |
89% |
2% |
PR* |
13% |
84% |
77% |
93% |
2% |
Pan-CK† |
65% |
100% |
100% |
100% |
98% |
CK8/18† |
43% |
100% |
93% |
96% |
74% |
EMA† |
0% |
100% |
100% |
100% |
12% |
Sex cord markers
CD10* |
25% |
39% |
31% |
37% |
9% |
Inhibin† |
98% |
0 |
0 |
4% |
2% |
Calretinin† |
60% |
11% |
0 |
18% |
0% |
CD99† |
68% |
16% |
23% |
33% |
40% |
Neuroendocrine markers
CD56* |
48% |
16% |
16% |
30% |
57% |
Synaptophysin† |
35% |
8% |
8% |
22% |
98% |
Chromogranin† |
13% |
3% |
15% |
11% |
100% |
Zhao C, Bratthauer GL, Barner R, Vang R.
Comparative analysis of alternative and traditional immunohistochemical markers for the distinction of ovarian sertoli cell tumor from endometrioid tumors and carcinoid tumor: A study of 160 cases.
Am J Surg Pathol. 2007 Feb;31(2):255-66
This is a challenge case. When I first pasted the frozen photos here I did not know it would be so complicated case.(这是具有挑战性的病例。当我最初上传冰冻切片时,我不知道它会如此复杂)
It is more difficult for your guys to evaluate the case only based on a few photos.(你们仅根据几张图作出评价会更加困难)
All all agree that this tumor belongs to the category of ovarian sex cord-stromal tumor (SCST), the area I love. I did a lot of IHC studies on scst. I think my seral IHC studies are the most detailed and the most large studies in the world. (所有人都同意它属于卵巢性索-间质肿瘤<SCST>,这是我喜爱的领域。我对SCST做过很多研究。我认为我的几个研究是目前最详细最大宗病例的研究。)
SCSTs include tumors from sex cord and stromal components. There are no classic features of granulosa tumor for my case. Also think about. Did you see the CD99 and inhibin pure negative granulosa tumors in your practice or text books? Leydig cell tumors should be strongly and diffusely postive for calretinin and inhibin, and negativ for WT1. I once reviewed about 300 cases of ovarian pure sertoli cell tumors and sertroli leydig cell tumors for research. But no one like this case.
Now I hope you review all photos and IHC again to think it is a sex cord tumor or stromal tumor.
(SCST包括来自性索和间质成分。我这一例没有典型的粒层细胞瘤特征。也考虑一下,你在实践中和书本上见过CD99和inhibin完全阴性的粒层细胞瘤吗?Leydig细胞应该呈calretinin和inhibin弥漫强阳性,而WT-1阴性。为了研究,我曾经回顾过300例左右的Sertoli细胞瘤和Sertoli-Leydig细胞瘤。但没有一例像本例这样的。现在我希望你们再回顾一下所有图片和IHC,思考一下它是性索-间质肿瘤还是间质肿瘤__abin译)
For this case, inhibin and CD99 are purely negative. Also if you read the photos carefully you will notice there are no typical features of granulosa cell tumors. Why did most people still think it is a granulosa tumor?
abin译:本例,Inhibin和CD99完全阴性。如果仔细看HE切片,你也会注意到,它没有粒层细胞瘤的典型特征。为什么大多数人仍然认为它是粒层细胞瘤?
This is the table of my IHC study result.
Zhao C, Vinh TN, McManus K, Dabbs D, Barner R, Vang R. Identification of the Most Sensitive and Robust Immunohistochemical Markers in Different Categories of Ovarian Sex Cord-stromal Tumors.
Am J Surg Pathol. 2009 Mar;33(3):354-366
Tumor |
WT1 |
SF-1 |
MART-1 |
Inhibin |
Calretinin |
CD99 | |
Adult Granulosa Cell Tumor (n=32) |
78% |
100% |
- |
94% |
81% |
88% | |
Sertoli Cell Tumor (n=27) |
100% |
100% |
- |
96% |
48% |
59% | |
Sertoli-Leydig Cell Tumor (n=18) |
SC, total |
100% |
100% |
- |
94% |
44% |
50% |
SC, WD |
100% |
100% |
- |
100% |
25% |
50% | |
SC, ID |
100% |
100% |
- |
93% |
50% |
50% | |
LC, total |
- |
100% |
94% |
100% |
100% |
6% | |
Steroid Cell Tumor (n=25) |
- |
100% |
96% |
100% |
100% |
32% | |
Fibroma/ Fibrothecoma (n=25) |
Total |
100% |
100% |
- |
56% |
36% |
- |
F |
100% |
100% |
- |
50% |
25% |
- | |
FT |
100% |
100% |
- |
80% |
80% |
- |
Key: F, fibroma (n=20); FT, fibrothecoma (n=5); LC, total, Leydig cell component (all Seroli-Leydig cell tumors combined); SC, ID, Seroli-Leydig cell tumor of intermediate differentiation (n=14); SC, total, Sertoli cell component (all Seroli-Leydig cell tumors combined); SC, WD, well-differentiated Seroli-Leydig cell tumor (n=4); and -, No expression.