I'm on my way out of town and I get back until last night. So I went back in my files and this is some slides I pulled out of a lecture that I recorded on the SGO website about seven years ago. So some of the immunos may be a little dated, but I think all the principles are the same. I think it'll work fine for what we want to do. He asked me to talk about tumors metastatic to the ovary. Before we do that, I thought it might be entertaining to briefly review primary ovarian tumors with respect to what their cell of origin is. Most ovarian tumors, all primary ovarian tumors come from one of three cell types, epithelial, germ cell, and sex-coordinated stromal cells. Of course, the epithelial cells, tumors derived from epithelial cells compose a great majority of all ovarian tumors, both benign and malignant. The overall frequency of anywhere from 65 to 70 or more percent in epithelial tumors comprise at least 90% of malignant ovarian tumors. Tumors derived from germ cells account for 15 to 20% of ovarian tumors. The great majority of those being simply benign cystic teratomas, 3 to 5% of those are malignant. The remaining sex-coordinated, the remaining ovarian tumors are derived from sex-coordinated stromal cells. So the great majority of all primary ovarian tumors are epithelial in origin. That's completely different from what we see in the ovarian counterpart in the male, which of course is the testes. In the testes, most primary tumors by far and large are germ cell derived. Most of those are dysgerminomas. I mean, I'm sorry, I'm assuming all those in the male. Most male testicular tumors are germ cell in origin. Epithelial tumors are unknown almost in testicle, the remainder of them being sex-coordinated stromal tumors. Back to ovarian tumors, about 5% of all ovarian tumors are metastatic. From other sites. And that's what we're going to, we're going to talk about here just briefly, about 5% of ovarian tumors are metastatic tumors. Tumors that spread to the ovary are sometimes subdivided into two categories, which are completely artificial. One is considered metastatic, which is tumors spread from distant sites, such as colon, breast, et cetera. And then one terminology divides them into a secondary type of tumor, which tumors spread from adjacent sites, such as uterus, organ tube, et cetera. This distinction is completely arbitrary and artificial as all of these are metastatic tumors. I'm going to confine myself and what I'm going to talk about for the next few minutes into tumors which are spread from distant sites. I'm not going to talk about tumor spread from the ovary, opposite ovary or the uterus or endometrium. That could be a subject for another talk later. Most common primary sites of tumor which spread to the ovary are colon, appendix, stomach, and breast. And of course tumors from adjacent sites such as endometrium, opposite ovary, primary peritoneal carcinoma. We're going to confine ourselves to those spread to the ovary from distant sites. Features of metastatic ovarian lesions, they're bilateral in about 70% of the cases. Bilaterality increases the chance that the lesion is metastatic. These tumors may involve the surfaces of the ovary and or the tube and not the deeper parenchymal tissues at times, although exceptions that certainly occur. You can see metastatic lesions which completely destroy the ovary and the tube. You see that, but often that's just the surfaces of the ovary, which is involved. Metastasis of the ovary occurs by several mechanisms. You can have hematogenous spread, you can have lymphovascular spread, you can have direct extension, or you can have transcylonic spread. This is a case of metastatic colon carcinoma. All these cases which I'm going to present, three or four cases, are cases which we saw at my institution and which were presented at Tumor Board. This lady was about 60 years old and she presented with bilateral ovarian tumors and no other history at the time, just ovarian tumors bilateral. Looking at the tumor just quickly, we get a very superficial, quick impression that, yeah, this looks kind of like maybe an endometrioid adenocarcinoma. But if you look at it more closely, you start to see goblet cells with a lot of mucin. This would be unusual in an endometrioid carcinoma. You also see, if you look at the mucin, you see what we refer to as dirty mucin. This is mucin infiltrated with acute inflammatory cells and the chronic debris, a pattern referred to as dirty mucin. If you look again at the glands, there's a large glandular structure, but within the large structure are smaller glandular structures. We call this a cribriform pattern or glands within glands. A combination of goblet cells, a cribriform or gland within glands pattern, or glands with dirty mucin. These three things are a little unusual in endometrioid carcinoma and justify going further on with the workup and this, you know, his chemical stains, which were done on this case. We did a CK7, which was negative. We did a CK20, which was positive. We did a CDX2, which is a GI marker, which is positive. We had a PAX8, which is a malaria marker, which was negative. So this pattern strongly supports metastatic carcinoma of colon. Had it been an endometrioid or serous ovarian carcinoma, we would expect the CK7 to be positive, CK20 negative. We got the exact opposite. We were also expected the PAX8 to be positive, but in our case, it was negative. And we would expect the CDX2 to be negative. In our case, it was positive. So even his chemistry certainly supported this being a primary colonic origin. You think, well, if it's mucus, maybe it could be a mucus ovarian primary. But in that case, you also expect the CK7 to be positive as well as the CK20. And you expect the PA, the PAX8 to be positive. In our case, it was negative. So this certainly was consistent with a colonic primary carcinoma. Next case, this lady presented with, again, an ovarian mass, a bilateral ovarian mass. What you see here are scanned images of the actual glass slide, a 1X magnification, if you want to think of it that way. And you can see here the right ovary, there is surface involvement by a tumor producing a lot of mucin. There's not a lot of deep parenchymal involvement. A lot of this is on the surface. Certainly there's some parenchymal invasion, but the bulk of the tumor is on the surface and the overall architecture of the ovary is preserved. Histologically, if you look at this tumor, we can see it's a mucinous tumor. It's predominantly on the surface of the ovary producing abundant mucin, some free mucin within the ovarian strome as well. This tumor is also metastatic to periaortic lymph nodes, as you can see here. So this prompted us to do an immunohistochemical workup. Our CK7 was negative, CK20 was positive, CDX2 was positive, PAX8 was negative. So that's certainly strongly supportive of a chronic adenocarcinoma. After we suggested this to the clinicians, well, again, here's our, here's our immunohistochemical results, certainly consistent with chronic adenocarcinoma. We talked to the clinician about this and they went back and, examined her and did a colonoscopy on her, found she had a colonic mass arising from colonic mucosa. She also subsequently went through additional surgery. Here's her appendix, which is certainly in a lot of cases, the primary site of metastatic mucinous carcinoma of the ovary. In this case, the appendix was negative. Here is a section of her colon showing adenocarcinoma arising from colonic mucosa. Here's a deeper section, deeply invasive into the muscularis. Once it got down here it started producing abundant mucin. This is a mucinous chronic adenocarcinoma, which exhibited transmural invasion out into the mesentery, also metastatic to a mesentery lymph node. Krukenberg tumor, the case we talked about tonight, these were classically described as metastatic gastric carcinomas with signet ring features, which metastasize to the ovaries. That's the classic definition of a Krukenberg tumor. We talk about signet rings. Here's an actual signet ring in the center. It gets its name from the fact that in old ancient medieval days, when people dealt with wax seals and things, they would have an identifying ring that they could actually press into the sealant document, which officiated this as a document being released by them. You can see how signet cells get their name. Here's a higher power view of the signet cell. It looks very much like the signet ring. You can look over here at more signet ring cells, and you can see exactly how it gets its name. They look very similar to a signet ring, so signet ring carcinoma. These are now generally considered to include any ovarian metastatic adenocarcinoma with a component of signet ring cells, which makes up at least 10% of the lesion. So we have expanded the definition of a Krukenberg tumor to any ovarian metastatic adenocarcinoma with at least 10% signet ring cells in it. 70% or more of these tumors are gastric primaries. Other primary sites include more frequently appendix, colon, gallbladder, filiary tract, or breast. Less frequency, you can see signet ring carcinoma is a metastatic from pancreas, urinary bladder, cervix, or renal pelvis. So this lady has a metastatic signet ring adenocarcinoma, and so we found out she had a history of a gastric primary. As Lana said earlier, we see here in the United States, at least we see a lot of metastatic breast carcinoma to ovary. Here's an example. This is a classic example of metastatic carcinoma of breast. What you see classically are these single file cords, the cells infiltrating into the stroma. This is an infiltrating ductal carcinoma. This pattern is very, very suggestive no matter where you see it in the body, a metastatic ductal carcinoma. It's classic infiltrating pattern. Again, higher power and you can see here a single file line of cells infiltrating into the stroma. That pattern is always very suggestive metastatic breast carcinoma when you see it. Another thing that we occasionally see, but not very frequently, is metastatic melanoma. Of course, melanoma is a great imitator. It can resemble many other tumors. Classically, melanoma presents as a solid sheet of loosely cohesive cells. In visual cells, they have large macronucleoli. So this is a pattern suggestive of melanoma. Here's a higher power view showing a macro or a very large nucleolus within the nucleus. Other things you see are nuclear pseudo-inclusions. This we see here, where I'm pointing here, they see three pseudo-inclusions in the nucleus. They're actually cytoplasmic inclusions into the nucleus. We call those nuclear pseudo-inclusions. So we see that pattern. You start thinking of melanoma and of course, you got to follow that up with chemistry and that's what we're doing in this case. HMB45 and Mark 1 are good immunohistochemical markers of melanoma. In this case, both were positive. When I saw this pattern on HNA, I called the clinician and I talked to him and I told him that, you know, this was suggestive of melanoma, that we were going to have to do immunos and for him to go back and take some additional history from her, which he did. And subsequent history revealed that she had had a malignant melanoma removed from her ear two years previously. From the time, three months after she had the surgery was produced, this specimen, she died of widespread melanoma. Metastatic carcinoid tumor is something we occasionally see in ovary. In this case, here's a lady who presented with a ovarian mass and a tumor exhibits what we refer to as a geographic pattern. It looks like you're looking at a map from a distance, a geographical pattern. In higher power, tumors composed of sheets of tumor cells, which have a mixture of dark and light nuclei. We call it a salt and pepper pattern. This suggests a neuroendocrine differentiation. Neuroendocrine tumors are carcinoid tumors of the ovary or anywhere else in the body. There's a spectrum of these tumors. From the typical carcinoid pattern, showing an organoid pattern, which you can see little clandrel-like structures, all the way over to the more malignant version, a small cell carcinoma, a neuroendocrine carcinoma, which occurs both in a small cell variety and large cell variety. This lady's tumor is somewhat in between the two. We call this an atypical carcinoid or an intermediate carcinoid tumor. The geographic pattern, salt and pepper nuclei, suggests neuroendocrine differentiation. So we need to confirm neuroendocrine histochemistry, which we did. We used synaptophycin and chromogranin to immunohistochemical stains, neuroendocrine differentiation. Both were strongly positive results, confirmed neuroendocrine differentiation, an atypical neuroendocrine tumor. In the ovary, what confuses things in the ovaries when you see neuroendocrine tumors or carcinoid-type tumors is that they can also be primary to the ovary. When they're primary, they're usually unilateral. With a metastatic, they're usually bilateral. Primary carcinoid tumors of the ovary often exhibit teratomatous elements. They're considered a form of germ cell tumor. If they're metastatic, you don't see a teratomatous element. Primary, they're usually confined to the ovary. Metastatic, you get abdominal metastases frequently. If they're primary, they're present within ovaries as a single mass or a cyst. If they're metastatic, they're usually multinodular. The other interesting thing is primary carcinoid tumors of the ovary don't generally produce carcinoid syndrome, whereas metastatic carcinoid tumors of the ovary, about 50% of these cases, these women clinically have a carcinoid syndrome. Lymphoma is another tumor that we see occasionally in the ovary. Here's a lady who presented with both ovarian masses and a urinary bladder mass. Physiologically, the tumor was composed of just sheets of apparent lymphoid cells, small round cells. These were everywhere. They were in the right and left ovary and fallopian tube, also within a pelvic mass. The routinely stained sections strongly suggested a diffuse lymphoma. We did image chemistry, did what's called a leukocyte common antigen, which is sort of a generic marker of lymphoid differentiation that was positive. Follow that up by CD20, which is specific for B cells and CD3 specific for T cells. T cells are essentially negative, B cells strongly positive. So she was diagnosed with a large B cell lymphoma thought to be primary within her urinary bladder. What I didn't talk about was metastases from endometrial carcinoma or from contralateral ovarian carcinomas or tubal carcinomas or primary peritoneal carcinomas. Those can be very confusing sometimes. You get a metastasis from endometrial carcinoma to an ovary. Then you're left with the dilemma of trying to decide, is this endometrial primary metastatic to the ovary? Is it ovarian primary metastatic to the endometrium or is it synchronous primaries? That itself can be subject to another complete talk. But I thought I would show those as examples of some of the more common metastatic tumors that we see to the ovary. And with that, I will stop sharing my screen and turn it back over.

tumors metastatic to the ovary

primary ovarian tumors

metastatic tumors

colon, appendix, stomach, breast

diagnostic challenge