Astonishing case in this young woman!

Morphologically it has very ominous looking and likely we are dealing with a malignant neoplasm. Questions are where it is from and what is the histologic type. The differential dx can be broad for a tumor with oxyphilic cytoplasm in a young woman. Let's concentrate on primary and secondary tumors that can or often occur in this young age in peritoneal/pelvic cavity with oxyphilic features.

Primary Tumors:

1) Hepatoid variant of yolk sac tumor (YST): Usually seen under 25 year old woman. You shoud search other areas to see if there is classic reticular pattern of YST. IHC can include AFP.

2) Deciduoid mesothelioma (黄体样恶性间质细胞瘤） This is my first response to the photos you posted. DM is a rare variant of malignant mesothelioma which has the following characteristics.

- It tends to occur in young woman, mean age is around 30 and most cases reported were under 40.

- It occurs mainly in peritoneal/pelvic cavity, lessly seen in plerual cavity

- It often has no history of asbestos exposure

- it is highly malignant and aggressive with very dismal prognosis.

Please do following IHC to exclude this entity: Calretinin, CK5/6, WT-1, CK7/20

3) Hypercalcemic-type Small cell carcinoma (SCC-Ca): There is a large cell variant of this tumor. Actually it is a misnomer since most cases are "non-small cell".Mean age for SC-Ca is 24 years. Clinically patients often (2/3) have high level of blood calcium. This is a very aggressive tumor with dismal prognosis, especially when occurs in <30 year old women. It  belongs to neuroendocrine tumor category. Therefore, it should be focally positive for chromagranin and synaptophycin. But be careful, since SCC-Ca can be also positive focally for cytokeratin, EMA and vimentin.

4) Lutinized juvenile granulosa cell tumor (JGCT):  Morphologically this case is too malignant-looking for JGCT. But You should search around to see if see some typical JGTC pattern and also focal cytoplasmic clearing. Since this tumor is also positive for calretinin, therefore, inhibin should be added when entertaining differential with JGCT.

5) Lutinized steroid cell tumor: very rare

6) Apocrine carcinoma or pituitary-type tumor in a dermoid cyst (teratoma): I never seen myself, but heard about them in literatures.

7) Large cell and anaplastic lymphoma: She is too young for this malignancy, but need to rule out.

You can add CD20 and CD30 markers in your second round IHC staining panels, if rule out first two diagnoses.

Secondary tumors:

1) Krukerberg tumor, often metastatic from an incipient poorly differentiated adenocarcinoma of the stomach. Patient should have digestive symptoms and often weight loss (non-specific in this case). Gastric biopsy can be easily missed or negative. This cancer is the most missed disease in GI biopsy acclaimed by Dr. Juan Rosai in his book! It is very sneaky and often have visceral organ and peritoneal cavity metastasis before identify primary cancer in stomach! You need check her clinical history and information. 

There is really no difinitive IHC markers for stomach cancer.  Cytokeratin markers can be helpful.

2) Metastatic melanoma:  Less likely in this young Chinese woman, but need rule out anyway. You can add melanoma markers in this case to rule out.

3) Carcinoid tumor: Sometimes can be oxyphilic and should be rule out.

wdw7925译：

发生在年轻女性中的一例令人吃惊的病例，在形态学上这个肿瘤具有恶性特征，我们可能会按恶性肿瘤来诊断，问题是如何判断肿瘤的来源及组织学类型。鉴别诊断应该囊括在年轻女性中出现胞浆嗜酸性的肿瘤。我们应关注在年轻人腹腔和盆腔中经常发生的具有嗜酸性特征的原发和继发肿瘤。

  原发性肿瘤：

  1）肝样卵黄囊瘤：经常发生于25岁以下的女性中，观察其他区域是否具有卵黄囊瘤典型的网状结构，免疫组化包括AFP。

  2）黄体样恶性间质细胞瘤：这是我对上传图片的第一反应。黄体样恶性间质细胞瘤是一种罕见的恶性间质细胞瘤并具有以下特征：

  一般多发生于年轻女性，平均年龄在30岁左右，大多数报导的病例在40岁以下；肿瘤多发于腹腔和盆腔，很少发生于胸腔；患者通常没有石棉接触史；这种肿瘤的恶性程度高，侵袭性强，预后十分不好。免疫组化排除诊断包括：Calretinin, CK5/6, WT-1, CK7/20。

  3）高血钙型小细胞癌：这种肿瘤中含有不同的大细胞，实际上这是一个误称，因为大多数病例是“非小细胞”。平均发病年龄在24岁，临床病人通常血钙浓度很高。这种肿瘤具有极高的侵袭性和很坏的预后，尤其是发生于30岁以下的女性时更为明显。它属于神经内分泌肿瘤，因此在免疫组化中嗜铬蛋白和突触素表达应该局灶阳性，注意一点，在cytokeratin, EMA and vimentin上也可呈局灶性阳性表达。

   4）黄素化幼年型颗粒细胞瘤：这个肿瘤图像在形态学上对于幼年型颗粒细胞瘤来说恶性特征有些过高了，但是也应该寻找是否具有幼年型颗粒细胞瘤的典型结构和局灶透明的细胞质。如果这个肿瘤在calretinin上表达阳性，那么inhibin也需要加入进来与幼年型颗粒细胞瘤相鉴别。

   5）黄素化类固醇细胞瘤：很少见。

   6）在良性畸胎瘤中的大汗腺癌或垂体型肿瘤：我自己从未见过，但在文献中有过报导。

   7）大细胞和间变淋巴瘤：对于这种淋巴瘤，患者的年龄显得过于年轻，但也需要排除。可以在第二轮的免疫组化染色板上加入CD20和CD30做为标记物，首先就要排除这两个诊断。

  继发性肿瘤：

1）Krukerberg瘤：通常转移来源于胃的原发性低分化腺癌，患者常伴有消化道症状并消瘦明显，胃的活检容易被错过或忽视。Krukerberg瘤最容易错过对胃的活检，这一点在Juan Rosai 博士的书中得到认同。这种肿瘤发病隐匿，通常在鉴定出胃的原发肿瘤之前，就已经在内脏器官和腹腔发生了转移，这就需要查看临床病史和相关信息。对于胃癌诊断目前还没有确切的免疫标记物，但Cytokeratin对于诊断有帮助。

2）转移性黑色素瘤：在中国年轻的女性中很少见，但也需要排除诊断。可以加一些黑色素瘤的标记物用于鉴别诊断。

3）类癌：通常也是嗜酸性的，也需要鉴别排除诊断。

This is a very large malignant neoplasm of ovary in a young woman. Metastasis is never easy to exclude, but at 1ge 25 I think it is unlikely. In primary ovarian malignancies, I would put small cell carcinoma of ovary, hypercalcemic type, as my first choice. This is a very rare and very aggressive malignancy in young women. Not all patients have presurgical hypercalcemia. Immunohistochemistry of the reported cases has been nonspecific (consistent expression of one or two common epithelial markers and inconsistent expression of various neuroendocrine markers) and helps more in ruling out differential diagnoses (metastatic melanoma, metastatic carcinoma [e.g., breast], malignant mesothelioma, hepatoid carcinoma) than any thing else. So a definitive diagnosis of this eneity relies very much on histopathology, aided by clinical history, presurgical serum level of calcium, and exclusionary immunohistochemistry. Because of this, a few reknown pathologists have described its histopathology well. Look for (1) two cell types (one smaller with little cytoplasm, and the other larger with plump eosinophilic of amphophilic cytopasm; both types of cells have single prominent macronucleoli and vesicular chromatin pattern; if large cells predominate, it is known as the "large cell variant" of small cell carcinoma of hypercalcemic type), (2) follicle-like spaces containing pale eosinophilic fluid, and (3) very focal collections of cells containing cytoplasmic mucin (shown by mucicarmine stain). The most authoritative paper on this entity is somewhat old but still extremely useful - Young RH, Oliva E, Scully RE. Small cell carcinoma of the ovary, hypercalcemic type. A clinicopathological analysis of 150 cases. Am J Surg Pathol 1994 Nov;18(11):1102-16.

淡茶译：

这是一例年轻女性的巨大卵巢恶性肿瘤。转移性癌不易排除，但我认为25岁的年龄不大可能发生。在卵巢的恶性肿瘤中，我首选高钙血症性小细胞癌。这是一种年轻女性的罕见而高侵袭性的恶性肿瘤。并不是所有的病人都有外科手术前的高钙。在所报道的病例中，免疫组织化学不具有特异性（一两种普通上皮标记的一致表达以及各种神经内分泌标记的不一致表达），而免疫组化在排除鉴别诊断（恶黑，转移癌（比如乳腺癌），恶性间皮瘤，肝细胞癌）时更有帮助。因此最可靠的鉴别更多的依赖于组织病理学，（也需）借助于临床病史、外科手术前的高血钙和免疫组织化学的排他性诊断。一些病理学家很好的描述了它的组织病理学：1　两种细胞（较小者胞浆少，较大者有双嗜性宽胞浆，两者都有单个的大细胞核和vesicular泡状？？染色质）。如果以大细胞为主，则称作“大细胞亚型”。2　follicle-like spaces滤泡样结构？？包含嗜酸性小体。3　局灶的细胞团含有胞质的粘蛋白（粘蛋白胭脂红可证实）。此病的最具权威的报道虽在某些方面有些陈旧，但仍然非常有用――Young RH, Oliva E, Scully RE. 卵巢高钙血症型小细胞癌. 150例临床组织学分析. Am J Surg Pathol 1994 Nov;18(11):1102-16.

    第一次翻译这么复杂的东西，如有不当的地方请包含指正。

楼主您是觉得年会诊断不妥才上传的吧，谢谢这么好的病例。

 又是一个少见疑难病例，学习。

 A very challenging case indeed!

 I liked the differential diagnosis posted by Dr. Yang and mjma. It is very thorough. The small cell carcinoma of the hypercalcemic type is a very good thought. Basically this case need some immunostains to rule out or rule in lymphoma, deciduoid mesothelioma, metastatic carcinoma, and melanoma. I just want to add the following: we all know that WHO classify primary ovarian tumors into the following 3 broad categories: 1) surface epithelial tumor; 2) sex-cord stromal tumor; and 3) germ cell tumor. Considering the age of this patient, the later two categories are more likely. The morphology is not quite fit any obvious sex-cord stromal tumor, thus immunostains for germ cell tumor need to be added. On low-power, the histology shows a corded appearance with some edematous stroma which make you think about dysgeminoma, but it lacks the typical lymphoid infiltrate or granuloma, also the mitotic figures are too much. Embryonal carcinoma is exceedingly rare. Please add PLAP, OCT-4, CD117, EMA, and CD30 in your work-up. Another suggestion is to sample the mass extensively, at least 1 cm per section. Please keep us posted. Thanks you

学习

学习了

 to  Dr.杨斌：

Deciduoid mesothelioma (黄体样恶性间质细胞瘤）

对应的中文似应为：蜕膜样（恶性）间皮瘤？谢谢！