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- 2012年第38期——双侧卵巢肿块（已点评）
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53 y/f with bilateral adnexal masses and anterior abdominal wall nodule and peritoneal effusion. Regular CT examination showed bilateral ovarian masse measuring 10 and 8 cm, respectively; lung negative, pancrease, gastric negative findings also. Patient has no previous malignant history.
《永恒爱恋老师友情帮助翻译》：女，53岁，双附件巨大肿块，之前有腹部质硬结节伴腹膜渗出物；CT检查示双侧附件巨大肿块，大小分别约为10cm和8cm，肺、胰腺、胃均无异常发现，患者无恶性肿瘤病史。
Core biopsy was performed for anterior andominal wall nodule.
行腹部质硬结节细针穿刺活检
Three core biopsy specimen showed benign fibroadipose tissue. Only one core demonstrate focal epithelial lining.
See the photos：
见图：
40x
100x
200x
400x
Please descript
请描述
1. Your analysis and impression for this core biopsy
1、您对此穿刺活检标本的分析和看法
2. If you want to order some stains, what stains will you order? Only three unstained slides are avaiable due to the scant tissue.
2、如果您觉得需要做免疫组织化学染色，会选择哪些标记，剩余的组织只可用来做三张染色。
本例点评：赵澄泉老师
（以下由：蔷薇老师友情帮助翻译！）53岁女性，双侧附件肿块，前腹壁结节，有腹水。常规CT检查显示双侧卵巢肿块分别为10cm及8cm；双肺、胰腺、胃未见特殊。患者无恶性肿瘤病史。
行前腹壁肿块粗针穿刺活检。
三条组织呈良性纤维脂肪组织。仅1条组织见局灶上皮被覆。
如图片所示：
请给出如下所述。
1 您对该活检的分析及诊断
2 如果需特殊染色，请列出那些特殊染色。由于组织有限，仅有3张白片。
点评专家：赵澄泉（113楼 链接：>>点击查看<< ）
获奖名单：雅马哈（1楼 链接：>>点击查看<< ）
标签：卵巢肿块
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本帖最后由 筷子 于 2013-05-09 18:28:41 编辑
×参考诊断
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本帖最后由 abin 于 2012-11-24 00:27:38 编辑
Sorry to delay for so long time.
A lot of pepole above have excellent explanation and discussion for this case. Thanks.
I have mentioned and discussed our diagnosis for the first core biopsy and frozen result of second biopsy before.
（抱歉延期。
很多人对本例提供了很好的分析和讨论，谢谢。
我在前面已经提到并讨论过第一次粗针穿刺活检和冰冻诊断。）
腹壁结节活检：转移性腺癌能确定。关键是原发灶的问题也是此例讨论[***]的的问题。此例中有两个免疫组化抗体让人头疼---CDX-2及SMAD4/DPC4，尤其SMAD4这个抗体，SMAD4在卵巢上皮良性肿瘤、卵巢上皮交界性肿瘤、卵巢上皮癌组织中阳性表达率分别为70.8%、81.8%、81.3%；SMAD4抑癌基因的失活是近几年来在胰腺癌方面的一个研究热点，大约35%的患者表现为纯合性缺失，20%的患者表面为杂合性缺失，因此在本病患者中55%存在SMAD4基因的缺失。结合上面特点表明：任何抗体染色没有100%的特异性及敏感性。
再结合下面：人们认为双侧性粘液癌和单侧小于10cm的病灶是转移性的，而大于10cm的单侧病灶是原发的。这种方法能将90％的粘液癌正确分类。后续研究对这一方法进行了证实和改进，精确度仍为90%，且后续研究指出13cm的切除范围要比10cm更好！
结合上面此例最终纠结在：腹壁结节转移性腺癌是卵巢原发转移过来的那？还是腹壁结节和双侧卵巢肿瘤均有其他部位肿瘤转移过来的那？回到临床病史：Regular
CT examination showed bilateral ovarian masse measuring 10 and 8 cm,
respectively; lung negative, pancrease, gastric negative findings also. Patient
has no previous malignant history.下消化道不知检查了否？胰腺需要重点除外，建议MR进一步检查。有些极少数恶性肿瘤以转移为首发症状？
诊断：（腹壁结节活检）转移性腺癌，结合免疫组化结果能除外乳腺、双侧肺及甲状腺恶性肿瘤的转移；建议临床进一步查胰腺及下消化道。如临床除外后考虑卵巢粘液性腺癌转移。免疫组化结果示：TTF-1（-），calretinin（-），CK7（3+），CK20（-），ER/PR（-），PAX8（-），CDX-2（-），SMAD4（-）。
（备注：①有些极少数恶性肿瘤以转移为首发症状；需要临床行胰腺MR及结肠镜检查；②任何抗体染色没有100%的特异性及敏感性，诊断存在一定的难度，需要结合临床，如果双侧卵巢肿瘤符合手术指证，建议切除。）
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本帖最后由 cqzhao 于 2012-12-21 11:22:22 编辑
Now I report you how I signed the case finally. My report is just for your reference.
（现在提供我是如何签发最终报告的，仅供参考。
Final diagnosis: 最终诊断：
Anterior abdominal wall, biopsy- 前腹壁活检-
Metastatic adenocarcinoma. 转移性腺癌。
Comment:评注：
This is a challenge case. The biopsy specimen shows malignant glands infiltrating the dense stroma with obvious desmoplastic reaction. The glands demonstrate irregular shape and the tumor cells with some mucinous features. Multiple immunostains were performed. The metastatic tumor cells are positive for CK7, BerEP4, and negative for CK20, CDX2, TTF-1, ER, PR, PAX8, SMAD4(DCP4), mammaglobin, GCDFP, and calretinin. Overall the stain results and cytomorphologic features of the tumor do not support the gyncological (negative for ER, PR, PAX8, SMAD4), colonic (negative for CK20, CDX2, positive for CK7), lung (negative for TTF-1), breast (negative for mammaglobin, GCDFP, ER, PR), mesothelial (positive for BerEP4, negative for calretinin) primaries. The most significant IHC finding is that the tumor cells are completely negative for SMAD4. The tumors in most organs are positive for SMAD4. One study indicated that 61% of the ovarian metastases from pancreaticobiliary tract show loss of SMAD4 expression (Merident, et al. Am J Surg Pathol 2011;35:276-288). Other studies showed that 20-30% colonic carcinomas are negative for SMAD4. Overall I favor that the tumor is a pancreaticobliary tract primary based on the IHC and morphological features, even though other primary cannot be completely excluded. Clinical correlation with imaging is suggested.
I discussed the case with Dr. xxxx xx at 4:00 PM, September 10, 2012
（本例具有挑战性。活检标本显示恶性腺体浸润致密间质伴明显的促纤维性间质反应。腺体呈不规则形状，肿瘤细胞具有部分粘液特征。检测了多种免疫染色。转移性肿瘤呈CK7和BerEP4阳性，而CK20, CDX2, TTF-1, ER, PR, PAX8, SMAD4(DCP4), mammaglobin, GCDFP和calretinin均阴性。总体上，免疫染色结果和细胞形态学特征不支持的原发部位包括妇科（ER, PR, PAX8, SMAD4均阴性）、结肠（ CK20和 CDX2阴性而CK7阳性）、肺（TTF-1阴性）、乳腺（mammaglobin, GCDFP, ER, PR均阴性）或间皮（BerEP4阳性而calretinin阴性）。最有意义的发现是SMAD4完全阴性。大多数器官肿瘤呈SMAD4阳性。一项研究中提出61%来自胰胆管的卵巢转移癌为SMAD4阴性。其他研究显示20-30%结肠癌呈SMAD4阴性。根据免疫组化和形态学特征，我总体上倾向于肿瘤是胰胆管原发，但其他原发部位不能完全排除。建议结合临床和影像学考虑。
我与XXX医生在某个时间讨论了本例。）
祝贺雅马哈获胜。向雅马哈学习，感谢Dr.cqzhao提供的好病例。
以前老师强调过，自己在书上也看过，胰胆癌转移至卵巢时分化极好，甚至可能误以为卵巢交界性肿瘤，自己却没有深入领会。看来我不是一个好学生，呵呵。
曾几何时，我连宫颈原位腺癌都不认识。后来坚持在华夏网上多看病例，多参与讨论，多翻书查阅文献，学到很多有用知识，那是在书本上和实际工作中都难以获取或者无法体会的。通过本例的学习和讨论，我应该能熟练地应付卵巢粘液性肿瘤的鉴别诊断了。
真诚希望初学者们积极参加讨论，勇于发表自己的观点。
华夏病理/粉蓝医疗
为基层医院病理科提供全面解决方案，
努力让人人享有便捷准确可靠的病理诊断服务。
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本帖最后由 abin 于 2012-11-24 00:42:52 编辑
Before I signed out the case, I had a long discussion with the gynecologist. Two days late, the gynecologist sent me an email to show the thanks for my analysis for the case.
The patient had an intensive CT scan for the abdoman and a 2 cm mass was identified in the pancrease. So most likely the pancrease is the primary site of the tumor with extensive metastasis.
（在签发报告之前，我也妇科医生进行了长时间讨论。两天后，妇科医生发邮件给我表示感谢。
患者做了腹部增强CT，发现胰腺2cm肿块。因此很可能胰腺是原发部位，伴广泛转移）
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本帖最后由 abin 于 2012-11-24 00:44:38 编辑
引用 92 楼 96298 在 2012-10-14 09:56:29 的发言:
本帖最后由 96298 于 2012-10-21 22:52:46 编辑
最终诊断：腹壁结节转移性管状腺癌，结合HE形态及免疫组化结果提示来源于胰腺可能，建议临床进一步检查。（虽然CT检查示双侧附件巨大肿块，大小分别约为10cm和8cm，肺、胰腺、胃均无异常发现，患者无恶性肿瘤病史。）
1.形态：在纤维组织增生性间质中，管状/导管样腺体浸润，这种形态常见来源：胃肠道、肺、乳腺、胰腺、胆管、及卵巢或宫颈腺癌等。
2.临床：双侧卵巢肿物（大小分别约为10cm和8cm）、粘液腺癌样首先考虑转移（非卵巢原发）。
3.IHC：CK7+，CK20-/+，ER-PR-，PAX8-，CDX2-，SMAD4—：
理由：在CK7+和CK20-/+的肿瘤谱中，TTF-1阴性排除肺，calretinin阴性排除间皮（实际上形态也不像），ER-PR-排除乳腺癌，CDX2进一步排除结直肠。SMAD4为抑癌基因，本例为阴性（注意腺腔内核阳性可能非上皮细胞），要知道其在55%胰腺癌中失活，在其他癌如胃肠道、乳腺等也可失活，而在卵巢粘液性腺癌一般会有表达，假设结节是卵巢来的，SMAD4-提示胰腺可能。PAX8表达于大多数苗勒肿瘤等（见赵老师提供的文献，不说了）。
一个悲催的现实：一些卵巢转移的粘液腺癌被诊断原发粘液癌。标准，方法该如何？
I would like to mention that 96298 was the first one to have reasonable and correct diagnosis and interpretation for this case.
（我也注意到96298是第一位得出合理、正确诊断和解释者）
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本帖最后由 abin 于 2012-11-24 00:45:45 编辑
In addition I would like to thank all people who read or participated the discussion for this case, especially Abin who spent a lot of time to analyze the case and show many useful references.
（另外感谢所有浏览过或参加讨论的人，特别是abin花费了大量时间分析并提供了许多有用的参考资料）
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本帖最后由 abin 于 2012-11-24 00:51:30 编辑
Another reference
Am J Surg Pathol. 2011 Feb;35(2):276-88.
Ovarian metastases of pancreaticobiliary tract adenocarcinomas: analysis of 35 cases, with emphasis on the ability of metastases to simulate primary ovarian mucinous tumors.
Source
Departments of Pathology, The Johns Hopkins University School of Medicine and Hospital, Baltimore, MD 21231, USA.
Abstract
Metastatic mucinous carcinomas in the ovary are readily recognized when they show characteristic features, including bilateral involvement, only moderate tumor size, surface and superficial cortical involvement, nodular growth, and an infiltrative pattern. However, it is well established that some metastatic mucinous carcinomas can simulate primary ovarian mucinous tumors grossly and microscopically. Metastatic pancreaticobiliary tract adenocarcinomas present a particular diagnostic challenge due to their ability to exhibit borderline-like and cystadenomatous growth patterns, which can be misinterpreted as underlying primary ovarian precursor tumors and can be erroneously used to support interpretation of the carcinomatous components as arising from these purported precursors within the ovary. Thirty-five cases of metastatic pancreaticobiliary tract adenocarcinomas were analyzed. The mean patient age was 58 years (median, 59 y; range, 33 to 78 y). In 15 cases (43%), the pancreaticobiliary tract and ovarian tumors presented synchronously and in 2 cases (6%) the ovarian tumors presented earlier as the first manifestation of the disease. Ovarian tumors were bilateral in 31 cases (89%). Mean and median tumor sizes were 10.6 and 9.5 cm, respectively (range, 2.5 to 21.0 cm). Nodularity was present in 22 cases (63%) and surface involvement was identified in 14 cases (40%). An infiltrative growth pattern was present at least focally in 28 cases (80%), accompanied by borderline-like and/or cystadenomatous areas in 17 (49%) cases and as the exclusive pattern in 11 cases (31%). Conversely, borderline-like and cystadenomatous patterns were identified in 24 cases (69%) and as the exclusive patterns (either pure or combined with one another) in 7 cases (20%). Dpc4 expression was lost in 20 of 33 tumors analyzed (61%). Of 25 patients with follow-up, 23 patients had died of disease (mean/median time, 9/6 mo; range, 1 to 39) and 2 patients were alive with disease (at 1 and 25 mo). Frequent bilateral ovarian involvement, moderate tumor size, nodularity, and infiltrative patterns are useful features for identifying these ovarian tumors as metastatic. However, many tumors exhibit borderline-like and cystadenomatous patterns that, when dominant and combined with synchronous presentation, make recognition as metastases an ongoing challenge. Loss of Dpc4 expression provides the most useful immunohistochemical evidence for establishing the pancreaticobiliary tract as the most likely source of these metastatic mucinous carcinomas in the ovary.（卵巢转移性粘液癌中确定胰胆管是最可能起源部位的最有用的免疫组化证据是Dpc4阴性）
引用 92 楼 96298 在 2012-10-14 09:56:29 的发言:
本帖最后由 96298 于 2012-10-15 22:48:49 编辑
最终诊断：腹壁结节转移性管状腺癌，结合HE形态及免疫组化结果符合来源于胰腺转移，建议临床再查查。--怎么会有这个结论？（虽然CT检查示双侧附件巨大肿块，大小分别约为10cm和8cm，肺、胰腺、胃均无异常发现，患者无恶性肿瘤病史。）
1.形态：在纤维组织增生性间质中，管状/导管样腺体浸润，这种形态常见来源：胃肠道、肺、乳腺、胰腺、胆管、及卵巢或宫颈腺癌等。
2.临床：双侧卵巢肿物（大小分别约为10cm和8cm）、粘液腺癌样首先考虑转移（非卵巢原发）。
3.IHC：CK7+，CK20-/+，ER-PR-，PAX8-，CDX2-，SMAD4—：
理由：在CK7+和CK20-/+的肿瘤谱中，TTF-1阴性排除肺，calretinin阴性排除间皮（实际上形态也不像），ER-PR-排除乳腺癌，CDX2进一步排除结直肠。SMAD4为抑癌基因，本例为阴性（注意腺腔内核阳性可能非上皮细胞），要知道其在55%胰腺癌中失活，在其他癌如胃肠道、乳腺等也可失活，而在卵巢粘液性腺癌一般会有表达，假设结节是卵巢来的，SMAD4-提示胰腺可能。PAX8表达于大多数苗勒肿瘤等（见赵老师提供的文献，不说了）。
一个悲催的现实：一些卵巢转移的粘液腺癌被诊断原发粘液癌。标准，方法该如何？
What percentage of colonic cancer cases are SMAD4 negative?
学习了96298在94楼提供的非常有用的文献摘要，翻译如下：
卵巢转移性粘液癌与卵巢原发性粘液肿瘤（不典型增生性/交界性和癌）的区分可能很难，因为形态学相似。我们评估57例卵巢原发性粘液肿瘤（不典型增生性41例和癌16例）和46例卵巢转移性粘液癌的CK7、CK20和 Dpc4（核转录因子，胰腺癌55%失活）和MUC5AC（胃粘蛋白基因）。卵巢原发性粘液癌几乎总是CK7弥漫阳性(98%)、Dpc4弥漫阳性(100%)和 MUC5AC弥漫阳性 (98%)，而CK20局灶性弥漫阳性(68%)。
结直肠粘液癌CK20弥漫阳性(100%)和Dpc4弥漫阳性(89%)，通过阳性率不同与原发性卵巢癌区别，因为通常不表达CK7和MUC5AC(每种抗体均为67%阴性）。原发性卵巢癌和转移性结直肠癌或阑尾癌具有相同的CK7和CK20表达谱，通常可以用阳性表达模式不同而区分（卵巢肿瘤弥漫性CK7阳性而斑片状CK20阳性，但结直肠癌和阑尾癌斑片状CK7阳性而弥漫性CK20阳性）。胰腺癌与原发性卵巢癌具有相同的表达模式：弥漫性CK7阳性、弥漫性MUC5AC阳性 (92%)、局灶到弥漫性CK20阳性(71%)。但Dpc4阴性率46%。不表达Dpc4有助于区分卵巢转移性胰腺癌、原发性卵巢粘液性肿瘤和其他部位转移性粘液癌。
所以，重新考虑，本例胰腺癌转移至腹壁的可能性最大。推测卵巢肿瘤也是如此。
谢谢96298！
华夏病理/粉蓝医疗
为基层医院病理科提供全面解决方案，
努力让人人享有便捷准确可靠的病理诊断服务。
SMAD4, also termed DPC4,2 was originally isolated from human chromosome 18q21.1 as a tumor suppressor gene for pancreatic cancer
SMAD4又称DPC4，最初从人染色体18q21.1分离，是胰腺癌的肿瘤抑制基因
A lack of reactivity for Dpc4 suggests a pancreatic primary, since almost half of pancreatic adenocarcinomas show loss of this marker, whereas ovarian mucinous tumors express it [57].
不表达Dpc4支持胰腺原发，因为大约一半胰腺癌不表达，而卵巢粘液性肿瘤表达[57]
参考文献[57]就是上述96298提供的文献摘要。
华夏病理/粉蓝医疗
为基层医院病理科提供全面解决方案，
努力让人人享有便捷准确可靠的病理诊断服务。
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本帖最后由 abin 于 2012-11-06 21:32:29 编辑
以下来自我们正在翻译很快就要出版的Blaustein’s Pathology of the Female Genital Tract， 6 Edition
许多特征有助于区分卵巢原发性粘液性肿瘤与转移性胰腺粘液性肿瘤以及其他部位原发的粘液性癌。双侧卵巢肿瘤强烈支持转移性。卵巢表面和卵巢皮质浅层发现促纤维增生性间质中的种植性癌有助于转移的诊断。临床表现往往很有帮助，对于双侧卵巢存在粘液性癌的病例，常常出现腹腔内扩散最符合卵巢癌是继发性累及。上文所述镜下出现异质性图像也有助于诊断转移癌。再请读者参考表18.1，我们最近在其中增加了所谓的粘液样肉芽肿[68]，我们认为与转移性粘液性肿瘤相比，粘液样肉芽肿在原发性肿瘤中明显更为常见。
免疫组织化学在区分转移性胰腺癌和原发性卵巢粘液性肿瘤时的作用有限。二者通常都有CK7+和不同程度的CK20+（图18.68）[91]。不表达Dpc4提示胰腺原发，因为将近一半的胰腺癌不表达Dpc4，而卵巢粘液性肿瘤表达Dpc4[57]。然而，Dpc4阳性显然没有鉴别价值。
57. Ji H, Isacson C, Seidman JD, Kurman RJ, Ronnett BM (2002) Cytokeratins 7 and 20, Dpc4, and MUC5AC in the distinction of metastatic mucinous carcinomas in the ovary from primary ovarian mucinous tumors: Dpc4 assists in identifying metastatic pancreatic carcinomas. Int J Gynecol Pathol 21:391–400
华夏病理/粉蓝医疗
为基层医院病理科提供全面解决方案，
努力让人人享有便捷准确可靠的病理诊断服务。
