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1、乳腺肿瘤,一位84的老太太由于乳腺结节做了乳腺切除及腋窝淋巴结清扫，大体检查有2个结节，一个5x3.5，另一个直径2cm。 An 84 year old woman had a total mastectomy with axillary dissection for a breast nodule. The main mass was 5 x 3.5 cm, and a 2 cm mass was nearby.,What is your diagnosis?,伴有导管原位癌成份的浸润性分泌性癌Invasive apocrine carcinoma with an in situ compo
2、nent,浸润性分泌性癌在乳腺癌中是一个不太常见的类型，约占所有乳腺癌的1-4%，在老年妇女中比浸润性导管癌更为常见。通常显示一个囊内结节，镜下，肿瘤由界限较清的细胞组成，具有颗粒状嗜伊红的细胞质，多具有泡状细胞核和明显的核仁和可以见到的猪嘴样的腺体，这种诊断仅限于具有明显顶浆分泌改变和明显恶性的肿瘤中。,Invasive apocrine carcinoma is an uncommon subtype of breast carcinoma, representing 1-4% of all carcinomas. It typically affects older women than
3、 infiltrating ductal carcinoma (Breast Cancer 2002;9:43). Grossly, it may present as a mural nodule within a cyst. Microscopically, the tumors are composed of cells with distinct cell margins, eosinophilic cytoplasm and granules. They have vesicular nuclei with prominent nucleoli, and may have gland
4、s with apocrine snouts. This diagnosis should be limited to tumors with widespread apocrine change and obvious malignancy.,Case of the Week #62,一位22岁的女性伴有逐渐增大的右侧乳腺结节，2 个月病史，无乳头溢液，本人否认曾用过激素或其它药物，肿块外观无炎症改变，切除肿块重540克， 14 x 11 x 4 cm, 实性，卵圆形，边界较清，切面白色，质较硬，散在裂隙样改变， A 22 year old Caucasian woman had a two
5、-month history of an enlarging right breast mass. There was no nipple discharge and she denied use of hormones or other drugs. The mass was tender to palpation without any external signs of inflammation. The resected specimen was 540 grams, 14 x 11 x 4 cm, solid, ovoid and well-circumscribed. The cu
6、t surface was white, firm and homogenous with a few scattered slit-like spaces (Figures 1, 2). Low and medium power showed large hyperplastic lobules with a proliferation of ductules and acini. Few ducts were dilated (Figure 3, 4, 5). The enlarged lobules were strongly immunoreactive for cytokeratin
7、 8 (Figure 6).,中低倍观察可见到较大的扩张的小叶伴有小叶内腺管和核的增生，几乎没有导管扩张，扩张小叶组化CK8阳性。,硬化似乎开始于小叶的中央并向周围放射，腺泡周围纤维化明显，马氏三色染色可见小叶内纤维化，The sclerosis seemed to start at the center of the lobule and radiate towards the periphery, incarcerating the acini with severe fibrosis and atrophy (Figure 7, 8). The Trichrome stain highl
8、ighted dense interlobular fibrosis and a peculiar periacinar sclerosis with a glomeruloid pattern (Figure 9, 10). The myoepithelial cells were prominent in these areas, as demonstrated by Calponin immunoreactivity (Figure 11),What is your diagnosis?,乳腺硬化性小叶增生Sclerosing lobular hyperplasia of the bre
9、ast,硬化性小叶增生是一个不太常见的病变，多表现为小叶显蓍增生和小叶内间质的弥漫性纤维化，几乎均发生于年青女性，病人通常短期内可发生一个无痛性的边界较清的包块，此类病变首先被KOYI报道了18例，多发生于28-32的年龄。,Sclerosing lobular hyperplasia is an uncommon lesion of the female breast characterized by prominent hyperplasia of the lobules with severe and extensive fibrosis of the intralobular stro
10、ma, and to a lesser degree, the interlobular parenchyma. It occurs almost exclusively in young women. Patients generally complain of a palpable, painless or slightly tender and well-defined lump in the breast of short duration. This lesion was first reported by Kovi et al (1) who described it in a g
11、roup of 18 patients, mainly young women. It is possible that Cheatle (2) in 1922 was referring to the same lesion. The mean age of patients is 28 to 32 years, with a range of 12 to 46 years (3).,在最初的文章中此类病变多被描述为伴有增生小叶的纤维性肿瘤，另一些作者认为是乳腺腺病， 临床鉴别诊断包括青少年巨大纤维腺瘤或青少年乳腺发育，和叶状囊肉瘤，但这些病变均没有小叶的硬化。 病理上，切除标本从小的卵圆形
12、的1cm实体性肿瘤到大的实体性肿瘤均可见到，FNAC无特异性改变并与乳腺纤维性肿瘤有重叠，包括平铺的片状卵圆形的导管上皮细胞呈腺泡样排列，在干净的背景下散在裸核细胞和不定数目的基质碎片。硬化性小叶性增生的自然病程不清，但没有恶性或切除后复发的报道,Its relation to fibroadenoma or fibroadenomatoid changes around the hyperplastic lobules was noted in the original article, and some authors have redefined this lesion as fibro
13、adenomatosis, fibroadenoid mastopathy, or fibroadenomatoid hyperplasia (1, 4). In our case, this feature is not present. The clinical differential diagnosis includes giant juvenile fibroadenoma and juvenile hypertrophy in younger patients, and phyllodes tumor in older patients. None of these lesions
14、 have been associated with lobular sclerosis. Pathologically, the resected specimens vary from small ovoid and white solid tumors of 1 cm up to large solid tumors. Fine needle aspiration findings are nonspecific and overlap with fibroadenoma, including flat sheets of oval ductal epithelial cells in
15、an acinar arrangement, a few bare nuclei in a clean background and variable stromal fragments (5, 6). The natural course of sclerosing lobular hyperplasia is not known. However, no association with malignancy or recurrence has been documented.,Case of the Week #45,Clinical history 一位72的女性病人由于X线发现钙化行
16、乳腺切除术，过去史无异常A 72 year old woman with no prior history underwent a lumpectomy for calcifications on her mammogram,What is your diagnosis?,伴有神经内分泌分化的低级别导管内癌Low grade DCIS with neuroendocrine features,免疫组化Syn证实肿瘤细胞伴有神经内分泌分化 An immunostain for synaptophysin confirmed the neuroendocrine nature of the tum
17、or cells (image9, image10,神经内分泌型导管内癌较少见，它亦被称做管内型乳头状癌。它特征性的出现于60岁或以上的老年妇女，总伴有乳腺肿块或乳头溢液，它通常与伴有派杰氏病样的导管内乳头状瘤一起出现，尽管是一个低级别肿瘤，但也可伴有浸润性成分，浸润性成分多可见粘液或神经内分泌特征。,Neuroendocrine-type DCIS is a rare variant, that is also called intraductal papillary carcinoma. It typically occurs in women age 60 years or greate
18、r, and is often accompanied by a breast mass or nipple discharge. It is frequently associated with intraductal papilloma with pagetoid involvement by the tumor cells, and despite its low grade nature, may have an invasive component, which often has mucinous or endocrine features,显微镜下，肿瘤呈实性生长，或可见菊形团样
19、改变，细胞呈多角形，卵圆形或细长型，具有温和和、卵圆形的细胞核，也可伴有胞质内嗜碱性粘液聚集，间质纤维多少不定但通常常没有坏死。 细胞学涂片显示单一的浆细胞样细胞和乳头状分叉样结构。,Microscopically, the tumor has a solid growth pattern, or may have neuroendocrine-like festoons and rosettes and a prominent fibrovascular septa. The cells are polygonal, oval or spindled, with abundant granu
20、lar eosinophilic cytoplasm and bland, oval nuclei. There may be accumulation of basophilic intracellular mucin. Stromal fibrosis is variable. There is usually no necrosis. Cytologic smears show plasmacytoid tumor cells and arborizing papillary fronds,Case of the Week #37,临床病史Clinical history 一位49岁的中
21、年妇女因以前组织学诊断为乳腺低级别导管原位癌而行乳腺肿块的针吸活检，穿出9mm病变，但并没有多灶性DCIS的改变，上皮显示了典型的纤维性肿瘤特点，但存在一些不典型细胞，没发现核分裂像。,A 49 year old healthy woman underwent needle localization excision of a breast mass for biopsy proven low grade ductal carcinoma in situ. A 9 mm lesion was identified histologically adjacent to, but not invo
22、lved by, multifocal DCIS. The epithelial component in the nodule showed the typical cytoarchitecture of fibroadenoma, but also had some atypical cells. No mitotic figures were found.,What is your diagnosis?,伴有奇异型间质巨细胞的纤维腺瘤(对于此标本的这部分区域) Fibroadenoma with bizarre stromal giant cells (for this portion
23、of the specimen),显微镜下显示间质细胞显著增大，核染色较深伴有多形性核，很多间质细胞内可见核内假包含体，同时乳腺亦显示了小灶性低级别DCIS的特点，也包含在了此病变的诊断中。,The microscopic images show stromal cells with markedly enlarged and hyperchromatic, pleomorphic nuclei. Many of the stromal cells showed multinucleated forms or prominent round, intranuclear pseudoinclus
24、ions. The remaining breast showed foci of DCIS with low grade nuclear features, which of course was included within the final diagnosis.,组织学特点往往是区分良恶性实体性病变的可靠指标，明显增大的多形性的核通常被视为恶性的特点，但偶尔此类病变会存在于明显良性的肿瘤中，这种核呈恶性样改变但病变呈良性的形态有时在多形性子宫平滑肌 瘤中会遇到(称为退行性改变)。退行性型异型还可在以下病变中见到，如成骨性肿瘤，软骨粘液纤维瘤，肾嗜酸细胞肿瘤，间质增生的前列腺癌，子宫内
25、膜息肉，唾液腺腺瘤多形性腺瘤（ 1-4 ） ，以及在内分泌肿瘤。在乳腺纤维腺瘤中类似的核的变化很少看到。,Well-defined histological parameters typically are reliable indicators to differentiate benign from malignant entities. The presence of enlarged and pleomorphic nuclei is classically regarded as a feature of malignancy, but may on occasion be evid
26、ent in lesions with completely benign behavior. This discordance between nuclear atypia and behavior is characteristically encountered in uterine leiomyomas (referred to as “symplastic” change), or schwannomas (described as “ancient change”). Degenerative type atypia has also been described in osteo
27、blastoma, chondromyxoid fibroma, fibrodysplasia, renal oncocytoma, stromal hyperplasia of the prostate, endometrial polyps, and salivary polymorphic adenoma (1-4), as well as in endocrine neoplasms. Similar nuclear changes arising in mammary fibroadenomas are only seen rarely.,组织学结构上，伴有奇异巨大间质细胞的纤维腺瘤
28、通常如此例所见，这种奇异的巨间质细胞通常具有细胞质，没有核分裂像，在乳腺病变中其它具有非典型性间质细胞的病变包括叶状肿瘤、肉瘤、化生性乳腺癌，鉴别诊断中包括缺乏基质的过度生长，细胞拥挤重叠和核分裂像，最重要的是，细胞核呈“粉尘”样改变。当多核的巨细胞出现核分裂，坏死，基质过度生长或其它的明显病变时，通常要考虑叶状肿瘤,Architecturally, the overall pattern of fibroadenoma with bizarre stromal giant cells is that of the usual fibroadenoma, but with diffuse st
29、riking nucleomegaly of the stromal cells, accompanied by adequate cytoplasm. Mitotic figures are notably absent. Other neoplastic lesions in the breast that show atypical stromal cells include phyllodes tumor, sarcoma, and metaplastic breast carcinoma. Distinction from these other lesions can be mad
30、e by recognition of the lack of stromal overgrowth, cellular crowding and mitotic figures, and most importantly, the lack of crisp nuclear details (i.e. the chromatin is “smudgy”). The presence of multinucleated giant cells in combination with mitotic activity, necrosis, stromal overgrowth or hyperc
31、ellularity raises the question of another lesion, usually phyllodes tumor (5). The degree of atypia in fibroadenoma with bizarre stromal giant cells actually exceeds that which typifies malignant processes in the breast, another diagnostic clue.,伴有丰富细胞质的奇异性核的改变亦可见于放射治疗后，由于射线可抑制核分裂，细胞核变得很大，甚至可见核内假包含体
32、，与放射引起的不同，伴有奇异巨细胞核的纤维腺瘤不伴有上皮和间质的异常，非典型性仅仅见于局灶性区域，且没有放射病史。,Bizarre nuclear alteration in the presence of abundant cytoplasm may also be seen following external beam radiation therapy. Due to radiation-induced inhibition of cell division, the nucleus becomes enlarged, acquiring bizarre features includ
33、ing pseudoinclusions. Unlike radiation effect, fibroadenoma with bizarre stromal giant cells shows no epithelial or vascular abnormalities, the atypia is well-localized, and there is no history of radiation exposure.,伴有奇异基质细胞的纤维腺瘤是一个不太常见的乳腺病变，很易于与叶状囊肉瘤等其它恶性变病相混淆，尤其在FNAC中，这种奇异核的改变与基质的退行性变有关，它们并不代表侵略性
34、或恶性改变，治疗以保守切除为主。,Fibroadenoma with bizarre stromal cells is an uncommon benign entity in the breast which can be easily confused with phyllodes tumor or other lesions with malignant stromal cells, particularly in fine needle aspirations (6). The bizarre nuclear changes are related to degenerative al
35、terations, and they do not indicate aggressive or malignant behavior. Treatment is conservative local excision, which is completely curative.,Case of the Week #35,Clinical History 一位54岁妇女左乳腺外上限有一个较大的肿块伴有乳头间断性溢液，皮肤及腋窝检查均阴性,她姐姐55岁患乳腺癌。切除送检。,A 54 year old woman presented with a large palpable left brea
36、st mass in the upper outer quadrant and mild intermittent nipple discharge. Examination was negative for overlying skin changes or axillary nodal enlargement. Her older sister had breast cancer at age 55. An excisional biopsy was performed,大小不一的囊性扩张性病变，其内包含似甲状腺滤泡内胶质样的嗜伊红物质。 Multiple variably sized c
37、ysts, containing an eosinophilic homogeneous secretion similar to colloid in thyroid gland follicles,大多数囊腔周围覆扁平的似良性的上皮，伴有腔内浓稠的基质。Many of the cysts are lined by benign-looking flattened epithelium, with dense intervening intracystic stroma,镜下可见腔内分泌物显示与周围扇形排列的上皮有分隔 The intraluminal secretions show cha
38、racteristic microscopic artifacts - fine, parallel cracks and shrinkage of the cyst content with peripheral scalloping,其它囊腔内可见多层乳头状上皮细胞，核无明显异型性 Other cysts were lined by multilayered micropapillary intracystic proliferations composed of atypical ductal epithelial cells with highly pleomorphic nucle,
39、What is your diagnosis?,囊性高分泌性导管内癌 Cystic hypersecretory ductal carcinoma in situ,1984年， Rosen and Scott 描述了一类特殊的，较少见的管内型乳腺癌，称做囊性分泌性导管癌，至今，仅有40余例囊性分泌性癌被报道，且大多为个案报道。大多数的此类病变都是管内型癌。但是，良性增生性病变，被称做管内型分泌性增生，也曾被报道过。一些导管分泌性癌可见到确切的上皮浸润到间质去，转移到腋窝淋巴结的也有报道。 In 1984 Rosen and Scott described a distinctive, rare
40、 form of intraductal carcinoma of the breast, which they called cystic hypersecretory duct carcinoma (1). To date, less than 40 cases of cystic hypersecretory lesions have been described, mostly as case reports. Most of these lesions are intraductal carcinomas; however, benign proliferative lesions,
41、 called cystic hypersecretory hyperplasia, have also been described. Some cases of hypersecretory duct carcinoma demonstrate invasive areas of frankly malignant epithelial cells into the stroma (2-4). Metastases to axillary lymph node have also been reported,囊性高分泌性癌的临床表现或乳腺X线摄片无特殊性。它们由可触及的明显结节组成，偶尔会
42、有乳头间断性溢液，乳腺X线摄片不均匀的密度值或 偶见和微小钙化偶尔可见到,The clinical manifestations or mammographic features of cystic hypersecretory lesions are non-specific. They consist of a palpable breast mass and occasionally nipple discharge. There is a mammographic asymmetric density, with occasional microcalcifications.,通常，乳
43、腺囊性高分泌性癌和增生无法区分，它们类似于青少年多发性乳头状瘤，通常由较大的边界不太清楚的较韧的结节组成。纤维组织内可见多个小囊泡状物。诊断线索是囊泡内可见丰富的粘稠的液体。Grossly, cystic hypersecretory hyperplasia and carcinoma are indistinguishable and they resemble juvenile papillomatosis of the breast. There is a large, ill-defined firm to rubbery spongy mass of fibrous tissue c
44、ontaining multiple small cysts. One diagnostic hint is the presence of abundant thick, sticky mucin within the cysts,囊性高分泌性病变完全由不同大小的囊泡样结构组成，一些相当大且呈螺旋状，囊内呈胶状物，腔内物边缘凝集且收缩，可能是由于标本处理所致。囊内壁衬覆上皮从较低平的温和的上皮到成簇的微小乳头状的增殖不等，而后面的病变形态可提示导管原位癌，当没见到后面这些形态时，可诊断囊内高分泌性增生，这些病变必须广泛取材以排除浸润性成分。,Cystic hypersecretory les
45、ions are composed entirely of cystic structures of various sizes, some quite large and convoluted. The cystic material resembles colloid, often with parallel fracture lines, a retraction halo around the intraluminal contents, and overlapping due to processing. The cyst wall lining varies from a blan
46、d, attenuated low cuboidal, simple epithelium to a highly tufted, micropapillary proliferation. These latter areas warrant a diagnosis of ductal carcinoma in situ. In their absence, a diagnosis of cystic hypersecretory hyperplasia is rendered. These lesions should be generously sampled to exclude th
47、e presence of an invasive component,组织学鉴别诊断包括良性管内柱状病变、青少年多发性乳头状纤维腺瘤、假性粘液囊肿、粘液腺癌、分泌性癌、哺乳期乳腺增生、但镜下改变足可以与以上区分。,The histological differential diagnosis includes benign intraductal proliferative lesions, juvenile papillomatosis, mucocele-like lesions, mucinous cystadenocarcinoma, columnar cell lesions, s
48、ecretory carcinoma, and pregnancy-like hyperplasia. However, the microscopic features on excision are invariably specific enough to avoid misinterpretation.,囊性高分泌性导管癌在FNA中无法诊断，囊性外观和温和的细胞形态总会造成纤维囊性改变的假阴性诊断。大多数的FNA在此类病变中的诊断不是阴性的就是提示恶性的，没有确切的指标来诊断，如果在FNA中见到丰富的甲状腺胶质样物同时伴有细胞的非典型性，此诊断可以考虑。,Cystic hypersec
49、retory ductal carcinoma of the breast represents a diagnostic pitfall on fine needle aspiration (FNA). The multicystic appearance and often bland cytological features can cause a false-negative diagnosis of fibrocystic changes. Most reported FNA cytology cases are either negative or reveal cells suggestive of malignancy, without the possibility of establishing a specific diagnosis (3, 4). If abundant thyroid colloid-like secretions accompanying atypical cells are aspirated, this diagnosis can be considered.,总结：乳腺囊性高分泌性导管癌在乳腺管内癌中是一个较少见的类型，具有低级别的特点，但具有潜在性浸润和转移，应和乳腺其它病变相区分，重视细胞学检查，并对乳腺