Fine-needle aspiration biopsy of invasive micropapillary carcinoma of the breast: a report of five cases

Invasive micropapillary carcinoma of the breast is an uncommon variant of infiltrating ductal carcinoma. Observing its distinctive cytologic appearance and aggressive behavior is important for early diagnosis by fine-needle aspiration cytology (FNAC). There are only a few reported cases in the literature. Five women presented with breast masses. FNAC showed malignant epithelial tumors, and mastectomy materials showed invasive micropapillary carcinoma for all of them. Three patients had axillary lymph node metastases. Invasive micropapillary carcinoma, with its angulated papillary clusters lacking a fibrovascular core, and irregular crowded nuclei, has a distinctive cytologic appearance which correlates with its histological features. A differential diagnosis from other primary or metastatic papillary lesions of the breast may be possible using immunohistochemistry and some cytologic features. The limited experience with invasive micropapillary carcinoma should not discourage others from undertaking further studies.     

Primary invasive micropapillary carcinoma of the stomach

Reported herein is the case of a 74-year-old man with an unusual gastric carcinoma that developed at the lesser curvature of the stomach. The tumor consisted of small clusters of carcinoma cells surrounded by clear spaces, with histopathology similar to invasive micropapillary carcinoma (IMPC) of the breast. The carcinoma cells, which had downregulation of E-cadherin expression, invaded the subserous tissue and metastasized to the perigastric lymph nodes. IMPC, an unusual subtype of invasive breast carcinoma, is known to have frequent lymph node metastases, resulting in a poor clinical outcome. Although IMPC has been reported in breast, urinary bladder, ureter, lung, salivary gland and colon, to the best of the authors' knowledge this is the first report of IMPC arising in the stomach. Presented here are the clinicopathological features of primary IMPC of the stomach.     

Micropapillary carcinoma of the urinary bladder: report of a case and review of its cytologic features

Micropapillary carcinoma (MPC) is an aggressive variant of urothelial carcinoma. MPC has a propensity to invade lymphovascular spaces and detrusor muscle early in the disease that often leads to upstaging and/or lymph node metastasis in many cases at cystectomy. Its association with the usual high-grade urothelial carcinoma provides an easy recognition of malignancy in cytology specimens without attempt at separating or identifying the MPC component. This may be related to our limited familiarity of its cytologic features with only 4 cases described in the literature. We report another case of MPC and highlight its features in cytologic preparations including the presence of singly scattered tumor cells with high nuclear to cytoplasmic ratio and pleomorphic nuclei, clustered cells devoid of fibrovascular core (micropapillae), 3-dimensional cell aggregates, cytoplasmic vacuoles, and micropapillae exhibiting some features of low-grade urothelial neoplasm. Appreciation of these features may help facilitate its early diagnosis and hopefully a better outcome for these aggressive tumors.     

The clinicopathological significance of CD44+/CD24-/low and CD24+ tumor cells in invasive micropapillary carcinoma of the breast

Breast cancer cells with a CD44(+)/CD24(-/low) phenotype have been suggested to have tumor-initiating properties. It is unclear whether their presence correlates with clinicopathological features of invasive micropapillary carcinoma (IMPC) of the breast, an unusual subtype of breast cancer with a high incidence of lymph node metastasis and poor prognosis. CD44 and CD24 expression was determined by double-staining immunohistochemistry in 103 cases of IMPC and in 94 cases of invasive ductal carcinoma (IDC). The prevalence of CD44(+)/CD24(-/low) tumor cells was higher in IMPC than in invasive ductal carcinoma IDC (P=0.018). The CD44(+)/CD24(-/low) tumor cells were also detected in adjacent stroma surrounding the micropapillary structure in 53.4% (55/103) of IMPC, but only in 7.4% (7/94) of stroma of IDC. These tumor cells in stroma of IMPC were positive for vimentin and α-smooth muscle actin, and negative for E-cadherin. The CD44(+)/CD24(-/low) tumor cells in the micropapillary structure of IMPC were associated with those in stroma (P=0.000). Moreover, they were both associated with lymphovascular invasion and extranodal extension, respectively (P<0.05). The proportion of CD24(+) tumor cells was also higher in IMPC than in IDC (P=0.035), and the CD24(+) tumor cells were associated with lymph node metastasis in IMPC (P=0.010). The results suggest that the increased proportion of CD44(+)/CD24(-/low) tumor cells and CD24(+) tumor cells and the epithelial mesenchymal transition may play an important role in aggressiveness and high metastatic risk of breast IMPC.     

乳腺浸润性微乳头状癌临床病理因素的研究现状

目的 探讨年龄、肿瘤大小、组织学及核分级、腋淋巴结、激素受体、生长因子受体及细胞增值率等临床病理因素在乳腺浸润性微乳头状癌（IMPC）发生、发展、转移及预后的评估中的意义.方法 应用Pubmed及CNKI数据库系统以“IMPC”为关键词检索文献,筛选出相关一次文献,对文献进行分析.结果 IMPC中肿瘤大小、IMPC成分的比例、共存病灶的病理类型和组织学分级均与淋巴结转移的发生率无关;IMPC独特的形态学特征和间质淋巴细胞浸润可能是其高侵袭性的原因所在;IMPC中雌激素受体（ER）和人类表皮生长因子受体2（HER2）阳性表达比率高,其中,ER阳性表达可作为一个积极预后指标.结论 对IMPC这一特殊亚型认识还比较肤浅,随着研究的不断深入,IMPC的诊治状况将得到进一步的改观.     

乳腺浸润性微乳头状癌上皮性钙黏附素的表达及意义

目的 研究细胞黏附分子,在乳腺浸润性微乳头状癌肿瘤细胞的集团性浸润、转移中的表达和作用。方法 复习2002年1月～2003年5月所有手术切除乳腺癌组织切片,按WHO乳腺癌分类分组,浸润性微乳头状癌(IMPC)64例、浸润性导管癌(IDC)57例。采用免疫组织化学标记的链霉素抗生物素蛋白-生物素(LSAB)法检测64例IMPC中E-钙黏附素的表达,并同IDC加以比较。结果 E-钙黏附素主要表达于IMPC细胞膜;IMPCE-钙黏附素表达率(85．9％,55／64)明显高于IDC(43．9％,25／57),并且在微乳头状肿瘤细胞集团内的细胞间连接面表达正常,而在细胞集团面向间质侧的表达明显减弱或不表达;IMPC组的淋巴结转移率(85．9％,55／64)明显高于IDC(52．6％,30／57)．．其淋巴结阳性、E-钙黏附素阳性病例的d-连接素、B-连接素共同表达率(45．1％,26／51)也明显高于IDC(15．4％,2／13)。结论 IMPC的微乳头状肿瘤细胞集团内细胞间黏附性强、而与间质间的黏附性减弱或消失的特性可能是IMPC具有高转移潜能的原因之一。     

Inconclusive or erroneous fine‐needle aspirates of breast with adequate and representative material: A cytologic/histologic study

Adequately cellular and representative fine‐needle aspirates (FNAs) of breast have a high diagnostic accuracy. There is, however, a recognized category designated as “gray zone” where a definitive diagnosis cannot be reached. We reviewed our experience in this category to identify useful diagnostic parameters. Twenty‐four such FNAs with surgical follow‐up were retrieved from AUBMC files (2003–2009). Cytology slides were reviewed blindly. All cases were females, 29–73 years. There were three erroneous and 21 inconclusive diagnoses. The majority (15) was invasive adenocarcinomas: two cribriform, four tubular, one lobular, and eight not otherwise specified. The remaining cases were papillary and fibroepithelial tumors (three each), ductal carcinoma in situ, cribriform (two), and one adenomyoepithelioma (AME). Useful diagnostic features included: (1) Biphasic cell population with focal nuclear atypia and intranuclear and cytoplasmic vacuolar inclusions (AME). (2) Complex clusters of epithelial cells with cribriform architecture (cribriform carcinoma). (3) Rigid tubular epithelial structures with abrupt change in diameter, ending in pointed tips with abnormal branching (tubular carcinoma). (4) Cellular stromal fragments (fibroepithelial tumors). (5) Papillary fibrovascular cores, columnar cells, and three‐dimensional papillary epithelial fragments (papillary tumors). Myoepithelial cells classically described in benign aspirates were not always a discriminatory factor. The “gray zone” in breast FNA is usually due to overlapping cytologic features of some benign and malignant lesions. Useful distinguishing cytologic features are described. Diagn. Cytopathol 2014;42:405–415. © 2013 Wiley Periodicals, Inc.     

Breast epithelial cells in dermal angiolymphatic spaces: a manifestation of benign mechanical transport

Evidence suggesting that breast epithelial cells may reach axillary lymph nodes by benign mechanical transport (BMT), rather than metastatic means, has been recently reported. We report a case of a patient with ductal carcinoma in situ of the breast, who had displaced epithelial elements in the mastectomy specimen, dermal angiolymphatic spaces, and a sentinel lymph node. We attribute the epithelial aggregates in the dermal angiolymphatic spaces and a single cell in the sentinel lymph node to BMT, based on the clinicopathological findings of the case. We, therefore, suggest that the effects of BMT be considered in the differential diagnosis of epithelial aggregates in dermal angiolymphatic spaces in the appropriate clinicopathological setting.     

Incomplete inside-out growth pattern in invasive breast carcinoma: association with lymph vessel invasion and recurrence-free survival

Invasive micropapillary carcinoma (IMPC) is a rare subtype of epithelial tumor of the breast listed in the 2003 World Health Organization histologic classification of tumors of the breast. It is characterized by inside-out micropapillary morphology, frequent lymph vessel invasion (LVI), and lymph node metastasis; however, its etiology remains unknown. This study investigated the incomplete inside-out growth pattern (IGP) in invasive ductal carcinoma, not otherwise specified (NOS), and examined the association between incomplete IGP and clinicopathologic features, including the presence of intratumoral lymph vessels (ILV), LVI, nodal metastasis, and prognosis. Tumor tissues from 166 invasive duct carcinomas NOS and 10 IMPCs were immunostained using an anti-epithelial membrane antigen antibody to detect IGP and with D2-40 antibody to determine the presence of ILV and LVI. Incomplete IGP was detected focally in 88 (53%) of 166 invasive duct carcinomas NOS. Transition areas between IMPC and invasive duct carcinoma NOS also showed prominent incomplete IGP in 9 (90%) of 10 IMPCs. Incomplete IGP in invasive duct carcinomas NOS was associated with larger tumor size, higher frequencies of ILV, LVI, nodal metastasis, and poorer recurrence-free survival by univariate analysis. Incomplete IGP, ILV, and tumor size independently affected LVI by multivariate analysis. These findings indicate that incomplete IGP of tumor cell clusters is not uncommon and is a useful tool for predicting LVI in invasive duct carcinoma NOS of the breast.     

Cytologic differential diagnosis of papillary pattern in breast aspirates: correlation with histology

Papillary neoplasms, fibroadenoma, fibrocystic change, low-grade ductal carcinoma, and apocrine carcinoma are among "gray zone" lesions in breast cytology. They often have cellular smears with a papillary or pseudopapillary pattern. To better define cytologic criteria useful in distinguishing these entities, we correlated them with histology. Papanicolaou and giemsa stained smears from 33 aspirates and their corresponding histology were reviewed. Of these, 28 had an initial cytologic diagnosis or suspicion of papillary neoplasm, while five cases were not diagnosed cytologically as papillary but the histologic diagnosis was a papillary neoplasm. Cytologic features evaluated included cellularity, architecture, apocrine/single/columnar cells, nuclear atypia, intranuclear inclusions, calcifications, background, myoepithelial cells, and bipolar, naked nuclei. Discriminating cytologic features grouped by final histologic diagnosis were as follows: Papillary neoplasm (14 cases): Hemorrhagic/cystic background, 3-dimensional papillary clusters, columnar cells, and fibrovascular cores. Myoepithelial cells within clusters and background naked, bipolar nuclei were inconspicuous. Fibroadenoma (4 cases): Two-dimensional branching clusters often with folding, moderate myoepithelial cells in clusters, moderate to numerous background bipolar nuclei, often forming doublets in smear background, cellular stroma. Ductal carcinoma (11 cases): Papillary ductal carcinoma in situ in 5 of 11 cases, cribriform/tubular architecture in 6 of 11. Absence or paucity of myoepithelial within clusters and background bipolar nuclei was noted. Fibrocystic change (4 cases): Two-dimensional clusters, moderate myoepithelial cells within clusters, and moderate bipolar nuclei in the background. The presence and quantity of myoepithelial cells, bipolar naked nuclei in the background, and ductal cell architecture were the only consistently useful cytologic features in distinguishing breast lesions with a papillary pattern. Ann Diagn Pathol 5:34-42, 2001.     

Adenomyoepithelioma of the breast: a cytologic dilemma. Report of a case and review of the literature

Adenomyoepithelioma of the breast is a rare benign tumor made up of epithelial and myoepithelial cells. The cytologic features of this lesion are not well defined. This report describes the cytologic features of a case of adenomyoepthelioma characterized by hypercellularity and the presence of many atypical epithelial cells, leading to the erroneous diagnosis of adenocarcinoma. Review of the cytology literature shows that this condition frequently mimics the cytologic features of a number of benign and malignant breast lesions, thus representing not only an important potential pitfall in the diagnosis of carcinoma but also a differential diagnosis to consider in a variety of breast lesions.     

Breast carcinoma with micropapillary features: clinicopathologic study and long-term follow-up of 100 cases

To study the clinicopathologic characteristics and prognosis of invasive micropapillary carcinoma of breast (IMPC), 100 cases of invasive breast carcinoma with an IMPC component were reviewed. Compared with invasive ductal carcinoma, not otherwise specified, with similar histologic grades, carcinomas with IMPC were larger sized, had a higher lymph node metastasis rate with more nodes involved per case, and exhibited increased lymphovascular invasion. The presence of IMPC strongly correlated with the more aggressive behavior. No significant association was established between the proportion of the IMPC component and overall tumor size, histologic grade, lymph node metastasis rate, and distant metastasis, but a trend was noted. Long-term follow-up demonstrated a poorer 5-year and 10-year survival rate for patients with breast carcinoma containing an IMPC component. Breast carcinomas with micropapillary features are more aggressive tumors with a poorer prognosis. This specific structure should be carefully evaluated in the surgical pathology examination of breast carcinoma specimens.     

Epithelial inclusion cyst arising in an intramammary lymph node: Case report with cytologic findings

The occurrence of epithelial inclusion cysts (EIC) in axillary lymph nodes is a rare but well recognized entity, arising either from direct implantation or from embryonal rests. Theoretically, EIC can occur in intramammary lymph nodes, but there has been only one prior report of such a lesion. Here, we describe a case of an EIC arising in an intramammary lymph node of a 37‐year‐old woman. This report focuses on the FNA cytologic features of this lesion and its differential diagnoses. On FNA, the EIC arising in an intramammary lymph node was characterized by mature lymphocytes, squamous epithelial cells, and keratinizing material. The presence of squamous cells can lead to the erroneous diagnosis of more common breast lesions, such as squamous cell carcinoma or metaplastic carcinoma. Contrary to these more sinister diagnoses, EIC arising in an intramammary lymph node is a benign condition. As this rare lesion sometimes mimics a neoplasm both clinically and radiographically, awareness of this entity is important to prevent over treatment. Diagn. Cytopathol. 2009. © 2009 Wiley‐Liss, Inc.     

Malignant granular cell tumor.

We report a case of malignant granular cell tumor of the chest wall that recurred in the right breast with axillary lymph node metastases. The recurrent tumor clinically and grossly mimicked a breast carcinoma. Electron microscopy and immunohistochemical techniques were used to confirm the cytologic and histologic diagnosis of granular cell tumor. The importance of true metastases in the diagnosis of malignant granular cell tumor and their differential diagnosis are discussed.     

乳腺浸润性微乳头状癌的形态改变与生物学行为的关系

目的 观察乳腺浸润性微乳头状癌的形态与生物学行为之间的关系。方法 对2088例术前没有作活检取材(仅经细胞学或细针穿刺活检诊断)的乳腺癌乳腺切除标本做全乳腺切片检查,其中浸润性导管癌1880例,观察浸润性微乳头状癌的临床病理学特征及光镜、电镜下的形态学表现。结果 浸润性微乳头状癌的发生率为6．2％(117／1880),其淋巴管侵犯(54．7％,58／106)、淋巴结转移阳性率(76．4％,81／106)及转移的个数(平均9．6)均明显的高于浸润性导管癌。光镜下特征性表现为癌巢由呈集块型或(和)腺管型的微乳头状癌巢组成,与网状间质间形成明显的空隙(主间质分离)。电镜下见癌巢与间质接触侧的细胞表面有大量的微绒毛,与间质的结合弱;癌细胞质内含有丰富的细丝;间质内见丰富的脉管。结论 浸润性微乳头状癌的淋巴管侵袭力强和淋巴结转移率高,这种恶性程度高的生物学行为可能与其癌巢的容易脱离及肿瘤细胞本身所具有的高度运动能力以及富含脉管的网状间质有关。     

Fine needle aspiration cytology of invasive micropapillary carcinoma of the breast

AIM: To determine the pathognomonic diagnostic cytological features of invasive micropapillary carcinoma of the breast which is a poor prognostic subtype of infiltrating ductal carcinoma. METHODS: A series of 20 histologically proven tumours were reviewed retrospectively to evaluate the various cytological features, including tumour morules, isolated malignant cells, staghorn epithelial structures, mucinous background and apocrine metaplasia. RESULTS: Tumour morules formation and isolated malignant cells were the two most reliable and constant cytological features, being present in 75% (15/20 cases) of cases. Staghorn epithelial structures were present in 35% (7 cases). Mucinous background (2 cases, 10%) and apocrine metaplasia (4 cases, 20%) of the tumour cells were seen in a few cases only and did not appear very helpful. CONCLUSION: Tumour morules formation, isolated malignant cells and staghorn epithelial structures are the most reliable cytological features, and the presence of these should raise suspicion of invasive micropapillary carcinoma.     

Cytopathologic differential diagnosis of low‐grade urothelial carcinoma and reactive urothelial proliferation in bladder washings: a logistic regression analysis

Conventional cytomorphologic assessment is the first step to establish an accurate diagnosis in urinary cytology. In cytologic preparations, the separation of low‐grade urothelial carcinoma (LGUC) from reactive urothelial proliferation (RUP) can be exceedingly difficult. The bladder washing cytologies of 32 LGUC and 29 RUP were reviewed. The cytologic slides were examined for the presence or absence of the 28 cytologic features. The cytologic criteria showing statistical significance in LGUC were increased numbers of monotonous single (non‐umbrella) cells, three‐dimensional cellular papillary clusters without fibrovascular cores, irregular bordered clusters, atypical single cells, irregular nuclear overlap, cytoplasmic homogeneity, increased N/C ratio, pleomorphism, nuclear border irregularity, nuclear eccentricity, elongated nuclei, and hyperchromasia (p ? 0.05), and the cytologic criteria showing statistical significance in RUP were inflammatory background, mixture of small and large urothelial cells, loose monolayer aggregates, and vacuolated cytoplasm (p ? 0.05). When these variables were subjected to a stepwise logistic regression analysis, four features were selected to distinguish LGUC from RUP: increased numbers of monotonous single (non‐umbrella) cells, increased nuclear cytoplasmic ratio, hyperchromasia, and presence of small and large urothelial cells (p = 0.0001). By this logistic model of the 32 cases with proven LGUC, the stepwise logistic regression analysis correctly predicted 31 (96.9%) patients with this diagnosis, and of the 29 patients with RUP, the logistic model correctly predicted 26 (89.7%) patients as having this disease. There are several cytologic features to separate LGUC from RUP. Stepwise logistic regression analysis is a valuable tool for determining the most useful cytologic criteria to distinguish these entities.     

Fine-needle aspiration cytology of sclerosing adenosis of the breast: a retrospective review of cytologic features in conjunction with corresponding histologic features and radiologic findings

We retrospectively reviewed 25 fine-needle aspiration cases of sclerosing adenosis of the breast in conjunction with histologic features of the paired core-needle biopsy and radiologic findings. The original cytologic diagnoses were benign (n = 19), focally atypical (n = 3), and suspicious for carcinoma (n = 3). The frequent features, although not specific, were low-to-moderate cellularity, bland epithelial cells that focally formed cohesive groups/tubules or occasionally discohesive clusters or individual cells, and fragments of dense fibrous stroma. Some tubules had an angulated configuration. Myoepithelial cells were present in all cases but were scant or absent in small epithelial groups. These cytologic features closely reflected the histologic appearances (ie, compressed and attenuated tubules and sclerotic stroma), but may cause overinterpretation on cytologic smears, especially when angulated tubules, discohesive or individual epithelial cells, scanty myoepithelial cells, and nuclear atypia are noted concurrently. Familiarity with its cytologic features may prevent false-positive diagnosis. Histologic confirmation is recommended for difficult cases.     

Spontaneous regression of breast cancer with axillary lymph node metastasis: a case report and review of literature

Spontaneous regression (SR) of cancer is a rare but well-documented biological phenomenon. However, the mechanism remains to be elucidated. We herein report a case of the SR of breast cancer at both the primary site and metastatic axillary lymph node with spontaneously-induced T cell-mediated immunological responses. A 52-year-old female with a lump in the left axilla was diagnosed to have a small breast carcinoma with a distinct axillary lymph node metastasis. During the preoperative systemic examination, she was diagnosed to have severe type 2 diabetes mellitus, was treated with insulin, and the hyperglycemia was normalized after one month. Surgery for left breast cancer was then performed. The postoperative histopathological examination revealed the SR of breast cancer at both the primary site and metastatic axillary lymph node. Immunohistochemical studies revealed that estrogen receptor positive, AE1/AE3-positive ductal carcinoma completely underwent necrosis associated with extensive infiltration of CD3-positive T cells in the tumor nodule in the lymph node. In addition, primary ductal carcinoma cells also underwent single cell necrosis with infiltration of T cells with lymph follicle-like organization of B cells in the mammary gland. The features were suggestive that the tumor eradication in the metastatic lymph node and regression of the primary ductal carcinoma could be due to host T cell response to the ductal carcinoma. As far as we know it is the first report that shows the spontaneous regression of breast cancer, probably due to the spontaneously-induced T cell response.     

Breast tumor resembling the tall cell variant of papillary thyroid carcinoma: a case report

The breast tumor resembling the tall cell variant of papillary thyroid carcinoma is a very unusual mammary carcinoma whose histologic and predominant nuclear features mimic a papillary thyroid carcinoma. We report the case of a 64-year-old woman who presented with a palpable nodule in the right breast. Fine needle aspiration disclosed abundant cellularity with isolated cells, sheets, and papillary formations of epithelial cells with nuclear grooves. Histologically, the neoplastic cells were arranged in a solid to papillary architecture, with follicular-like and cribriform areas. The cells were columnar to cuboidal with eosinophilic cytoplasm, clear chromatin, nuclear grooves, and occasional nuclear pseudoinclusions. Tumor cells were positive for cytokeratins, alpha and beta-estrogen receptors, progesterone receptor, androgen receptor, CEA, and bcl-2. We searched for BRAF mutations with negative results. Recognizing the cytologic and histologic characteristics of these peculiar mammary tumors that mimic thyroid carcinomas can avoid unnecessary clinical investigations.