Membrane connectivity estimated by digital image analysis of HER2 immunohistochemistry is concordant with visual scoring and fluorescence in situ hybridization results: algorithm evaluation on breast cancer tissue microarrays

Because metaplastic carcinoma of the breast encompasses a great variety of histopathology, diagnostic challenges abound, especially within the realm of cytology. The authors compiled and studied an eight-case series comprised of metaplastic breast carcinomas and lesions initially suspicious cytologically for metaplastic carcinoma in order to assess the degree of cytologic-histologic correlation and to identify recurring problematic themes surrounding the cytology-based diagnosis of this neoplasm. The cytologic and histologic slides from eight cases suspicious for metaplastic breast carcinoma diagnosed by fine needle aspiration (FNA) were collected and analyzed through a seven-year retrospective search of case files at our institution. Based on cytologic characteristics, the cases were separated into three groups. Group 1 consisted of three cases presenting with poorly differentiated adenocarcinoma and squamoid components on FNA. Group 2 was composed of two cases that featured a monophasic, malignant ductal cell population on cytology, while the cytologic specimens for the third group of cases presented with a mesenchymal component with or without a malignant glandular constituent. Cytologic-histologic correlation was present in two of three cases demonstrating a mesenchymal component, and there was 100% sensitivity in the cytologic detection of those mesenchymal elements. However, in only one of three cases was there an accurate cytologic diagnosis of metaplastic carcinoma when squamoid changes were present on FNA. Both cases demonstrating only malignant glandular elements on cytologic specimens revealed an additional component of malignant squamous differentiation upon the examination of mastectomy-derived tissue. These results indicate that squamous-like changes identified on FNA should be interpreted with caution and that sampling error remains a problematic recurrence in cytology. Regardless, there appears to be promise concerning the accurate cytologic diagnosis of metaplastic carcinoma when the lesion is characterized by a mesenchymal component. A study implementing a larger case number is essential in determining the significance of these findings.     

Metaplastic carcinomas of the breast—fine needle aspiration (FNA) cytology findings

nogueira m., andré s. and mendonça e. . (1998) Cytopathology 9, 291–300
Metaplastic carcinomas of the breast—fine needle aspiration (FNA) cytology findings
Metaplastic carcinomas of the breast are defined by mesenchymal and/or squamous cell components associated with ductal carcinoma and may raise diagnostic problems in FNA cytology. We reviewed FNA smears of a series of nine cases; seven were compared with histological sections and two with cell-block sections. The cytological pattern was diagnostic of carcinoma in six cases; in two cases a diagnosis of sarcoma/phyllodes tumour was considered, as cells were predominantly spindle-shaped. One case had a pleomorphic adenoma type pattern. The cytological findings suggesting a diagnosis of metaplastic carcinoma include a liquid aspirate, a proteinaceous or chondromyxoid background and a poorly differentiated tumour with multinucleated giant cells, neoplastic or histiocytic. A definite diagnosis requires the presence of both carcinomatous and metaplastic (squamous/mesenchymal) components.     

Mixed apocrine-medullary carcinoma of the breast. Report of a case with fine needle aspiration cytology

The case of an unusual variant of breast carcinoma arising in an 80-year-old woman is presented. Fine needle aspiration (FNA) cytology of this carcinoma revealed sheets of cells showing apocrine differentiation and significant cellular atypia mixed with lymphocytes and plasma cells. At mastectomy, the neoplasm was found to have features of both apocrine carcinoma and medullary carcinoma, with a prominent lymphocytic infiltrate. This case underlines the difficulty in distinguishing between malignant apocrine cells and apocrine metaplastic cells by FNA cytology. The presence of an inflammatory component, as seen in this case, may compound such difficulties.     

Carcinoid tumor metastatic to breast diagnosed by fine needle aspiration. Case report and literature review

Fine needle aspiration (FNA) biopsy was used to study a mass in the left breast in a patient with a previous history of an ileal carcinoid tumor and later lymph node metastases who presented with bilateral palpable breast masses. The FNA specimens showed the lesion to be a carcinoid tumor. The metastatic nature of the lesion was proven by positive restaining of FNA smears by both the Sevier-Munger technique (demonstrating abundant argyrophilic cytoplasmic granules) and the Fontana-Masson method (showing argentaffin cytoplasmic granules). The distinction between primary and metastatic carcinoid tumors of the breast is discussed, as is their origin and their differentiation from other malignancies of the breast.     

Diagnostic pitfalls in fine needle aspiration cytology of atypical apocrine metaplasia in a breast lesion. A case report

BACKGROUND: Apocrine metaplastic cells are frequently encountered in fine needle aspirates of breast lesions. Atypical apocrine metaplastic cells with signet ring features can also occur, and their presence may present a diagnostic dilemma in the differentiation of benign versus malignant lesions. CASE: A fine needle aspirate of a 2.5 x 1.0-cm, subareolar mass in a 47-year-old female showed atypical cells with signet ring morphology. Also present were clusters of cells that were enlarged and showed nuclear atypia, prominent nucleoli and cytoplasmic granules. Papillary cohesive clusters of ductal cells were also identified. The fine needle aspiration diagnosis was mucinous carcinoma. The nodule was excised, and the histologic diagnosis was sclerosing ductal papilloma with atypical apocrine metaplasia. CONCLUSION: Atypical apocrine cells can be misinterpreted as mucinous carcinoma or usual duct adenocarcinoma on fine needle aspiration cytology. We present clues that may help in rendering the correct interpretation.     

乳腺化生性癌的病理特征、复发和生存情况分析

目的:探讨乳腺化生性癌的病理特征、复发和生存情况。方法:选取我院于2002年1月至2015年12月期间收治的7例乳腺化生性癌患者临床病历资料进行回顾性分析,讨论乳腺化生性癌的病理特点和鉴别诊断、组织起源以及治疗预后等。结果:7例乳腺化生性癌PR、ER和HER-2均显示为阴性,广谱CK则显示为阳性;所有入选患者均显示EGFR阳性,其中有3例患者显示p53阳性,4例患者显示CK5/6阳性。此外,3例患者经腋窝淋巴结清扫后显示有2例患者出现腋窝淋巴结转移,4例患者经前哨淋巴结活检后结果:显示无癌转移。结论:乳腺化生性癌在临床上属于乳腺癌中较为罕见的亚型,其生物学行为和生存预后均不佳,HER-2和PR、ER等多显示为阴性,容易复发,目前主要治疗方法:为在手术治疗的基础上加以放射治疗。     

Fine needle aspiration cytology of invasive micropapillary (pseudopapillary) carcinoma of the breast. Report of 11 cases with clinicopathologic findings

OBJECTIVE: To describe the cytologic features of invasive micropapillary carcinoma of the breast, a distinct, unusual variant of infiltrating duct carcinoma characterized histologically by pseudopapillary structures lacking fibrovascular cores and tubuloalveolar structures floating freely within clear spaces separated by a delicate fibrocollagenous stroma and characterized clinically by prominent lymphotropism and an aggressive clinical course. STUDY DESIGN: We reviewed the clinical, cytologic, histologic, immunohistochemical and flow cytometric features in 11 cases of invasive micropapillary carcinoma of the breast diagnosed preoperatively by fine needle aspiration. RESULTS: All patients were women, ranging in age from 31 to 83 years. A preoperative diagnosis of malignancy was made in all cases. Tumor size ranged from 1.2 to 5.5 cm. Ten patients had lymph node metastases. Cytology was characterized by a "dual" pattern formed by round or angulated, three-dimensional, cohesive clusters of neoplastic cells with pseudopapillary configuration and two-dimensional, dyscohesive aggregates and single cells with high grade nuclei and intact cytoplasm.     

Fine needle aspiration of benign and malignant breast masses associated with pregnancy.

Of 1,612 fine needle aspirates (FNA) of breast lesions performed over a seven-year period, 25 cases (1.5%) were identified as breast masses associated with pregnancy. Patients ranged in age from 16 to 46 years, with a mean of 27. Gestational age at the time of FNA ranged from three months to three months postpartum or following breast-feeding. Cytologic diagnoses of these pregnancy-associated breast masses were: galactocele (5 cases, 20%), lactating adenoma (9 cases, 36%), fibroadenoma with lactational change (7 cases, 28%), juvenile fibroadenoma with lactational change (1 case, 4%), atypical reactive duct cells with lactational change (1 case, 4%) and infiltrating duct carcinoma (2 cases, 8%). The degree of lactational change varied proportionately with gestational age. None of the 22 patients with benign cytologic diagnoses of galactocele, lactating adenoma or fibroadenoma subsequently developed carcinoma. The mean clinical follow-up for these 22 patients was 27 months. Three cases of fibroadenoma and the case of juvenile fibroadenoma were confirmed by surgical excision. Biopsy of the lesion cytologically diagnosed as atypical reactive duct cells with lactational change revealed infiltrating duct carcinoma (IDC). All three patients with IDC had involvement of multiple axillary lymph nodes, and 1 patient had widely metastatic disease. In two cases of IDC the background lactational breast epithelium exhibited marked cytologic atypia that closely resembled the IDC. Pregnancy-related cellular atypia potentially results in a false-positive diagnosis of breast carcinoma on FNA. FNA is useful in distinguishing benign breast masses of pregnancy from those with marked cytologic atypia requiring surgical biopsy and may minimize the delayed diagnosis of carcinoma associated with pregnancy.     

Fine needle aspiration of metastatic epithelioid angiosarcoma: a report of 2 cases

BACKGROUND: Epithelioid angiosarcomas (EAs) are uncommon mesenchymal tumors occurring in the thyroid, deep-seated soft tissues, parenchymal organs and, more rarely, superficial soft tissues of the head and neck. Due to their cytologic and immunocytochemical presentation on fine needle aspiration cytology (FNAC) samples, these neoplasms may closely mimic a number of different tumors, potentially causing an erroneous cytopathologic diagnosis unless immunophenotypical markers of vascular differentiation are sought in the cellular material. CASES: A 68-year-old man with a 1-year history of total thyroidectomy for EA presented with a suspicious right neck node and underwent FNA. A 63-year-old woman with a history of recurring multiple scalp nodules diagnosed as EA ultimately developed small multiple, bilateral lymph nodes in the neck and underwent FNA. In both cases a cytopathologic diagnosis of metastatic EA was made. CONCLUSION: The cytopathologic diagnosis of EA is a challenge. Knowledge of the clinical history is of great help in diagnosing metastatic lesions. The cytopathologicpicture of metastases is a useful way for cytopathologists to gain confidence with presentaton of this rare entity in primary sites on FNAC samples. Cytopathologic hints of vascular differentiation should be sought in the cytopathologic material when a diagnosis of EA is entertained.     

Fine needle aspiration biopsy of Ki-1-positive large-cell "anaplastic" lymphoma.

The cytopathologic, immunohistochemical and ultrastructural features of a case of Ki-1-positive lymphoma are presented and discussed. On fine needle aspiration (FNA) biopsy smears, the Ki-1-positive lymphoma was characterized by large isolated cells with abundant dense/vacuolated cytoplasm and large nuclei with irregular profiles. Although most cells contained one nucleus, binucleated and multilobed/multinucleated cells were also seen. The cohesion of the malignant cells in histologic sections of a biopsied lymph node suggested an anaplastic carcinoma. The discrepancy was resolved by ultrastructural and immunologic analyses. The main differential diagnoses on FNA material include Hodgkin's disease, malignant melanoma and undifferentiated carcinoma; the cytologic suspicion should be confirmed by immunocytochemical studies.     

Lung carcinoids. Tumor angiogenesis in relation to clinicopathologic characteristics

OBJECTIVE: To evaluate the prognostic value of carcinoid angiogenesis for the presence of lymph node metastases, histologic subtype and tumor size. STUDY DESIGN: The study group consisted of 72 resected primary lung carcinoids, 57 typical and 15 atypical. TNM staging was performed. The histologic criteria for carcinoids was based on the Flieder classification. Angiogenesis, expressed as tumor microvessel density, was estimated in sections stained with CD34 antibody, according to Weidner's method. RESULTS: The size of carcinoids was related to the histologic type: the average tumor diameter of typical carcinoids was significantly smaller than the average diameter of atypical carcinoids (P = .003, U = 207, Z = -3.023). Atypical carcinoids represented a more aggressive form of tumors than typical carcinoids; patients with typical carcinoids developed lymph node metastases less frequently (10% vs. 33%) as compared to patients with atypical carcinoids; the difference was statistically significant (P = .032). Tumor angiogenesis failed to distinguish the histologic type of carcinoids and did not indicate the presence or absence of regional lymph node metastases; neither did pTN stage or tumor size. CONCLUSION: Angiogenesis is not a determining factor of the metastatic potential of pulmonary carcinoids.     

Stereotaxic fine needle aspiration cytology of clinically occult malignant and premalignant breast lesions

Stereotaxic fine needle aspiration (FNA) cytology was used to study clinically occult (nonpalpable) breast lesions in 114 consecutive patients with mammographically suspicious findings prior to excisional biopsy. The aspirate contained insufficient material for cytologic evaluation in 15 cases (13.2%), which were histologically diagnosed as benign (7 cases), atypical hyperplasia (7 cases) or carcinoma in situ (1 case). The cytologic findings indicated a benign lesion in 77 cases (67.5%), which were histologically diagnosed as benign (71 cases) or atypical ductal hyperplasia (6 cases). The cytologic sample showed atypia in eight cases (7.0%), which were histologically diagnosed as severe atypical ductal hyperplasia (three cases), carcinoma in situ (one case) or proliferative fibrocystic disease (four cases). In the eight cases (7.0%) cytologically interpreted as probably malignant, histology confirmed six invasive carcinomas, one carcinoma in situ and one fibrocystic disease. Of six cases (4.4%) cytologically reported as malignant, five were histologically diagnosed as invasive carcinoma and one as carcinoma in situ. Overall, stereotaxic FNA cytology reported as malignant or probably malignant 14 of the 15 cases with a histologic confirmation of malignancy, for a sensitivity of 93.3%. Cytology correctly identified 78 of the 83 histologically negative cases, for a specificity of 94.0%. The 16 cases histologically diagnosed as ductal hyperplasia, which carries a high risk for subsequent malignancy, were studied in detail in an effort to define histologic and cytologic criteria for this entity. Using selected histologic criteria, 11 of these cases were graded as showing mild-to-moderate atypical hyperplasia and 5 as showing severe atypical hyperplasia. Three of the latter cases were similarly identified by an analogous cytologic grading; the other two cases had insufficient cytologic samples. The total results in this series of 114 cases support the use of stereotaxic FNA cytology in the diagnosis of these nonpalpable breast lesions, examples of which are illustrated. In particular, it may help to raise the low specificity yielded by mammography alone, which would represent a significant advance for the patient in terms of the accuracy, expediency and reduced cost of diagnosing these lesions.     

Fine needle aspiration of breast lesions in women aged 30 and under

Fine needle aspiration (FNA) biopsies of 1,598 breast masses were performed between 1983 and 1989, and of them, 48 were from women aged 30 and under for whom a cytologic diagnosis was made by FNA and histologic follow-up was available. In 37 (77%) of the cases, both the cytologic and histologic diagnoses were benign. Fibroadenoma (20/37) and fibrocystic changes (14/37) were the most common benign lesions aspirated. Eight (17%) FNAs showed cytologic atypia. Four of these atypical lesions proved to be benign (two fibroadenomas, two fibrocystic changes). Epithelial proliferation in fibroadenomas and fibrocystic changes and cellular stroma in a fibroadenoma mimicking phylloides tumor were the causes of atypia in these biopsies. Four of the eight atypical lesions were shown to be carcinoma at biopsy (three infiltrating duct, one atypical medullary). Low cellularity, epithelial cohesiveness mimicking a fibroadenoma and background lactational changes in a pregnant patient were the causes of the atypical, rather than unequivocally malignant, diagnoses in these cases. In three patients (6%), a diagnosis of carcinoma was made by FNA and confirmed histologically (all were infiltrating duct carcinoma). Although most breast masses in women aged 30 and under are benign, cytologic atypia in a breast fine needle aspirate in this age group warrants a surgical biopsy. Clinical follow-up alone may be appropriate for young women with clinically nonsuspicious breast masses without cytologic atypia.     

Diagnostic value of fine needle aspirates processed by ThinPrep® for the assessment of axillary lymph node status in patients with invasive carcinoma of the breast

X. Jing, E. Wey and C. W. Michael Diagnostic value of fine needle aspirates processed by ThinPrep® for the assessment of axillary lymph node status in patients with invasive carcinoma of the breast Objective: To evaluate the utility of ThinPrep® as an optional specimen processing method for the detection of axillary lymph node metastasis of invasive breast carcinoma. Methods: A computer SNOMED search from the file at our institution between January 2003 and August 2011 retrieved a total of 209 fine needle aspiration (FNA) specimens of axillary lymph nodes prepared by ThinPrep and followed by axillary lymph node biopsy and/or dissection. Original cytological diagnoses and corresponding histological diagnoses were documented. Using the histological diagnoses as the gold standard, the diagnostic parameters including sensitivity, specificity, positive (PPV) and negative predictive values (NPV) and diagnostic accuracy were calculated. Both cytology and histology slides from cyto‐histologically discrepant cases were reviewed. Results: Out of a total of 209 specimens, 193 (92%) had adequate diagnostic material while the remaining 16 specimens (8%) were inadequate for cytological assessment. The diagnostic specimens included 168 invasive ductal carcinomas (IDC), 15 invasive lobular carcinomas (ILC) and 10 mixed carcinomas (IDC and ILC). Excluding 19 cases with malignant cells on FNA in which no residual tumour was found in fibrotic lymph nodes after neoadjuvant therapy (cytology and histology confirmed on review) ThinPrep detected nodal metastasis with an overall sensitivity of 77.5%, specificity of 100%, PPV of 100% and NPV of 53.7%. Diagnostic accuracy was 82.2%. There was no difference in Bloom–Richardson grade or the number or size of metastases between tumours with true‐positive and false‐negative cytology. Sampling error was the sole factor contributing to cyto‐histological discrepancy. Conclusions: ThinPrep is a good alternative to the conventional smear for cytological assessment of axillary lymph node status in patients with invasive breast carcinoma, particularly when specimens are collected at remote sites or when cytologists are not available for assistance during FNA.     

Thyroid papillary microcarcinoma. Is it really a pitfall of fine needle aspiration cytology?

OBJECTIVE: To assess the role of fine needle aspiration (FNA) of the thyroid in the diagnosis of papillary microcarcinoma. STUDY DESIGN: Eight cases of papillary microcarcinoma were diagnosed by fine needle aspiration. On histologic examination they were found to be adjacent to larger nodules of interest. The microcarcinomas were inadvertently sampled when sampling the larger, dominant nodules. RESULTS: None of the eight dominant nodules were papillary carcinoma; seven were benign lesions, and one was an angioinvasive Hürthle cell carcinoma. In three cases the microcarcinomas were situated within the capsule of a hyperplastic nodule. On histologic examination, five cases had multifocal microcarcinomas, with one case having multiple lymph node metastases. Based on the clinical findings and morphologic features, there were no definitive cytologic findings that could distinguish between "incidental" microcarcinoma and clinically significant papillary carcinoma. CONCLUSION: The detection of microcarcinoma by FNA should not be considered a false positive finding since the exact nature of the lesion cannot be determined until complete histologic evaluation reveals it to be truly incidental and clinically insignificant.     

Apocrine adenocarcinoma of the vulva with associated Paget's disease. Diagnosis of lymph node metastases by fine needle aspiration biopsy

The cytologic features of a fine needle aspiration biopsy of lymph node metastases from a vulvar adenocarcinoma with apocrine differentiation are documented. Cytologic findings that suggested apocrine differentiation included extreme nuclear eccentricity, punctate eosinophilic cytoplasmic granules and moundlike protrusion of apical cytoplasm. The cytologic findings correlated well with the histologic and histochemical features of the primary vulvar adenocarcinoma and its lymph node metastases.     

Fine needle aspiration cytology of a thyroid metastasis of metaplastic breast carcinoma: a case report

BACKGROUND: Metaplastic breast carcinoma is defined as mesenchymal and/or squamous cell components associated with ductal carcinoma. Because of the heterogeneous nature of this tumor, cytologic interpretation on fine needle aspirates can be quite challenging. This is especially true of metastatic lesions of this rare tumor type. Metastasis to the thyroid has not been previously reported. CASE: A 57-year-old woman with a history of metaplastic breast carcinoma for which she underwent mastectomy, chemotherapy and radiation therapy 2 years earlier presented with a fast-growing left thyroid mass with progressive hoarseness and dysphasia. Clinical presentation and findings from a neck computed tomographic scan were strongly suggestive of a primary thyroid malignancy. The aspirate specimen was composed of scant, highly atypical epithelial cells in a background of an abundant chondromyxoid matrix and scattered, benign follicular cells. A literature review confirmed the novelty of this case. CONCLUSION: This case emphasizes the value of clinical information and the importance of generous sampling in achieving a correct diagnosis of metastatic metaplastic carcinoma.