Cytokeratin is a superior marker for detection of micrometastatic biliary tract carcinoma

BACKGROUND: The incidence of lymph node micrometastases in patients with biliary tract carcinoma is unknown. We evaluated the utility of three antibodies for immunohistochemical (IHC) detection of micrometastatic disease in patients with gallbladder and bile duct carcinoma. MATERIALS AND METHODS: Surgical specimens from 35 patients with biliary tract carcinoma were evaluated. Histologically involved tissues were stained with the following antibodies using standard IHC techniques: cytokeratin (AE1:AE3), CEA (carcinoembryonic antigen), and EMA (epithelial membrane antigen). The antibodies with the greatest degree of positive staining were then used to evaluate the lymph nodes of patients with histologically negative lymph nodes. Micrometastatic disease was defined as clustered atypical cells <2 mm in size detected only with the use of IHC. RESULTS: All of the primary tumors and histologically positive lymph nodes demonstrated staining with cytokeratin and CEA antibodies, whereas only 83% were positive for EMA. Therefore, cytokeratin and CEA antibodies were used to evaluate histologically negative lymph nodes. Anti-cytokeratin immunostaining detected micrometastatic disease in two patients. Staining with anti-CEA was negative in all specimens. Overall, two of 15 patients with histologically node negative biliary tract carcinoma had occult micrometastases. CONCLUSION: Cytokeratin immunostaining enables detection of micrometastases in histologically negative lymph nodes in patients with biliary tract carcinoma. Prospective protocols incorporating cytokeratin staining of the lymph nodes may help determine the incidence and clinical significance of occult micrometastatic disease in these patients.     

A Case of Adenomyoepithelioma of the Breast Showing Strong Uptake of 18F‐Fluorodeoxyglucose on a Positron Emission Tomography

An adenomyoepithelioma of the breast is a rare tumor characterized by biphasic proliferation of both epithelial and myoepithelial cells. This tumor is generally considered as a benign neoplasm, and there are few reports describing the imaging features of this tumor through ¹⁸F‐fluorodeoxyglucose positron emission tomography (FDG‐PET). Here, we report a case of an adenomyoepithelioma that showed strong uptake of FDG on PET similar to that observed with a malignant tumor. A 73‐year‐old woman presented to our hospital with a 3.5‐cm, mobile, and elastic hard tumor in the upper area of the left breast. Although the findings of mammography, ultrasonography, and contrast‐enhanced magnetic resonance imaging suggested that the tumor was malignant, it was diagnosed as an adenomyoepithelioma by core needle biopsy. An invasive ductal carcinoma, 0.5‐cm in size, was detected in the medial upper area of the ipsilateral breast during an examination. Although FDG‐PET demonstrated no lymph node or distant metastases from the invasive ductal carcinoma, strong uptake of FDG was detected in the adenomyoepithelioma. Breast conserving surgery and sentinel lymph node biopsy for the invasive ductal carcinoma together with resection of the adenomyoepithelioma was performed. A diagnosis of adenomyoepithelioma was confirmed through histologic examination of the resected specimen. This case indicates that some adenomyoepitheliomas may show a strong uptake of FDG on PET, which resembles a malignant tumor.     

Myoepithelial lesions of the breast. Myoepitheliosis, adenomyoepithelioma, and myoepithelial carcinoma.

The clinical and pathologic features of 31 breast lesions composed of a prominent proliferation of myoepithelial cells either admixed with epithelial cells or in pure form were studied. The lesions were divided into three categories: myoepitheliosis, adenomyoepithelioma, and malignant myoepithelioma (myoepithelial carcinoma); the latter is the only lesion composed purely of myoepithelial cells. Three multifocal, microscopic lesions located in the peripheral duct system were designated as myoepitheliosis. Twenty-seven solitary, grossly palpable, predominantly centrally located lesions qualified as adenomyoepithelioma. These were further subdivided into spindle-cell, tubular, and lobulated variants. Two lesions in the latter group had a carcinoma arising within them. Only one case, which was characterized by a solitary mass composed of an infiltrative spindle cell proliferation, qualified as malignant myoepithelioma (myoepithelial carcinoma). Two patients with adenomyoepithelioma developed recurrences; one tumor was of the tubular type, the other of the lobulated type. Both of these tumors had irregular margins. One of these patients had two recurrences and is currently well 8.5 years after the initial excision. The second patient developed a recurrence 8 months after initial excision; the recurrence presented as multiple nodules. One of the patients with myoepithelial carcinoma arising in an adenomyoepithelioma also developed a recurrence within 2.3 years. Her initial tumor was located in the axillary tail of the breast, and she had axillary node metastasis at the time of presentation. All remaining patients with follow-up are well without evidence of recurrence up to 17.3 years after the initial diagnosis (average follow-up, 6.1 years); one patient died of unrelated causes.     

Anaplastic Paget's disease.

Six cases of a distinct, histologically anaplastic variant of mammary Paget's disease are described. Patients ranged in age from 40 to 85 years. All patients had scaling erythematous lesions confined to the nipple; none had palpable breast masses. Histologically, the lesions had features resembling Bowen's disease, including full-thickness epidermal atypia, loss of nuclear polarity, and marked cytologic anaplasia. Intraepidermal acantholysis was a distinctive feature in all cases. In some biopsies, small groups and single typical Pagetoid cells were seen within the areas of confluent Bowen-like change. Immunohistochemically, carcinoembryonic antigen (CEA) was positive in three of six patients; epithelial membrane antigen (EMA) in five of six patients, and cytokeratin AE1/AE3 in three of six patients. Mucicarmine stains were uniformly negative. In our series, anaplastic Paget's disease was associated with concomitant invasive ductal carcinoma in three of six patients (50%). This percentage is significantly higher than that previously reported for patients with Paget's disease and without palpable breast mass. Histologic features that are helpful in distinguishing between anaplastic Paget's disease and Bowen's include cleft-like acantholysis, absence of dyskeratotic cells, and persistence of basal cell layer. More rarely, but very helpful when present, are underlying ductal carcinoma, intracellular lumina, and associated conventional Paget's disease. Immunohistochemistry results were variable and of relative value. Our study suggests that a nipple lesion histologically resembling Bowen's disease is likely to represent anaplastic Paget's disease.     

Malignant Adenomyoepithelioma of the Breast with Lung Metastases: Report of a Case

Adenomyoepithelioma of the breast is a rare lesion, and has a bicellular pattern of epithelial and myoepithelial cells which are regularly distributed in the tubular structures based on the histologic and ultrastructural features. It is thought to be a benign or a low-grade malignant disease. We herein describe a case of malignant adenomyoepithelioma of the breast with lung metastases in an 86-year-old woman. A primary massive tumor in the left breast grew rapidly within a short period of time. A simple mastectomy with sampling of the axillary lymph nodes was performed. The obtained lymph nodes did not include any metastatic lesions. Malignancy was evidenced by the presence of a high mitotic rate and severe nuclear atypia. Three months after the operation, radiology showed multiple lung metastases, and the patient died 2 weeks thereafter. Reviewing the literature, nine similar cases were reported, and the prognosis of malignant adenomyoepithelioma of the breast with distant metastases was very poor with the time of recurrence varying after initial treatments. Malignant adenomyoepithelioma should be followed up with careful screening for distant metastases. Received: November 16, 2000 / Accepted: May 15, 2001     

Percutaneous excisional biopsy of impalpable breast lesions under ultrasound visualization

Within the last ten years, the development of innovative minimally invasive breast biopsy technologies has made a significant impact on the diagnostic evaluation of impalpable breast lesions. The Mammotome minimally invasive biopsy system is a diagnostic tool used under stereotactic or ultrasound guidance. The minimally invasive biopsies for 143 impalpable breast lesions in 86 patients were performed using the B-ultrasound-guided 8-gauge vacuum-assisted Mammotome system at Jinan Military General Hospital. One hundred and forty-three breast lesions in 86 patients were excised completely using this method. The average biopsy procedure time was 17 min (range, 3–45 min). Clinically, suspicious lesions were satisfactorily confirmed by this system. One hundred and twenty-one lesions were diagnosed as fibroadenoma, nineteen lesions as breast adenosis, one lesion as invasive breast cancer, and two lesions as ductal carcinoma in situ. Skin ecchymosis was found in two patients. One hundred and thirty-two impalpable lesions were completely excised, as demonstrated by the follow-up ultrasound examination. The results suggest that the B-ultrasound-guided Mammotome system may be an efficient tool for the diagnosis and treatment of impalpable breast lesions.     

Immunohistochemical analysis of benign and malignant papillary lesions of the breast

The histocytological diagnostic criteria and recently developed immunohistochemical procedures selective for either the epithelial or the myoepithelial mammary cells have been tested in a series of 60 cases of papillary lesions of the breast. These included 15 benign solitary intraductal papillomas, 41 papillary carcinomas (29 pure and 12 associated with other types of in situ or invasive ductal carcinoma), and four cases of "suspected" papillary carcinomas. Markers for epithelial cells (EMA) and for apocrine metaplasia (GCDFP-15) did not permit a distinction between benign and malignant papillary lesions; however, immunocytochemical staining for CEA using monoclonal antibodies, and for actin (a marker of the myoepithelial cells) was discriminative in this respect. Benign papillomas have a basal layer of actin-rich myoepithelial cells; the cytoplasm of the epithelial cells is CEA negative. Papillary carcinomas lack the myoepithelial layer, except in areas where multiple papillomas are present, associated with ductal or papillary cancer. CEA was detected in 85% of carcinomas. Two of the cases of "suspected carcinoma" lacked myoepithelial cells and were interpreted as carcinomas. It is concluded that the immunocytochemical methods for cell markers can offer valuable data in the study and diagnosis of papillary lesions of the breast; it is difficult, however, to be categorical in borderline cases since in our experience, the behavior of the malignant papillary lesions of the breast is usually favorable. Residual foci of multiple intraductal papillomas were found in seven cases of papillary carcinoma, supporting the pre-neoplastic potential of this condition.     

手持式Mammotome系统在乳腺微创外科中的应用

目的 探讨B超引导下Mammotome系统对乳腺实质病灶的诊治价值及操作技巧。方法对81例87处乳腺病灶行B超引导下Mammotome微创旋切术，评价其对乳腺病灶的诊治效果。结果所有病灶均成功切除。87处乳腺病灶中，70处为纤维腺瘤，6处为腺瘤样增生，8处乳腺增生，1处为重度不典型增生，1处为乳头状增生活跃，1处为乳腺癌。结论手持式Mammotome微创旋切系统可有效治疗乳腺纤维瘤；能明确诊断可疑病灶，降低良性病变手术率。若为恶性可确定癌组织生物学特性并据此进行新辅助治疗。     

Breast cancer pseudometastasis in a sentinel lymph node with cytokeratin-positive debris

We report extensive pseudometastasis detected by immunohistochemical (IHC) staining within a sentinel lymph node. An 83-year-old woman underwent simple mastectomy and sentinel lymph node biopsy (SLNB) for infiltrating ductal carcinoma. Intraoperative frozen section of the SLNB specimen appeared histologically negative for metastasis. IHC staining for cytokeratin in permanent sections, however, showed what was reported as micrometastasis in the subcapsular sinus. Since these cells did not resemble the primary tumor cells morphologically, and had actually been called histiocytes in the frozen section, further IHC staining was done. The subcapsular cells were negative for epithelial membrane antigen (EMA) staining, but they were positive for CD68, a macrophage marker. Thus the cytokeratin-positive cells were not metastatic breast tumor cells, but rather were histiocytes with phagocytized cytokeratin debris. This case report illustrates that IHC staining for cytokeratin in SLNB specimens for breast cancer must be supported by morphologic assessment and further appropriate staining before it can become the basis for treatment decisions.     

Is surgical excision necessary for atypical ductal hyperplasia of the breast diagnosed by Mammotome?

BACKGROUND: Core biopsy findings of atypical ductal hyperplasia (ADH) underestimates the diagnosis of malignancy by 18% to 88%. Using the Mammotome biopsy technique, more accurate assessment of the lesion is possible, making selective excision of these lesions a consideration. METHODS: The records of 62 patients who were found to have ADH at Mammotome biopsy and subsequently underwent excision of the lesion were reviewed. Patient data were statistically analyzed for predictors of malignancy at the time of surgical excision. RESULTS: Of the 62 patients, 9 (15%) had malignancy at excision. Variables predicting for malignancy included markedly atypical hyperplasia and incomplete removal of calcifications at Mammotome biopsy, a previous contralateral breast cancer, and a family history of breast cancer, with a combined sensitivity of 100% and specificity of 80%. CONCLUSIONS: Mild ADH found on Mammotome, not associated with a personal or family history of breast cancer, may not need excision if all calcifications have been removed.     

Diagnostic accuracy of vacuum-assisted biopsy device for image-detected breast lesions

Background : Non‐palpable breast lesions present diagnostic difficulties. Ultrasound‐guided fine‐needle aspiration cytology (FNAC) is a common method used to obtain a diagnosis, but FNAC is frequently inconclusive or insufficiently accurate. Recently a vacuum‐assisted biopsy device (Mammotome^®, Ethicon, Endo‐surgery, USA) has been introduced. The diagnostic accuracy of this biopsy device was assessed for lesions that were visible on ultrasound. Methods : Fifty ultrasound‐guided mammotome biopsies were performed. All were small breast lesions primarily detected by ultrasound. All received FNAC as initial assessment. Mammotome biopsy was performed whenever the breast lesion was considered indeterminate or if it was considered benign and there were associated risk factors such as a family history of breast cancer. Results : Of 50 mammotome biopsies 45 had benign histology. Three of 45 lesions were excised at the patients’ request and were confirmed to be benign. The remaining 42 patients received an ultrasound follow up at 6 months. The lesion size remained static in 39 patients. In three patients the lesion size increased and they were excised and histology was benign. For the four malignancies diagnosed with mammotome biopsy, three patients received definitive treatment and one patient defaulted. There was one failed mammotome biopsy in the present series. Conclusions : Mammotome biopsy is an acceptable diagnostic method for small breast lesions seen on ultrasound. It reduces the need for open biopsy without compromising diagnostic accuracy.     

Behavior of epithelial differentiation antigens (carcinoembryonic antigen, epithelial membrane antigen, keratin and cytokeratin) in transitional cell carcinomas of the bladder.

Results of an immunohistochemical study in normal urothelium and transitional cell carcinomas of the bladder are presented. Paraffin-embedded material was confronted with immunoantisera against carcinoembryonic antigen (CEA), keratin (K), cytokeratin (CK) and epithelial membrane antigen (EMA). Immunohistochemical findings confirm the changes in reactivity of dysplastic urothelium and carcinoma in situ for CEA, CK and EMA, in comparison with normal urothelium. Statistically significant differences were also found, depending upon tumor stage, in staining of transitional cell carcinomas for K and CK. Expression of CK correlated with the tumor differentiation grade: normal urothelium and well-differentiated carcinomas showed a specific pattern of immunostaining for the basal cells, this pattern being lost in poorly differentiated carcinomas.     

560例乳腺良性肿块Mammotome微创旋切术的临床应用

目的探讨B超引导下Mammotome微创旋切系统在乳腺良性肿块切除中的临床应用价值。方法在B超引导下应用Mammotome系统对560例病人896个乳房良性肿块施行微创旋切术。结果所有肿块均被准确、完全切除。每个肿块的切除时间平均为25min,旋切次数20次,皮肤切口0.2～.0.3cm无不良手术并发症发生。结论B超引导下Mammotome微创旋切系统切除乳房良性肿块,操作简易、准确、安全、创伤小,是一项值得推广的乳腺微创技术。     

Myoepithelial Carcinoma: A Rare Neoplasm of the Breast

BACKGROUND: Malignant myoepitheliomas of the breast are extremely rare. There has been a limited number of published reports of myoepithelial carcinomas originating from the breast. CASE REPORT: We describe a malignant myoepithelioma of the breast in a 56-year-old woman. Histological examination showed polygonal epithelioid cells and spindle cells with moderate to marked nuclear atypia. Immunohistochemistry showed reactivity in the spindle cells for smooth muscle actin, cytokeratin (AE1/AE3), and p63, indicating a myoepithelial cell lineage of tumor cells. The patient underwent radical surgical excision of the lesion and axillary lymph node dissection. She demonstrated no evidence of recurrence over an 11-month follow-up. CONCLUSIONS: We suggest myoepithelial carcinomas of the breast be managed with appropriate surgical clearance. A multidisciplinary approach is usually required.     

Sclerosing adenosis of the prostate gland. A lesion showing myoepithelial differentiation.

Sclerosing adenosis of the prostate is a rare lesion characterized by the proliferation of variably sized glands in a cellular stroma. We report light microscopic, immunohistochemical, and ultrastructural studies in 22 examples from 15 patients. Two cases were identified in 100 consecutive prostates embedded by a whole organ method, giving a prevalence of 2%. Antibodies directed against the following antigens were used: high-molecular-weight cytokeratin (CKH; 34 beta E12); cytokeratin (CK; AE1/AE3), prostatic acid phosphatase (PAP), prostate-specific antigen (PSA), S-100 protein, muscle-specific actin (HHF35), and vimentin (Vim). Cells within the glandular component demonstrated positive reactivity for CK, CHH, PSA, and PAP, indicating a prostatic epithelial origin. In addition, a distinct population of cells reacting for muscle-specific actin and S-100 protein was identified within this glandular element. Adequate material for ultrastructural study was available in five cases; all showed the presence of flattened cells located between the basement membrane and secretory epithelial cells, which had features typical for myoepithelial differentiation. Although the prostate gland does not normally contain myoepithelial cells, we have documented their consistent presence in this unusual lesion; we believe these cells arise by a metaplastic process from the prostatic basal cells.     

Solitary cylindroma (dermal analog tumor) of the breast: a previously undescribed neoplasm at this site

The authors report a previously undescribed small, well-demarcated breast tumor similar to a dermal cylindroma in a 63-year-old woman. The tumor was an incidental finding in a lumpectomy specimen for infiltrating lobular carcinoma. The cylindroma was surrounded by normal-appearing breast parenchyma and had the typical "jigsaw" pattern of epithelial basaloid islands. The islands showed focal squamous and myoepithelial differentiation. A notable number of reactive dendritic Langerhans cells permeated the epithelial cell islands, a feature considered to be characteristic of dermal cylindroma. There was also ductal differentiation. Thick bands of hyaline periodic acid-Schiff (PAS) stain and collagen IV-positive basement membrane material bordered the cell islands, and PAS-collagen IV-positive hyaline globules were seen within the cell islands. There was no nuclear pleomorphism or mitotic figures. The cylindroma did not express gross cystic disease fluid protein 15, carcinoembryonic antigen, estrogen and progesterone receptors, or cytokeratin 20 (CK20). There was diffuse and strong immunoreactivity to CK AE1/AE3, and focal reactivity for CK7 and smooth muscle actin. Cylindroma of the breast should be distinguished from adenoid cystic carcinoma and basal cell carcinoma. Although clearly epithelial, the exact histogenesis and cell phenotype of this unusual dermal type cylindroma of the breast are unknown.     

超声引导下Mammotome微创旋切系统在乳腺肿瘤诊治中的应用

目的：探讨B超引导下Mammotome微创旋切系统对乳腺病灶的诊断价值，并探索其用于乳腺纤维腺瘤微创手术的可行性。方法：对289例430处乳腺病灶进行B超引导下Mammotome微创旋切术，通过病理检查与随访评价其对乳腺病灶的诊治效果。结果：Mammotome微创手术操作成功率达100％。皮肤伤口微小，仅3-5mm。无严重并发症。临床及超声诊断为乳腺纤维腺瘤者均在超声实时监控下完全予以切除。92例144处术后6个月。5年获得随访，其中89例141处经临床B超随访复查均未见“复发”迹象，肿瘤被完全切除率为97．9％（141／144）。对可疑病灶及Ⅲ期乳腺癌均取材满意，并能作出明确诊断。结论：B超引导下的Mammotome微创旋切系统对乳腺不同病灶均能作出明确诊断；对小纤维腺瘤成功进行微创切除术，创伤和皮肤伤口小，效果满意，对其他良性小病灶也可避免不必要的手术活检。     

Mammotome乳腺良性肿块微创旋切术的临床应用

目的探讨B超引导下Mammotome微创旋切系统在乳腺良性肿块切除中的临床应用价值。方法B超引导下应用Mammotome系统对98例296处乳房良性肿块施行微创旋切术。结果所有肿块均被准确、完全切除。每个肿块的切除时间平均为25（15～60）min，平均旋切次数20（8～32）次，皮肤切口0.2～0.3cm。未出现活动性出血、皮下淤血、感染等并发症。结论B超引导下Mammotome微创旋切系统切除乳房良性肿块，操作简单、准确、安全、创伤小，是一项值得推广的乳腺微创技术。     

Malignant Adenomyoepithelioma of the Breast: A Review

Malignant adenomyoepithelioma (MAME) of the breast is a rare lesion characterized by dual population of epithelial and myoepithelial cells which one or both components show malignant features. We report a case of MAME of the breast in a 46‐year‐old woman diagnosed by fine‐needle aspiration with extensive review of the literature. Classification, clinical presentation, cyto‐pathologic, and immunohistochemical features are described. This lesion showed both malignant components of epithelial and myoepithelial cells in cytology and histology. The malignancy was convincingly supported by high mitotic figures, pleomorphism, and invasion in tissue sections. This review of MAMEs showed that cyto‐histologic diagnosis is difficult and should be supported by immunohistochemical study.     

Hemangiopericytoma/solitary fibrous tumor of pectoralis major muscle mimicking a breast mass

INTRODUCTIONHemangiopericytoma (HPC)/solitary fibrous tumor (SFT) is a very uncommon tumor of uncertain malignant behavior. In 1942, Stout and Murray first characterized these neoplasms as “vascular tumors arising from Zimmerman's pericytes” and till now hemangiopericytomas and solitary fibrous tumors of the soft tissues are regarded as features of the same entity in the soft tissue fascicle.PRESENTATION OF CASEWe present a case of hemangiopericytoma/solitary fibrous tumor of the pectoralis major muscle in a 33-year-old female. She first noticed a painless mass in her right breast. Ultrasound of the breast revealed a large heterogeneously hypoechoic lesion within the pectoralis major muscle. Fine needle aspiration of the tumor did not produce any meaningful result. The lesion was completely removed by surgical resection. Histologically, the tumor had staghorn-like vasculature and immunohistochemistry for CD34 was positive, whereas desmin, smooth-muscle actin, S-100 protein, cytokeratins (AE1/AE3) and epithelial membrane antigen (EMA) were all negative. A diagnosis of hemangiopericytoma/solitary fibrous tumor was rendered.DISCUSSIONTumors comprising the HPC/SFT spectrum represent a small subset of soft tissue sarcomas and are found virtually at any site in the body. Wide surgical resection can achieve favorable long-term survival.CONCLUSIONDue to the rarity and unpredictable biological potential of these tumors, long-term follow-up is mandatory even after radical resection, because recurrence or development of metastasis may be delayed many years.