Pathology of R4 spiculated lesions in the breast screening programme

Small spiculated carcinomas are indistinguishable from benign radial scar/complex sclerosing lesions on mammography, leading to a radiological assessment of R4 (suspicious, probably malignant). The cytological and pathological features of 80 screen detected R4 spiculated lesions were reviewed. The analysis showed that there were 46 radial scars, of which 38 were benign and 8 (17%) contained foci of ductal carcinoma in situ (DCIS), and 34 spiculated carcinomas. The majority of radial scars showed some degree of epithelial hyperplasia (assessed semi-quantitively) but the cellularity of the lesion as a whole was not related to the presence of DCIS. In 20 cases no aspiration was attempted for cytology but 40% were inadequate and only one lesion containing DCIS had cytology C4 or C5. Diagnosis of radial scar was made in all cases by localization biopsy. The carcinomas ranged in size between 4 and 15 mm (mean 8.9 mm) and were of grade 1 (21 = 63%) or grade 2 (12 = 37%). There were 16 infiltrating ductal carcinomas of no special type, 12 tubular carcinomas, three lobular carcinomas, two ductal and lobular mixed, and one mucinous carcinoma. Only one patient with carcinoma was node-positive. For the carcinomas, 12 (35%) yielded C5 (malignant) cytology allowing pre-operative diagnosis.     

Breast conservation in ductal carcinoma in situ (DCIS): what defines optimal margins?

The introduction of mammographic screening has resulted in a rise in the detection rate of ductal carcinoma in situ (DCIS), currently accounting for one‐fifth of screen‐detected breast cancers. Although 60–70% of DCIS are treated with breast‐conserving surgery (BCS) with or without radiotherapy, the frequency of subsequent surgery to re‐excise positive margins in order to reduce the probability of recurrences remains high. DCIS recurrence is associated not only with financial, health and psychological implications; approximately half these recurrences are invasive disease. An appropriate margin width for patients undergoing BCS for invasive breast cancer has been largely agreed. Although there is a perception that such recommendations may be applicable to DCIS, major differences exist which may affect this application. Importantly, DCIS patients often do not receive systemic adjuvant (endocrine) therapy and not all receive radiotherapy in routine practice. There is evidence that wide margins (i.e. >10 mm) confer better protection against recurrence than positive (i.e. 0 mm) margins; however, there remains a debate concerning the optimum margin width between 0 and 10 mm. Previous studies have demonstrated that radiation therapy may not compensate for lack of re‐excision in those patients with positive or close margins, while wide margins will inevitably compromise cosmesis and patients’ body image perception. This review aims to address the clinical question of the minimal margin width in DCIS treated with BCS that is associated with the lowest recurrence rate and when, therefore, further surgical intervention for re‐excision can be safely avoided. A range of clinical circumstances that might affect this are considered.     

Recurrent intraneural ganglion cysts: Pathoanatomic patterns and treatment implications

The etiology of intraneural ganglion cysts has been poorly understood. This has resulted in the development of multiple surgical treatment strategies and a high recurrence rate. We sought to analyze these recurrences in order to provide a pathoanatomic explanation and staging classification for intraneural cyst recurrence. An expanded literature search was performed to identify frequencies and patterns in cases of intraneural ganglion cyst recurrences following primary surgery. Two univariate analyses were completed to identify associations between the type of revision surgery and repeat cyst recurrences. The expanded literature search found an 11% recurrence rate following primary surgery, including 64 recurrences following isolated cyst decompression (Group 1); six after articular branch resection (Group 2); and none following surgical procedures that addressed the joint (Group 3). Eight cases did not specify the type of primary surgery. In group 1, forty‐eight of the recurrences (75%) were in the parent nerve, three involved only the articular branch, and one travelled along the articular branch in a different distal direction without involving the main parent nerve. In group 2, only one case (17%) recurred/persisted within the parent nerve, one recurred within a persistent articular branch, and one formed within a persistent articular branch and travelled in a different distal direction. Intraneural recurrences most commonly occur following surgical procedures that only target the main parent nerve. We provide proven or theoretical explanations for all identified cases of intraneural recurrences for an occult or persistent articular branch pathway. Clin. Anat. 28:1058–1069, 2015. © 2015 Wiley Periodicals, Inc.     

Over-expression of p53, p21 and Cdc2 in histologically negative surgical margins is correlated with local recurrence of laryngeal squamous cell carcinoma

The aim of this study was to explore the relationship between the expression of p53, p21 and Cdc2 in the early laryngeal cancer with negative pathological margins and its local recurrence. During 2004-2010, a total of 85 patients with early laryngeal cancer were selected in Tangshan Union Hospital, Hebei, China, and immunohistochemical method was used to detect the expression of p53, p21 and Cdc2 in the negative pathological margin tissues. All patients were followed up for two years to collect pathological data for evaluating the survival and tumor recurrence. Two years after surgery 14 of 85 patients with laryngeal cancer presented with recurrence (recurrent group), while 71 patients without recurrence (none recurrent group). The positive rate of p53, p21 and Cdc2 protein in laryngeal cancer tissues was 60.0% (51/85), 38.8% (33/85) and 70.6% (60/85), respectively, while that of the three proteins in the cancer adjacent tissues was 36.5% (31/85), 21.2% (18/85) and 29.4% (25/85), respectively. The differentiation and TNM stage of tumor had no correlation with the three proteins. The positive rate of p53 in the surgical margin of the recurrent group and non recurrent group was 71.4% (10/14) and 29.6% (21/71) (P = 0.003), that of p21 was 50.0% (7/14) and 15.5% (11/71), (P = 0.011) and Cdc2 was 57.1% (8/14) and 23.9% (17/71) (P = 0.030), respectively. In conclusion, p53, p21 and Cdc2 may be involved in the occurrence, development and recurrence of laryngeal squamous cell carcinoma. Overexpression of p53, p21 and Cdc2 in the surgical margin of early laryngeal cancer is closely related to local recurrence of tumor.     

Pathology of the male breast

The male breast encompasses a number of benign and malignant breast conditions. The commonest cause of male breast enlargement is gynaecomastia. This can be physiological, idiopathic or pathological. Male breast cancer (MBC) is a rare disease comprising less than 1% of all breast cancers. The commonest histology is grade 2 ductal no special type carcinoma. Unlike the female breast, papillary in situ and invasive carcinomas are not uncommon in the male breast. MBC is often of the luminal A phenotype, similar to the post menopausal female breast cancer. Here we review a range of benign and malignant lesions of the male breast with a special emphasis on the two most common lesions: gynaecomastia and MBC. We describe the risk factors, pathogenesis, diagnostic criteria and management of those lesions.     

Benign and borderline phyllodes tumors of the breast: Clinicopathologic analysis of 205 cases with emphasis on the surgical margin status and local recurrence rate

BackgroundThe management of benign and borderline phyllodes tumors of the breast with a positive surgical margin is still controversial. Our aim in this study was to evaluate the impact of surgical margin status on the local recurrence rate of benign and borderline phyllodes tumors.MethodsWe reviewed 205 phyllodes tumors (191 benign, 14 borderline) that were surgically excised at our hospital between 2005 and 2019. Follow-up information extending to at least 6 months after surgery was retrieved from the clinical, radiology, and pathology records.ResultsThe initial surgical margin was negative in 54 (26%) cases, close (≤ 1 mm) in 29 (14%) cases, and positive in 122 (60%) cases. Approximately half of the cases with a close margin and two-third of the cases with a positive margin underwent re-excision to obtain negative margins. Three (2.3%) local recurrences were observed among 131 cases with follow-up information, all three with benign phyllodes tumor. Of these three patients, one had a positive final margin, and two had negative final margins. There was no significant difference in the rate of local recurrence between PT with a positive surgical margin versus a close and negative margin.ConclusionThe study results suggest that close clinical and radiologic follow-up may provide a better course of management rather than re-excision when managing positive margins in benign and borderline phyllodes tumors.     

Induction of membrane-type matrix metalloproteinase 1 (MT1-MMP) expression in human fibroblasts by breast adenocarcinoma cells

Membrane-type matrix metalloproteinase 1 (MT1-MMP) has been recently described as an activator of proMMP-2 (MMP-2) which is involved in tumor invasion. We have shown by in situ hybridization that MT1-MMP is produced by stromal cells in close contact to preinvasive and invasive tumor cells of breast carcinomas. Of particular interest was the observation that some fibroblasts express this enzyme in focal areas in preinvasive lesions, suggesting that particular tumor cells may stimulate fibroblasts to produce MT1-MMP. We have therefore compared the ability of two different breast cancer cell lines, one non-invasive (MCF7) and one invasive (MDA-MB-231) to stimulate MT1-MMP production in human fibroblasts with consequent proMMP-2-activation. The MDA-MB-231 conditioned medium induced MT1-MMP mRNAs in human fibroblasts and a parallel activation of proMMP-2 whereas MCF7 conditioned medium did not have any effect. These results suggest the existence of soluble factor(s) secreted by invasive or some preinvasive breast tumor cells which stimulate fibroblasts to produce and activate MMPs, and emphasize the cooperation between cancer and stromal cells in tumor invasion.     

乳腺癌转铁蛋白受体的临床病理观察

应用抗转铁蛋白受体(TrfR)单克隆抗体(OKT_9)对52例乳癌组织冰冻切片进行免疫组织化学染色,观察TrfR在乳癌组织中的表达及其与临床病理特征的关系。结果显示:①TrfR阳性率为86.5%,它在癌组织中的表达以肿瘤浸润的边缘较中央略强,在细胞内表现为膜浆型;②TrfR在单纯癌及组织学Ⅲ级中表达较强;③TrfR在晚期病例、肿块>2cm者阳性率及强阳性率较高,在淋巴结转移组强阳性病例亦较多。提示TrfR的表达与肿瘤细胞的分裂增殖和侵袭力有关,具有一定的潜在预后价值。     

Impact of intratumoral heterogeneity on the metabolic profiling of breast cancer tissue using high-resolution magic angle spinning magnetic resonance spectroscopy

High-resolution magic angle spinning (HR-MAS) magnetic resonance spectroscopy (MRS) is a useful metabolic profiling technique for human tissue. However, the impact of intratumoral heterogeneity on the metabolite levels of breast cancers is not yet established. The purpose of this prospective study was to investigate whether the tumor cell fraction of core needle biopsy (CNB) specimens of breast cancers affect metabolic profiles assessed with HR-MAS MRS. From June 2015 to December 2016, 46 patients with 47 breast cancers were enrolled. HR-MAS MRS was used for the metabolic profiling of 285 CNB specimens from the 47 cancers. Multiple CNB samples (range 2–8) for the HR-MAS MRS experiment were obtained from surgical specimens under ultrasound guidance following surgical removal of the tumor. Tumor cell fraction was expressed as a percentage of the tumor cell volume relative to the total tumor volume contained in each CNB sample. Metabolite quantification levels were compared according to primary tumor characteristics using the t-test. Multivariate analyses were performed including primary tumor characteristics and tumor cell percentages as variables. Correlations between tumor cell percentage and metabolite levels in the CNB specimens were assessed according to the immunohistochemical status of the primary tumor. In univariate analysis, levels of choline-containing compounds, glutamate, glutamine, glycine, serine, and taurine were correlated with primary tumor characteristics. In multivariate analysis, most metabolite levels were not affected by tumor cell percentage. Tumor cell percentage showed poor correlation with metabolite levels in hormone receptor-positive cancer and triple-negative cancer, and poor to fair correlation with metabolite levels in HER2-positive cancer. This study showed that differences in the tumor cell fraction of CNB samples do not affect predictions on the primary cancer from which the samples are obtained.     

Is core needle biopsy superior to fine‐needle aspiration biopsy in the diagnosis of papillary breast lesions?

Since the 1980s core needle biopsy (CNB) has gained remarkable popularity and in many institutions it has replaced fine-needle aspiration biopsy (FNAB). However, similar to FNAB, limitation remains in the ability of this procedure to reliably diagnose a small, but prognostically significant, number of breast lesions. These include entities such as atypical ductal hyperplasia, fibro-epithelial tumors, radial scar, papillary lesions, and lobular neoplasia. To assess the diagnostic accuracy of CNB vs. FNAB in the same breast lesions, we reviewed our cases of papillary lesions of the breast. In a retrospective study, we identified 36 cases of FNAB and 11 cases of CNB diagnosed as papillary lesions and compared the results with their corresponding surgical specimen. Interpretation ranged from papillary vs. atypical papillary lesions favoring benign vs. malignant tumors, respectively. Occasionally, definitive diagnosis of papillary carcinoma was entertained. Immunohistochemical staining with smooth muscle actin was used to evaluate the presence or absence of a myoepithelial cell layer. FNAB had benign findings in 21 lesions, atypical in 10, and malignant in five. Of the five lesions yielding malignant features, four had invasive carcinoma and one had micropapillary ductal carcinoma in situ (DCIS). Surgery revealed invasive carcinoma in three of the cases interpreted as atypical papillary lesions and invasive cancer and micropapillary DCIS in three of the cases diagnosed as benign lesions. Similar results were obtained with CNB. DCIS was found in one out of six of the cases diagnosed as papilloma. Out of the four cases that were interpreted as atypical papillary lesion, surgery revealed invasive carcinoma in one case and one case had micropapillary DCIS. Diagnosis of malignancy was confirmed by histology in one case interpreted as papillary carcinoma by CNB. This study suggested that both FNAB and CNB share similar diagnostic challenges and a follow-up surgical excision is indicated when diagnosis of a papillary lesion is entertained by both procedures.     

Major histocompatibility complex status in breast carcinogenesis and relationship to apoptosis

Major histocompatibility complex (MHC) molecules are of central importance in regulating the immune response against tumors. In this study we used immunohistochemistry to study human leukocyte antigen (HLA) class I and II antigen expression in normal breast tissues and benign, preneoplastic, primary, and metastatic breast lesions using antibodies against beta-2-microglobulin (beta2-m), heavy-chain, and HLA-DR antigens. Whereas all normal tissues and benign lesions were positive for beta2-m and HLA-A, -B, and -C antigens, total loss of HLA class I antigens was found in 37% (11 of 30) of in situ carcinomas, in 43% (56 of 131) of the primary tumors, and in 70% (31 of 45) of the lymph node metastases. HLA-DR was also underexpressed in breast cancer cells; thus 20% (6 of 30) of in situ carcinomas, 15% of invasive carcinomas (20 of 131), and only 1 metastatic case were positive for this antigen. Both HLA class I and II antigen expression were more frequently down-regulated in metastatic lesions than in primary breast lesions (P <0.05), and a tendency toward a simultaneous defective expression of HLA class I and II antigens was observed in primary carcinomas (P = 0.07). However, no correlation was found between the expression of any of the aforementioned molecules and pathological parameters or survival. Interestingly, HLA class I expression was expressed more frequently in tissues with high apoptotic activity and was significantly associated with the expression of the proapoptotic bax gene (P = 0.02), and was inversely associated with expression of the antiapoptotic bcl-2 gene (P = 0.03). We conclude that alterations in HLA class I and II antigen expression are early events in breast carcinogenesis and play significant roles in metastatic progression. In addition, their expression is correlated with apoptosis-regulating proteins, which may influence the cytotoxicity of T cells against HLA class I-specific tumor antigens.     

Malignant giant cell tumor of synovium (malignant pigmented villonodular synovitis)

CONTEXT: Pigmented villonodular synovitis (PVNS) is a well-recognized entity that has the potential for extensive local destruction, even though it rarely metastasizes. Rare reports of malignant forms are recorded in the literature. We observed 2 patients in whom examples of PVNS followed an aggressive course with multiple recurrences, metastasis, or degeneration to an appearance resembling malignant fibrous histiocytoma. OBJECTIVE: We studied the occurrence and persistence of aneuploidy for chromosomes 5 and 7 in 2 patients with clinically aggressive PVNS. DESIGN: Fluorescence in situ hybridization was performed for the detection of chromosomes 5 and 7 in the primary lesions, recurrences, and metastases in 2 examples of PVNS. RESULTS: Fluorescence in situ hybridization demonstrated small but significant numbers of cells with trisomies for chromosomes 7 and/or 5 in both the primary and recurrent lesions of both patients. CONCLUSIONS: The presence of consistent chromosomal trisomies (5 and 7) in both patients' examples of PVNS suggests a neoplastic nature for this lesion. The persistence of these trisomies in the primary lesions, recurrences, and metastases supports a molecular link between the primaries, recurrences, and metastases despite changes in morphologic features. The presence of persistent trisomies in the recurrent and metastatic lesions supports the concept of malignant PVNS.     

Clinical,pathological and genetic features of women at high familial risk of breast cancer undergoing prophylactic mastectomy

Prophylactic mastectomy (PM) is a risk-management option for women at high familial risk of breast cancer (BC). This study describes the PM experience of women enrolled in a large observational cohort study involving families with a history of hereditary breast cancer. Within 357 multiple-case BC families [119 (33%) BRCA1 or BRCA2 mutation positive], identified via family cancer clinics, 49 cases of PM [21 (43%) BRCA1 or BRCA2 mutation positive] were identified and their clinical, pathological and genetic features reviewed. Families with at least one incidence of PM displayed stronger breast/ovarian cancer histories than did families without PM. Median age at time of PM was 45 years (range 28-58). Ten cases (21%) were bilateral PMs in unaffected women and 39 cases were contralateral PMs in women with prior invasive BC (71%) or ductal carcinoma in situ (DCIS) (8%). Most (88%) underwent total mastectomy. Unnecessary axillary surgery occurred in eight subjects (16%). Malignant histology was found in three PM specimens (6%). Prior to genetic testing, PM was performed in two women who were subsequently shown not to carry the mutation specific to their family. Optimal utilization of genetic testing to guide surgical decision making, appropriate surgical technique and careful pathology examination of PM specimens, are important issues to consider prior to PM in women at high familial risk of BC.     

Dedifferentiation and progression of an intracranial solitary fibrous tumor: autopsy case of a Japanese woman with a history of radiation therapy of the head during infancy

Solitary fibrous tumor (SFT) is usually an indolent neoplasm with a low rate of local recurrence and metastasis. Although dedifferentiation of low-grade sarcoma is well documented, the concept of dedifferentiated SFT was not recognized until recently. A case of intracranial SFT with seven recurrences within 5 years, showing progression and dedifferentiation during the course of disease, is reported here. A 51-year-old woman with a history of irradiation during infancy presented with a SFT in the right posterior fossa. Because of the close proximity to the brain stem, the tumor could not be removed completely. The tumor recurred 12, 16, and 28 months after the initial operation. With the repeated recurrences, cellularity, mitotic count, and Ki-67 (MIB-1) index increased gradually. The histology suddenly changed at the fourth recurrence, which occurred 16 months after postoperative radiation therapy for the third recurrence. The tumor revealed a fibrosarcoma-like appearance with necrosis and markedly increased mitotic activity. The tumor further recurred 50, 52, and 55 months after the initial operation with the same fibrosarcoma-like histology. The patient died of uncontrolled tumor 58 months after the initial operation. In this case radiation may have played some role in the tumorigenesis, progression, and dedifferentiation of the SFT.     

Can cytological findings predict intraductal spread of breast cancer? Histopathological case–control study

An important predictive factor for local recurrence after breast-conserving therapy is the state of the surgical margin. In order to obtain a negative surgical margin, the present case-control study was conducted to determine whether the extent of ductal spread can be estimated from the information obtained by fine-needle aspiration (FNA). Samples from 69 cases of extensive ductal spread (EDS) in which it was thought that cancer cells had remained in the residual breast when the lumpectomy was performed with 2 cm margins, were retrieved and compared with 62 cases having almost the same clinical and pathological tumor size. The cases of EDS included a significantly larger number of papillotubular carcinomas (37%vs 13%, P = 0.004) and displayed a high nuclear atypia (42%vs 26%, P = 0.001). We could estimate the same tendency with cytological studies. Cancer cells with cohesive papillary-like clusters suggesting papillotubular carcinoma and with a large nuclear diameter were significantly more numerous in cases of EDS (P < 0.01). In conclusion, EDS can be determined by estimating histological type via cytodiagnosis and measuring the nuclear diameter of cancer cells.     

An autopsy study of radial scar in the female breast

In a study of breasts from 83 consecutive, unselected female autopsies, 23 women (28%) were found to have radial scars. The lesion was multicentric in 67% and bilateral in 43%. The frequency of radial scar was significantly increased among women with fibrocystic disease (43%) compared to women without this lesion (17%). No difference in the frequency of radial scar was registered between women with primary breast malignancy and women with either normal breasts or benign breast abnormalities. No radial scar demonstrated transition to invasive or in situ carcinoma. No evidence was found of any association between radial scar and breast carcinoma.     

Needle core biopsy can reliably distinguish between benign and malignant papillary lesions of the breast

AIMS: To review 21 screen-detected papillary lesions in which the core biopsy findings suggested a papillary lesion and to correlate pathological and radiological findings in order to assess the risks of associated malignancy and the need for surgical intervention. The appropriate management of non-malignant papillary breast lesions detected on needle core biopsy (NCB) is currently uncertain. METHODS AND RESULTS: Forty-seven papillary breast lesions with a histological diagnosis of papilloma, papilloma with atypical ductal hyperplasia (ADH) or ductal carcinoma in situ (DCIS), multiple papillomas, 'papillomatosis' or papillary carcinoma (invasive or in situ) were identified from records at the Leeds Breast Screening and Assessment Unit. The cases were diagnosed between between May 1995 and May 2002. In 21 cases the previous NCB contained a papillary proliferation which had been categorized as either 'B2', benign, 'B3', of uncertain malignant potential, or 'B4', suspicious of malignancy. All of the 19 'B3' or 'B4' cases and one of the two 'B2' lesions had undergone open surgical biopsy. All cases with a previous 'B4' were malignant on subsequent excision. All excised cases with a previous 'B3' or 'B2' were found benign, although four of the 'B3's derived from papillomata associated with an atypical proliferation amounting to ADH. In three of these four (75%) the papillary proliferation had been associated with epithelial hyperplasia of usual type (HUT) on the core and the radiological features were of a mass lesion detected on incident round screen which had increased in size. CONCLUSION: Our results confirm the accuracy of NCB in the diagnosis of screen-detected papillary lesions of the breast. Surgical excision may not always be necessary following a 'B3' core biopsy.     

乳腺肿瘤手术治疗联合内镜腋窝淋巴结清扫的体会

目的评估乳腔镜辅助乳腺癌改良根治术同时进行腋窝淋巴结清扫治疗乳腺癌的疗效。方法对4例乳腺癌病例行保乳乳腺癌改良根治术．腋窝脂肪溶解抽吸后进行乳腔镜腋窝淋巴结清扫。结果全部患者均顺利完成手术，术中冷冻切片报告：标本切缘均无癌细咆残留，术后石蜡切片病理为乳腺浸润性导管癌4例。手术时间120～140rain，平均127．3min：手术出血量15～20m1，平均18．4ml；每侧取淋巴结10-13个，平均11个。术后病侧乳房形态保持良好，伤口小而隐蔽．手术效果满意。术后随访12～24个月，无瘤复发。结论在腔镜下行保乳乳腺癌切除术联合腋窝淋巴结清扫是安全可行的．具有常规手术无法达到的良好的美容效果。该术式对保护上肢功能、保持胸部良好的外观形状及提高患者的生存质量均是一种较好的手段．是治疗Ⅰ、Ⅱ期乳腺癌一种合理有效术式。     

Fine-needle aspiration of the breast: A review of 1,995 cases with emphasis on diagnostic pitfalls

Between 1985 to 1989, 1, 95 fine-needle aspirations of palpable breast lesions were performed at our institution. In all cases, the aspirates were procured by cytopathologists using 22- or 23-gauge needles. Direct smears were immediately stained with Diff-Quik and Papanicolaou and assessed for specimen adequacy (criteria as followed in this institution). Tissue follow-up was available in 1,117 cases. The cytologic diagnoses rendered in these cases were: malignant, 690 cases (60.2%); suspicious for carcinoma, 49 cases (4.3%); benign, 343 cases (29.9%), and insufficient specimen, 35 cases (3.1%). There were 28 false-negative and 2 false-positive results. Considering only cases definitively diagnosed as benign or malignant, the sensitivity was 96%, specificity 99%, positive predictive value 99%, negative predictive value 94%, and overall efficiency 97%. Of those specimens considered suspicious, only 11 cases (22%) were proved not to be malignant after excisional biopsy. These were three fibroadenomas, three ductal hyperplasias, two adenosis tumors, two mucocele-like lesions, and one nipple adenoma. The two lesions that resulted in true false-positive diagnoses were an apocrine cyst with atypia and sclerosing adenosis with radial scar. The clinical and cytologic features of the benign conditions that resulted in false suspicious and positive diagnoses and those features that distinguish them from carcinoma are presented.