GSTPi-positive tumour microenvironment-associated fibroblasts are significantly associated with GSTPi-negative cancer cells in paired cases of primary invasive breast cancer and axillary lymph node metastases.

BACKGROUND: Glutathione S-transferase Pi (GSTPi) expression is one of the factors, which is known to be associated with development of resistance to chemotherapeutics in cancer patients, including those with breast cancer. Yet, its expression has been reported to be undetectable in cancer cells in high percent of patients with primary breast cancer. However, GSTPi expression in stromal cells in breast tumour microenvironment, namely cancer-associated fibroblast (CAF), which is recognised to have major roles in cancer progression, remains poorly reported. METHODS: The aim of the study was to determine the expression of GSTPi; vimetin, a fibroblast-associated cytoskeleton protein; and α-smooth muscle actin (α-SMA), a known marker of CAF in breast cancer tissue, by immunohistochemical staining method in consecutive histologic sections of formalin-fixed and paraffin-embedded tissue biopsy specimens from a cohort of 39 paired cases of patients with invasive breast cancer and the corresponding axillary lymph nodes metastases. RESULTS: Ductal and acinar luminal epithelial cells, myoepithelial cells and surrounding fibroblasts exhibited a homogeneous cytoplasmic reactivity with anti-GSTPi antibody in 11 of 11 cases of benign breast tissue biopsies. The vimentin-positive fibroblasts were unreactive with anti-α-SMA antibody. Loss of GSTPi expression was observed in breast cancer cells, at both the primary and metastatic sites, in 31 of 39 paired cases, as compared with benign breast epithelial cells (Fisher's exact test P<0.001). A significant association was observed between GSTPi-positive, vimentin-positive and α-SMA-positive fibroblast in tumour microenvironment at both sites. CONCLUSION: This is an original report of demonstration of a significance association between tumour microenvironment-associated GSTPi-positive CAF (vimentin/α-SMA-positive) and the GSTPi-negative cancer cells in paired cases of primary invasive breast cancer and the corresponding axillary lymph nodes metastases.

Paget's disease of the breast: clinical, imaging and pathologic findings: a review of 16 patients.

OBJECTIVES: To determine the clinical, imaging and pathological findings of Paget's disease of the breast. MATERIALS AND METHODS: Approval by Institutional Review Board was granted and informed consent was waived. Retrospective review of the pathological diagnosis of 2,361 women with breast carcinoma between January 2004 and April 2010 revealed 27 patients with Paget's disease of the breast. The clinical, mammographic and ultrasonographic images were retrospectively reviewed. RESULTS: The prevalence of Paget's disease of the breast was 1.14% of all breast carcinoma at this institution. Of the 27 patients with Paget's disease, only 16 had imaging studies and this group constituted the basis of this study. All 16 patients were women, with ages ranging from 36-68 years (mean age 50.31 years). Eleven patients presented with clinical findings suggestive of Paget's disease of the breast. Seven of these 11 patients also had associated palpable mass(es). Four patients presented with a palpable mass alone and one presented with bloody nipple discharge alone. Mammography was performed in all 16 patients and ultrasonography (US) in 15 patients. Of the 16 mammographic studies, two were negative. Of the 15 US studies, three were negative. Of these three negative US studies, two also had negative mammography and one had pleomorphic microcalcifications on mammogram. US was helpful in detecting multifocality in two patients. Mammography was 100% positive in patients who presented with palpable breast mass(es) and bloody nipple discharge, but 50% positive in patients who had clinically suggestive Paget's disease alone. Almost all patients (15/16) had underlying breast malignancies. Seven patients had multifocality or multicentricity. Modified radical mastectomy was performed in 13 patients, simple mastectomy in two, and wide local excision in one patient. Pathological findings were ductal carcinoma in situ (DCIS) (n = 3), invasive ductal carcinoma (IDC) (n = 10), metaplastic carcinoma (n = 1), invasive lobular carcinoma (ILC) (n = 1), and only Paget's disease of the nipple without underlying breast carcinoma (n = 1). CONCLUSION: Patients with Paget's disease of the breast have a high incidence of an underlying breast carcinoma. Most of the patients in this study presented late and were more likely to have positive mammograms. Mammography should be performed to identify the underlying breast carcinoma. Those who have only nipple areolar changes and no palpable mass have less positive mammography and less invasive carcinoma.

Paget’s disease of the breast: clinical, imaging and pathologic findings: a review of 16 patients

Objectives: To determine the clinical, imaging and pathological findings of Paget’s disease of the breast. Materials and methods: Approval by Institutional Review Board was granted and informed consent was waived. Retrospective review of the pathological diagnosis of 2,361 women with breast carcinoma between January 2004 and April 2010 revealed 27 patients with Paget’s disease of the breast. The clinical, mammographic and ultrasonographic images were retrospectively reviewed. Results: The prevalence of Paget’s disease of the breast was 1.14% of all breast carcinoma at this institution. Of the 27 patients with Paget’s disease, only 16 had imaging studies and this group constituted the basis of this study. All 16 patients were women, with ages ranging from 36–68 years (mean age 50.31 years). Eleven patients presented with clinical findings suggestive of Paget’s disease of the breast. Seven of these 11 patients also had associated palpable mass(es). Four patients presented with a palpable mass alone and one presented with bloody nipple discharge alone. Mammography was performed in all 16 patients and ultrasonography (US) in 15 patients. Of the 16 mammographic studies, two were negative. Of the 15 US studies, three were negative. Of these three negative US studies, two also had negative mammography and one had pleomorphic microcalcifications on mammogram. US was helpful in detecting multifocality in two patients. Mammography was 100% positive in patients who presented with palpable breast mass(es) and bloody nipple discharge, but 50% positive in patients who had clinically suggestive Paget’s disease alone. Almost all patients (15/16) had underlying breast malignancies. Seven patients had multifocality or multicentricity. Modified radical mastectomy was performed in 13 patients, simple mastectomy in two, and wide local excision in one patient. Pathological findings were ductal carcinoma in situ (DCIS) (n = 3), invasive ductal carcinoma (IDC) (n = 10), metaplastic carcinoma (n = 1), invasive lobular carcinoma (ILC) (n = 1), and only Paget’s disease of the nipple without underlying breast carcinoma (n = 1). Conclusion: Patients with Paget’s disease of the breast have a high incidence of an underlying breast carcinoma. Most of the patients in this study presented late and were more likely to have positive mammograms. Mammography should be performed to identify the underlying breast carcinoma. Those who have only nipple areolar changes and no palpable mass have less positive mammography and less invasive carcinoma.

Fine needle aspiration cytology of papillary lesions of the breast: how accurate is the diagnosis?

BACKGROUND: Cytological diagnosis of mammary papillary lesions is difficult. AIM: To review the previous cytology diagnosis of 23 papillomas and 11 papillary carcinomas and specific cytological features that may assist in differentiating these entities. METHODS: The cytology preparations were reviewed for: (i) overall cellularity; (ii) epithelial cell ball devoid of fibrovascular cores; (iii) background single cells; and (iv) papillary fragments and their morphology. RESULTS: The overall diagnostic accuracy was 59%, atypical rate was 24%, and the error (combined false positive and negative) rate was 17%. For overall cellularity, 6, 14 and 3 cases of papillomas, and 6, 3 and 2 cases of papillary carcinomas showed low, moderate and high cellularity, respectively. Cell balls were present in mild to moderate number in 20 papillomas and 10 papillary carcinomas. The background single cells were absent, or present in low or moderate to high numbers in 7, 10 and 6 papillomas, and 3, 3 and 5 papillary carcinomas, respectively. Papillary fragments were absent, or present in small, moderate or large quantities in 9, 4, 8 and 2 papillomas, and 6, 3, 1 and 1 papillary carcinomas, respectively. There was no demonstrable quantitative difference between papilloma and papillary carcinoma for all these parameters. Qualitatively, the cell balls and single cells showed a higher degree of atypia in papillary carcinoma, and the papillary fragments were more elaborate and slender. CONCLUSION: Cytological diagnosis of papillary lesions shows a significant error rate with overlapping features. Cellular atypia and fragments with long and slender papillae with ramifying edges favour papillary carcinoma.

Benign breast lesions mimicking carcinoma at mammography.

Many benign breast lesions pose diagnostic challenges. These lesions include abscess, haematoma, radial scar, post surgical scar, diabetic mastopathy, focal fibrosis, sclerosing adenosis, granular cell tumour, extra-abdominal desmoid tumour, medial insertion of pectoralis muscle and sternalis muscle, and axillary lymphadenopathy (due to HIV infection, collagen vascular lesions, tuberculous and bacterial lymphadenitis). Radiologists should be familiar with the characteristic imaging features of these benign lesions, and should include these benign lesions in the differential diagnosis whenever malignant-appearing findings are encountered. Correlation of the patient's clinical features with the mammographical findings and additional use of ultrasonography, fine-needle aspiration biopsy or core biopsy are helpful in establishing the final diagnosis and obviating unnecessary surgical intervention. In some of these lesions, surgery may be avoided while in others, the appropriate surgical procedure may be planned. This pictorial essay aims to illustrate the mammographical features of these lesions in a group of proven cases.

Breast carcinomas: why are they missed?

INTRODUCTION: Mammography has proven to be an effective modality for the detection of early breast carcinoma. However, 4-34 percent of breast cancers may be missed at mammography. Delayed diagnosis of breast carcinoma results in an unfavourable prognosis. The objective of this study was to determine the causes and characteristics of breast carcinomas missed by mammography at our institution, with the aim of reducing the rate of missed carcinoma. METHODS: We reviewed the reports of 13,191 mammograms performed over a five-year period. Breast Imaging Reporting and Data Systems (BI-RADS) were used for the mammographical assessment, and reports were cross-referenced with the histological diagnosis of breast carcinoma. Causes of missed carcinomas were classified. RESULTS: Of 344 patients who had breast carcinoma and had mammograms done prior to surgery, 18 (5.2 percent) failed to be diagnosed by mammography. Of these, five were caused by dense breast parenchyma obscuring the lesions, 11 were due to perception and interpretation errors, and one each from unusual lesion characteristics and poor positioning. CONCLUSION: Several factors, including dense breast parenchyma obscuring a lesion, perception error, interpretation error, unusual lesion characteristics, and poor technique or positioning, are possible causes of missed breast cancers.

Metaplastic carcinoma of the breast: a clinicopathological review.

BACKGROUND: Mammary metaplastic carcinoma encompasses epithelial-only carcinoma (high-grade adenosquamous carcinoma or pure squamous cell carcinoma), biphasic epithelial and sarcomatoid carcinoma and monophasic spindle cell carcinoma. AIM: To evaluate the clinicopathological features of a large series of 34 metaplastic carcinomas. METHODS: 10 epithelial-only, 14 biphasic and 10 monophasic metaplastic carcinomas were assessed for nuclear grade, hormone receptor status, HER2/neu (cerbB2) oncogene expression, Ki-67 and p53, lymph node status and recurrence on follow-up. RESULTS: Intermediate to high nuclear grade were assessed in most (33/34) tumours. Oestrogen and progesterone receptors were negative in 8 of 10 epithelial-only, all 14 biphasic, and 9 of 10 monophasic tumours, cerbB2 was negative in 7 of 10 epithelial-only, all 14 biphasic and 8 of 10 monophasic tumours. Ki-67 was found to be positive in 6 of 10 epithelial-only, 6 of 14 biphasic, and 7 of 10 monophasic tumours, whereas p53 was positive in 6 of 10 epithelial-only, 7 of 14 biphasic, and 8 of 10 monophasic tumours. Lymph node metastases were seen in 7 of 7 epithelial-only, 7 of 11 biphasic, and 3 of 7 monophasic tumours. Recurrences were seen in 4 of 7 epithelial-only, 8 of 9 biphasic, and 4 of 9 monophasic tumours. CONCLUSIONS: All three subtypes of metaplastic carcinoma are known to behave aggressively, and should be differentiated from the low-grade fibromatosis-like metaplastic carcinoma, which does not metastasize. Oncological treatment options may be limited by the frequently negative status of hormonal receptor and cerbB2.

Atypical and suspicious categories in fine needle aspiration cytology of the breast: histological and mammographical correlation and clinical significance.

INTRODUCTION: This study aims to correlate fine-needle aspiration specimens diagnosed as C3 (atypical, probably benign) and C4 (suspicious, probably malignant) with histology and mammography, and to evaluate these two cytology categories in terms of diagnostic usefulness and patient management. METHODS: All fine-needle aspiration (FNA) specimens in categories C3 or C4 at the Maharaj Nakorn Chiang Mai Hospital, Thailand between 2000-2004 were reviewed. Results were correlated with available histological and mammographical studies. RESULTS: 148 FNA specimens were identified, comprising 43 category C3 and 105 category C4. Histology was available in 90 cases. 14 (64 percent) C3 cases showed benign histology on biopsy and eight (36 percent) were malignant. 13 (19 percent) C4 cases were benign on biopsy, whereas 55 (81 percent) were malignant. Mammographical studies were available in 56 of the histologically-proven cases. All seven cases with benign mammograms had benign histology, and all 26 cases called "highly suggestive of malignancy" were malignant on histology (five C3 and 21 C4). Of the 23 cases called "suspicious abnormality" on mammography, 14 turned out to be malignant on biopsy (one C3 and 13 C4). CONCLUSION: Our study supports maintaining cytology categories C3 and C4. About two-thirds of C3 cases were benign on biopsy whereas 81 percent of C4 cases were malignant (p-value is less than 0.001). There was complete correlation between histological and mammographical studies except those with equivocal mammograms. Our study supports the combined use of clinical, mammographical and cytological findings for optimal patient management. This is especially important for patients with C3 aspiration results, in order to avoid unnecessary surgery for benign lesions.

Painless scrotal swelling: ultrasonographical features with pathological correlation.

Scrotal swelling may be due to extratesticular and intratesticular lesions. The majority of extratesticular lesions are benign while the majority of intratesticular lesions are malignant. Ultrasonography (US) is helpful in separating extra- from intratesticular lesions. US can show whether a mass is cystic, solid or complex, and also features such as associated calcifications, epididymal involvement, scrotal skin thickening and colour Doppler flow pattern. Extratesticular lesions include hydrocoele, spermatocoele, varicocoele, epididymal cyst, hernia and tumours of the epididymis and cord structures. Intratesticular lesions include primary tumour, metastases, lymphoma and leukaemia. Tuberculous epididymitis or epididymo-orchitis may also present with painless scrotal swelling. US features of these disease patterns, with pathological correlation, are presented in this pictorial essay.

Role of mammography in diagnosis of axillary abnormalities in women with normal breast examination.

The mammograms of 43 patients presenting with palpable unilateral masses in the axilla and normal breasts on physical examination were retrospectively reviewed to determine the cause and imaging characteristics of axillary abnormalities, and the usefulness of mammography in detecting occult breast carcinoma. Cytological or histological confirmation was obtained in all patients. Forty of 43 patients had axillary lymphadenopathy while three had lipoma, fibroadenoma and haematoma, respectively. Causes of malignant lymphadenopathy (n = 22) were metastatic diseases from non-mammary primary malignancy (n = 8), occult ipsilateral breast carcinoma (n = 5), and previous contralateral breast carcinoma (n = 9). Causes of benign lymphadenopathy (n = 18) were reactive nodal hyperplasia (n = 6), collagen vascular diseases (n = 2), and acute bacterial (n = 2) and tuberculous (n = 8) lymphadenitis. Nodal size was not significantly different between benign and malignant lymph nodes. Benign and malignant nodal margins were variable. Intranodal microcalcifications were found in two cases of breast carcinoma metastasis. Intranodal macrocalcifications were found in three cases of tuberculous lymphadenitis. Occult primary breast carcinoma was detected on mammograms in four of five patients with axillary lymphadenopathy due to ipsilateral breast carcinoma. Mammographical features of benign and malignant lymphadenopathy may be indistinguishable, but presence of intranodal calcifications is helpful. Mammography is also valuable in depicting occult primary breast carcinoma.

Imaging of giant breast masses with pathological correlation.

Ultrasonography (US) and mammography are the two basic techniques for routine imaging in the diagnosis of breast diseases. A wide variety of breast conditions such as lipoma, hamartoma, cyst, fibroadenoma, phyllodes tumour, haematoma, abscess and carcinoma can result in solitary or multiple giant masses. These conditions may appear similar on physical examination. The clinical significance of these entities is that some lesions necessitate mastectomy but some lesions may require only local excision, aspiration or even conservative management. Imaging has enhanced our ability to characterise these lesions. The purpose of this pictorial review is to illustrate the causes of giant breast masses, and the role of US and mammography in diagnosis of these lesions.

Malignant germ cell tumours of undescended testes: imaging features with pathological correlation.

AIM: To illustrate the imaging features of malignant germ cell tumours complicating undescended testes, emphasizing the importance of recognizing this condition and providing a correct diagnosis to facilitate appropriate management. METHODS: The clinical presentation, ultrasonography (US) and computed tomography (CT) features of eight consecutive patients with malignant germ cell tumours of undescended testes were reviewed. RESULTS: CT performed in seven patients showed well-circumscribed soft-tissue masses with inhomogeneous enhancement in all cases. US in four patients showed circumscribed masses with inhomogeneous echogenicity. On pathological examination, there were two cases of embryonal carcinoma and six cases of seminoma. All tumours showed necrosis that correlated to inhomogeneous areas on imaging. CONCLUSION: The radiologist has an important role as he may be the first physician to suggest the diagnosis.

Breast cancer in women under 40 years: preoperative detection by mammography.

INTRODUCTION: This article assesses the diagnostic sensitivity of mammography in the preoperative detection of breast cancer in young women. MATERIALS AND METHODS: We retrospectively reviewed 1010 women with breast carcinoma between January 1996 and September 2002. The patients were identified from pathological reports. Of these, 237 women were below 40 years of age, accounting for 23.5% of all breast cancers. Only 76 of 237 patients had mammograms performed prior to surgery. Seventy-five of the 76 patients also had ultrasonography performed. Histological types were reviewed and the proportions of each type were compared with those found in a consecutive series of 773 breast carcinomas in women above 40 years of age seen during the same period in our hospital. The breast patterns, as seen on mammograms, were classified as follows: fatty, scattered fibroglandular, heterogeneously dense and homogeneously dense. Specific features of a mass, microcalcifications, architectural distortion and asymmetrical density were evaluated. RESULTS: Of the 76 patients who had mammograms performed prior to surgery, 81 cancers were found. The patients' age ranged from 25 to 40 years, with a mean of 36.4 years. The breast parenchymal patterns were homogeneously dense in 6.6%, heterogeneously dense in 67.1% and had scattered fibroglandular density in 26.3%. Abnormal mammographical findings were present in 93.8%. The most common mammographical findings were mass in 60% and microcalcifications, with or without associated breast abnormality, in 28.7%. The most frequent tumour (82.7%) was invasive ductal carcinoma, which is not significantly different to those found in older women (P = 0.895). Ultrasonography showed solid masses in 73 patients and was negative in the other 2 patients. CONCLUSION: Mammography is a useful imaging technique in providing preoperative detection and diagnosis of breast carcinoma in women below 40 years of age with clinical suspicion of malignancy. Mass and microcalcifications are the most common abnormal mammographical findings and invasive ductal carcinoma is the most common tumour found in our study.

Mammographic features of tuberculous axillary lymphadenitis.

The clinical and mammographic findings of 10 patients with pathologically proven tuberculous axillary lymphadenitis were reviewed. The cases were identified from 10 173 mammograms performed over 6 years at Maharaj Nakorn Chiang Mai University Hospital. The 10 patients were aged 31-65 years. All cases were initially diagnosed to have breast carcinoma with axillary nodal metastases. Eight patients presented with axillary swelling, while two presented with breast enlargement. None of these cases had a palpable breast mass. Associated supraclavicular, cervical or groin nodes were found in seven cases, and two patients had evidence of pulmonary tuberculosis. All lesions were unilateral, affecting the right side in eight cases and left side in two cases. On mammogram, the axillary nodes were enlarged and homogeneously dense. The nodes were sized 2.5-5 cm. Nodal margins were variable. Some nodes were matted. Macrocalcifications were noted in three cases. Ipsilateral breast oedema without mass or microcalcifications was present in two cases. Patients with tuberculous axillary lymphadenitis have large homogeneously dense nodes with either well- or ill-defined margins. It is impossible to differentiate tuberculous from malignant nodes. The presence of macrocalcifications might suggest tuberculous axillary lynphadenitis. Biopsy of enlarged axillary nodes is necessary to determine its aetiology.

Evaluation of the contralateral breast in patients with ipsilateral breast carcinoma: the role of mammography.

OBJECTIVE: To assess the value of mammography in the detection of cancer in the contralateral breast in women with ipsilateral breast carcinoma. MATERIALS AND METHODS: From February 1994 through May 2001, a total of 500 patients with unilateral mastectomy from breast carcinoma had mammograms performed for the first time following mastectomy. We retrospectively reviewed the clinical findings and mammograms of these patients. Four hundred and sixty-four patients were asymptomatic and 36 patients presented with palpable breast or axillary masses. Specific mammographic features of a mass, microcalcifications, architectural distortion and asymmetric density were evaluated. Diagnosis was confirmed by fine needle aspiration biopsy or surgical excision in all patients. RESULTS: Four hundred and sixty-four patients had screening mammograms and 36 patients had diagnostic mammograms. All 36 symptomatic patients had abnormal mammograms. Of these, 12 (33.33%) patients were found to have second primary breast carcinoma, 12 (33.33%) had metastases to the contralateral breast or axillary lymph nodes, six (16.66%) had fibroadenomas, two (5.55%) had abscesses, three (8.33%) had fibrocystic change, and one (2.77%) had axillary node reactive hyperplasia. Of the 464 asymptomatic patients, five (1.07%) had second primary breast carcinoma, five (1.07%) had fibrocystic change, and two (0.43%) had fibroadenomas. The mean age at the time of diagnosis of the first primary carcinoma in the symptomatic patients was 41.9 years (range 35-60 years), and was 43.4 years (range 36-56 years) in the screening group. The mean time interval between the two carcinomas was four years (range one to 13 years) in symptomatic group and 3.4 years (range one to four years) in screening group. The tumour stage in the screened group was in situ (n = 2), stage I (n = 3) and in the symptomatic group was stage I (n = 2), stage II (n = 5), stage III (n = 5). CONCLUSION: Patients who have ipsilateral breast carcinoma have a strong risk to develop a second primary carcinoma in the contralateral breast. Close follow-up of the second breast with careful clinical examination and mammography are necessary for the early detection of cancer.