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1.  The role of immunohistochemistry for smooth‐muscle actin, p63, CD10 and cytokeratin 14 in the differential diagnosis of papillary lesions of the breast 
Journal of Clinical Pathology  2006;60(3):315-320.
Background
Histological differentiation of mammary papillary lesions can be difficult. The evaluation of myoepithelial cells can be helpful, with benign papilloma showing a continuous myoepithelial cell layer, which becomes attenuated or absent in malignant papillary lesions.
Methods
A large series of 100 papillomas (28 papillomas with florid epithelial hyperplasia) and 68 papillary carcinomas (9 invasive, 44 in situ, and 15 ductal carcinomas in situ (DCIS) involving papillomas) of the breast were stained for myoepithelial cells by immunohistochemistry using antibodies to smooth‐muscle actin (SMA), p63, CD10 and cytokeratin (CK) 14.
Results
In the papillomas, using these four antibodies, myoepithelial cells were positive in 88%, 99%, 91% and 95% of cases, respectively, with SMA showing marked stromal component cell staining and CD10 showing epithelial and stromal staining. CK14 also showed epithelial staining in 71% of papillomas and 96% of papillomas with florid epithelial hyperplasia. In the papillary carcinomas, 36 (53%) cases showed staining of myoepithelial cells that were scattered, discontinuous and diminished in number and the remaining 32 (47%) cases did not show myoepithelial cells. Invasive papillary carcinoma has the lowest proportion (33%) with myoepithelial cells, and DCIS involving papillomas had the highest proportion (87%).
Conclusions
p63 had the highest sensitivity and did not cross‐react with stromal cells and only rarely with epithelial cells. CK14 has the added ability to distinguish between florid epithelial hyperplasia involving papilloma and DCIS involving papillomas. CK14 and p63 may be used as an adjunct in assessing difficult papillary lesions of the breast.
doi:10.1136/jcp.2006.036830
PMCID: PMC1860581  PMID: 16698948
2.  Intracystic papillary carcinoma of the breast in a 21-year old premenopausal Nigerian woman: a case report 
Rare Tumors  2009;1(2):e50.
We report the case of a 21-year-old Nigerian woman who presented to us with features of intracystic papillary carcinoma, a rare form of breast cancer usually seen in postmenopausal women in their sixth to eighth decades of life. To the best of our knowledge, there has been only one other case report of this lesion occurring in women in their second decade of life.
Physical examination showed a well-defined mass, 54 mm in diameter, in the upper proximal quadrant of the right breast close to the areola, histologically composed of monotypic epithelial cells disposed in solid, cystic, and papillary patterns. A diagnosis of intracystic papillary carcinoma was made because of the presence of intracystic arborization of the fibrovascular stroma, a monotonous cell population, the presence of mitoses, and the lack of myoepithelial cells determined by immunohistochemistry using calponin and p63 stains. Estrogen receptor status was positive while progesterone status and HER-2-neu receptor status were negative.
The patient has survived for 12 months without any sign of recurrence after the last surgical resection of the tumor.
doi:10.4081/rt.2009.e50
PMCID: PMC2994473  PMID: 21139929
intracystic papillary carcinoma; breast; young women.
3.  CD44s is useful in the differentiation of benign and malignant papillary lesions of the breast 
Journal of Clinical Pathology  2005;58(11):1185-1188.
Background/Aims: CD44s, the standard form of CD44, has been shown to be downregulated during malignant transformation of breast cancers. It has also been reported recently to be a useful marker in differentiating between benign and malignant papillary lesions of the breast, with high expression in the former. CD44s expression in benign and malignant papillary lesions was evaluated.
Methods: CD44s expression was assessed by immunohistochemistry in 101 benign papillomas and 59 papillary carcinomas (seven invasive papillary carcinomas, 41 papillary ductal carcinomas in situ, and 11 ductal carcinomas involving papillomas).
Results: Patients’ age and tumour size were significantly different between the papilloma and papillary carcinoma groups (p < 0.0001). CD44s showed positive staining in 45 papillomas (45%) and five papillary carcinomas (8%), and the difference was significant (p < 0.0001). The myoepithelial cells, when present, were also positive for CD44s in both groups, with no observable differences. Using CD44s positive staining to differentiate between benign and malignant papillary lesions gives a sensitivity, specificity, and accuracy of 45%, 92%, and 62%, respectively.
Conclusions: CD44s may be useful as an adjunct in the evaluation of morphologically problematic cases of papillary lesion of the breast.
doi:10.1136/jcp.2005.026906
PMCID: PMC1770758  PMID: 16254109
CD44; breast; papillary carcinoma; papilloma
4.  Papillary Carcinoma of the Breast in a Male Patient With a Treated Prostatic Carcinoma Diagnosed by Fine-Needle Aspiration Biopsy: A Case Report and Review of the Literature 
Diagnostic cytopathology  2006;34(3):214-217.
Papillary carcinoma of the male breast is very rare. In this case report, we describe the cytologic, histologic, immunohistochemical, and radiological findings of a papillary carcinoma of male breast. A 67-yr-old man, who had a previous history of prostatic adenocarcinoma, presented with a retroareolar painless mass. There was no known history of breast cancer in his family. A fine-needle aspiration biopsy (FNAB) was performed. Cytological examination revealed a cellular aspirate with three-dimensional papillary clusters. A diagnosis of papillary lesion favoring papillary carcinoma was rendered. Immunohistochemical staining of the cell-block of the FNAB revealed the presence of mammaglobin, and the absence of prostatic specific antigen. The patient underwent lumpectomy, which showed a moderately differentiated infiltrating papillary carcinoma with adjacent areas of ductal carcinoma in situ. FNAB is a useful technique in identifying male breast carcinoma. In conjunction with ancillary studies, this procedure can effectively differentiate between a primary versus metastatic lesion.
doi:10.1002/dc.20402
PMCID: PMC3428056  PMID: 16548002
male breast malignant tumor; papillary carcinoma; prostatic carcinoma; mammaglobin
5.  Intracystic papillary carcinoma associated with ductal carcinoma in situ in a male breast: a case report 
Cases Journal  2009;2:7260.
Introduction
Intracystic papillary carcinoma represents a small distinctive subgroup of noninvasive breast cancer, accounts for <0.5% of breast malignancies and is extremely rare in men, it was originally reported as a localized non-invasive carcinoma, but is usually associated with ductal carcinoma in situ around the main tumor or invasive carcinoma.
Case presentation
We report a case of 50-year-old man with intracystic papillary carcinoma in man with ductal carcinoma in situ who underwent a tumorectomy following by a radical Patey intervention (Halsted).
Conclusion
Nowadays, there is still no clear consensus regarding optimal treatment of intracystic papillary carcinoma. Most papers reinforce the importance of an adequate surgical margin in conservative treatment. Surgeons must pay much attention to the potential for ductal carcinoma in situ around the tumor when selecting the operative procedure.
doi:10.4076/1757-1626-2-7260
PMCID: PMC2740303  PMID: 19829939
6.  Intracystic Papillary Carcinoma of the Breast: Report of Three Cases and Literature Review 
Intracystic papillary carcinoma is a rare malignant tumor of the breast. It occurs communally in postmenopausal women. Clinically it can be asymptomatic or manifested by a breast mass or a nipple discharge. On imaging intracystic papillary carcinoma has usually benign features. Pathologic diagnosis can be difficult at classical histological examination and identification of myoepithelial cells layer by immunohistochemical study can be useful. In the majority of cases of pure intracystic papillary carcinoma, conservative management is possible. Adjuvant therapy is still controversial and prognosis is excellent. We report three cases of intracystic papillary carcinoma diagnosed on immunohistochemical examination and managed with conservative surgery.
doi:10.1155/2012/979563
PMCID: PMC3335648  PMID: 22567530
7.  Papillary squamous cell carcinoma of the mandibular gingiva 
Papillary squamous cell carcinoma (PSCC) has rarely been reported in the oral cavity. Herein reported is a case of PSCC in the mandibular gum. A 70-year-old man consulted our hospital because of a papillary tumor in the left mandibular gum. Physical examination revealed an exophytic papillary tumor of the left mandibular gum, and an excision of the tumor was performed. Grossly, the tumor was exophytic and papillary, and measured 1 x 1 x 0.8 cm. Microscopically, the tumor showed exophytic papillary proliferation with fibrovascular cores and consisted of atypical squamous epithelial cells. The tumor cells showed hyperchromasia, nuclear atypia, mitotic figures, apoptotic bodies, cancer pearls, and individual keratinization. Mild stromal invasion was seen. Immunohistochemically, the tumor cells were positive for pancytokeratin AE1/3, pancytokeratin CAM5.2, p63, p53, and Ki-67 (labeling index=40%), but negative for human papilloma virus (HPV). HPV in situ hybridization revealed no signals. Therefore, PSCC was diagnosed. The lateral and vertical margins are negative for tumor cell. The pathological diagnosis was PSCC. The patient was healthy and free from tumor three months after the operation.
PMCID: PMC3438768  PMID: 22977668
Papillary squamous cell carcinoma; oral cavity
8.  Metastatic breast carcinoma with appearance resembling micropapillary ductal carcinoma in situ. 
Journal of Clinical Pathology  1995;48(4):380-382.
AIM--To investigate tumour in an axillary lymph node resembling micropapillary ductal carcinoma in situ. METHODS--Sections of tumour in the breast and axillary lymph node were stained with haematoxylin and eosin, and immunohistochemically with antibodies to basement membrane and myoepithelial cells. RESULTS--Tumour in both the breast and axillary lymph node contained areas resembling micropapillary ductal carcinoma in situ. Surrounding these islands, there was a band of eosinophilic material resembling basement membrane and spindle cells that in places appeared to lie outside the basement membrane. Micropapillary tumour at both sites showed weak and discontinuous staining for collagen IV and laminin. The spindle cells stained for alpha-smooth muscle actin, but not for S100. By contrast, immunohistochemistry showed complete rings of basement membrane and myoepithelial cells around definite ductal carcinoma in situ and normal breast lobules and ducts. CONCLUSIONS--Invasive primary and metastatic carcinoma of the breast can have a growth pattern resembling micropapillary ductal carcinoma in situ.
Images
PMCID: PMC502561  PMID: 7615862
9.  Case Report: Ductal Carcinoma In Situ in the Male Breast 
Case Reports in Radiology  2012;2012:532527.
High-grade ductal carcinoma in situ is incredibly rare in male patients. The prognosis for ductal carcinoma in situ (DCIS) in a male patient is the same as it would be for a female with the same stage disease; therefore, early recognition and diagnosis are of the utmost importance. We present a case of a male with unilateral invasive ductal carcinoma who was diagnosed with DCIS in the contralateral breast. The DCIS presented as microcalcifications on mammography and was found to be biopsy proven grade 3 papillary DCIS. This case also illustrates the importance of family history and risk factors, all of which need to be evaluated in any male presenting with a breast mass or nipple discharge.
doi:10.1155/2012/532527
PMCID: PMC3463909  PMID: 23056988
10.  P-cadherin as a marker in the differential diagnosis of breast lesions 
Journal of Clinical Pathology  2003;56(2):139-141.
Aims: To assess the value of the calcium dependent cell adhesion molecule P-cadherin as a myoepithelial marker in the differential diagnosis of benign and malignant breast lesions.
Methods: Immunohistochemical analysis of normal breast, sclerotic breast lesions, tubular carcinomas, and ductal carcinoma in situ using a P-cadherin specific antibody and comparison with smooth muscle actin.
Results: All myoepithelial cells in normal breast ducts, ductules, and lobules and sclerotic lesions showed strong staining for P-cadherin. There was no staining of tubular carcinomas; myoepithelial cells were demonstrated around in situ carcinomas. Weaker reactivity was seen in a proportion of cells in some hyperplasias and in situ carcinomas. This weak reactivity in these tissues was not seen for smooth muscle actin but in radial scars, tubular carcinomas, and ductal carcinoma in situ staining of stromal cells caused difficulties in the identification of myoepithelial cells.
Conclusion: P-cadherin is a useful marker in the differential diagnosis of breast lesions.
PMCID: PMC1769891  PMID: 12560394
P-cadherin; breast disease; myoepithelial cell; immunohistochemistry
11.  Intracystic papillary carcinoma in a male as a rare presentation of breast cancer: a case report and literature review 
Introduction
The term "intracystic papillary ductal carcinoma in situ" has recently changed and is now more appropriately referred to "intracystic papillary carcinoma". Intracystic papillary carcinoma in men is an extremely rare disease with only a few case presentations published in the literature so far.
Case presentation
We discuss a case of a 44-year-old Caucasian man with an intracystic papillary carcinoma treated with simple mastectomy, sentinel lymph-node biopsy and contralateral risk-reducing mastectomy. These were followed by adjuvant radiotherapy of the breast.
Conclusion
Triple assessment (i.e. clinical examination and radiological and histological assessment) with a high level of clinical suspicion is necessary to diagnose intracystic papillary carcinoma in men due to its rarity. Furthermore, genetic testing and risk-reducing mastectomy should also be considered in cases of a strong family history for male breast cancer.
doi:10.1186/1752-1947-3-13
PMCID: PMC2635376  PMID: 19144122
12.  Immunostaining patterns of myoepithelial cells in breast lesions: a comparison of CD10 and smooth muscle myosin heavy chain 
Journal of Clinical Pathology  2004;57(6):625-629.
Background: Recent studies have reported CD10 expression in myoepithelial cells (MEC) of the breast, supporting its use as a marker to help distinguish invasive breast carcinoma (IC) from ductal carcinoma in situ (DCIS).
Aim: To compare the effectiveness of CD10 with smooth muscle myosin heavy chain (SMMHC) in the detection of MEC in benign and malignant breast lesions.
Methods: Histological material from 25 patients with DCIS and 21 with IC were immunostained for CD10 and SMMHC. Staining was scored on a scale of 0 to 3+ (0, no staining; 3+, intense) and the staining distribution was documented as focal, partial, or circumferential.
Results: Uniform, 3+ circumferential CD10 and SMMHC staining of MEC was seen in normal breast ducts and lobules, and in ducts and acini involved in sclerosing adenosis and apocrine metaplasia. In an analysis of total ducts involved by DCIS, 3+ circumferential staining was seen in 65 of 366 ducts (17.7%) stained for CD10 versus 190 of 396 ducts (48%) stained for SMMHC. MEC were not detected immunohistochemically in 116 of 366 ducts (31.7%) with anti-CD10 and 50 of 396 (12.7%) with anti-SMMHC. In contrast, all ICs were negative for both CD10 and SMMHC. Focal background staining of stromal myofibroblasts was seen with both CD10 and SMMHC, but CD10 showed a higher rate of non-specific staining of epithelial cells.
Conclusion: Although CD10 can aid in the distinction between IC and DCIS, SMMHC is a more sensitive and specific marker of MEC and shows less heterogeneity of immunostaining patterns.
doi:10.1136/jcp.2003.013227
PMCID: PMC1770324  PMID: 15166269
CD10; smooth muscle myosin heavy chain; myoepithelial cell
13.  Preferential Expression of MUC6 in Oncocytic and Pancreatobiliary Types of Intraductal Papillary Neoplasms Highlights a Pyloropancreatic Pathway, Distinct From the Intestinal Pathway, in Pancreatic Carcinogenesis 
The expression of different MUC glycoproteins has helped define cellular lineage in variety of pancreatic neoplasms, and has helped identify distinct carcinogenic pathways such as the intestinal pathway characterized by diffuse/strong MUC2/CDX2 expression in intestinal-type intraductal papillary mucinous neoplasms (IPMNs) and their associated colloid carcinomas (CCs). In this study, the expression profile of MUC6, a pyloric-type mucin, was investigated in both preinvasive and invasive pancreatic neoplasia. Florid papillary (“in-situ”) components of 9 intraductal oncocytic papillary neoplasms (IOPNs), 24 IPMNs, and 7 mucinous cystic neoplasms (MCNs), were analyzed immunohistochemically for MUC6 expression, as were 15 PanINs, 112 usual invasive ductal adenocarcinomas (DAs), and 14 CCs. In PanINs, MUC6 expression was limited to the very early areas of PanIN-1A that typically have pyloric features. Expression was lost in later stages. Similarly, in IOPNs or IPMNs or MCNs, MUC6 expression was detectable in the cystic or flat areas that have pyloric-like histology. However, in the more advanced (papillary) components of these neoplasms, MUC6 expression was mostly limited to the “cuboidal-cell” but was not seen in the “columnar-cell” phenotype: there was diffuse or strong expression in 8/9 IOPN and, relatively weaker but consistent expression in all 6/6 pancreatobiliary-type IPMNs; whereas virtually no expression in villous or intestinal-type IPMNs. The 7/8 gastric or foveolar-type IPMNs were also negative; in the single case with positivity, the labeling was limited to high-grade dysplastic areas. Interestingly, the papillae in MCNs were also mostly negative. Among invasive carcinomas, 39/112 DAs and only 1/14CC expressed MUC6. In DA, the expression did not correlate with survival (P=0.94), or any of the markers of aggressiveness: more than 2-cm tumor size (P=0.76), positive surgical margins (P=0.27), lymph node metastasis (P=0.82), or high grade (P=0.08). In conclusion: (1) The expression of MUC6 in oncocytic and pancreatobiliary-type neoplasms but not in villous or intestinal-type neoplasms supports the presence of a pyloropancreatic pathway distinct from the MUC2/CDX2 expressing intestinal pathway in intraductal papillary neoplasia. (2) MUC6 expression is present in the earliest (nonpapillary) form of any type of preinvasive neoplasia regardless of whether it is PanIN or IOPN or IPMN or MCN suggesting that these entities may share some characteristics early on, but evolve along divergent pathways as they progress.
doi:10.1097/PAS.0b013e3181cf8bb6
PMCID: PMC3160822  PMID: 20139757
MUC6; pancreas; intraductal; intraductal papillary mucinous neoplasm; mucinous cystic neoplasm; papilla; pyloric; intestinal
14.  “Intracystic papillary breast cancer: a clinical update” 
ecancermedicalscience  2013;7:286.
Introduction:
Intracystic (encysted) papillary cancer (IPC) is a rare entity of breast cancer accounting for approximately (1–2%) of all breast tumours [1], usually presenting in postmenopausal women and having an elusive natural history. The prediction of the biological behaviour of this rare form of breast cancer and the clinical outcome showed its overall favourable prognosis; however, its consideration as a form of ductal carcinoma in situ with non-invasive nature is to be reconsidered as it has been shown to present histologically with invasion of basement membrane and even metastasis [2]. The objective of this review is to shed some light on this rare, diagnostically challenging form of breast cancer, including its radiological, histological, and molecular characteristics and its pathological classification. The final goal is to optimize the clinical management including the role of sentinel lymph node biopsy (SLNB), general management with adjuvant radiotherapy (RT), mammary ductoscopy, and hormonal treatment.
Methods:
A literature review, facilitated by Medline, PubMed, and the Cochrane database, was carried out using the terms ‘Intracystic (encysted) papillary breast cancer’.
Results:
Intracystic papillary breast cancer (IPC) is best managed in the context of a multidisciplinary team. Surgical excision of the lump with margins in excess of 2 mm is considered satisfactory. Sentinel lymph node biopsy (SLNB) is recommended as data have shown the possibility of the presence of invasive cancer in the final histology. RT following IPC alone is of uncertain significance as this form of cancer is usually low grade and rarely recurs. However, if it is associated with DCIS or invasive cancer and found in young women, radiotherapy may be prudent to reduce local recurrence. Large tumours, centrally located or in cases where breast conserving surgery is unable to achieve a favourable aesthetic result, a skin sparing mastectomy with the opportunity for immediate reconstruction can be offered. Adjuvant endocrine therapy may be suggested as almost certainly these tumours are hormonal positive.
Conclusion:
Further research is required to determine the role of adjuvant radiotherapy and endocrine therapy in IPC. Understanding the low-grade nature of this form of breast cancer allows treatment options to be less radical and safely omitted.
doi:10.3332/ecancer.2013.286
PMCID: PMC3539854  PMID: 23304242
intracystic papillary breast cancer; wide local excision; ductal carcinoma in situ; mammary ductoscopy; sentinel lymph node biopsy; radiotherapy; endocrine therapy; local recurrence
15.  Pleomorphic Lobular Carcinoma in a Male Breast: A Rare Occurrence 
Carcinoma of male breast is uncommon as it accounts for 0.7% of total breast cancer. The pathology of male breast cancer is remarkably similar to that of cancers seen in women. The same histological subtypes of invasive cancer are present, although papillary carcinomas (both invasive and in situ) are more common and lobular carcinomas are less common. The predominant histological type, in males, as in females, reported in large series has been infiltrating ductal carcinoma with scattered reports of infiltrating lobular carcinoma, all of them of classical type except for a single case of pleomorphic infiltrating lobular carcinoma. Herein, we describe a case of pleomorphic lobular carcinoma occurring in male breast.
doi:10.4061/2010/871369
PMCID: PMC2995908  PMID: 21151643
16.  Papillary squamous cell carcinoma of the oral cavity with acantholytic and pseudovascular features 
Herein reported is a case of papillary squamous cell carcinoma (PSCC) in the oral cavity with features of koilocytosis, acantholysis and pseudovascular structure. A 73-year-old woman consulted to our hospital because of a tumor in the right mandibular gum. Physical examination revealed an exophytic papillary tumor of the right mandibu-lar gum, and a biopsy was performed. The biopsy revealed squamous cell carcinoma. No metastases were found by various imaging techniques. Therefore, resection of the tumor and mandibular bone was performed. Grossly, the tumor was exophytic and papillary, and measured 2 × 2 × 1 cm. The mandibular bone was free from tumor invasion. Microscopically, the tumor showed exophytic papillary proliferation with fibrovascular cores and consisted of atypical squamous epithelial cells. The tumor cells showed hyperchromasia, nuclear atypia, mitotic figures, apoptotic bodies, cancer pearls, and individual keratinization. Mild stromal invasion was seen. Therefore, PSCC was diagnosed. Koilocytosis, acantholytic features, and pseudovascular features were recognized in some areas. The lateral and vertical margins are negative for tumor cells. The mandibular bone was negative for tumor invasion. The pathological diagnosis was PSCC with koilocytotic, acantholytic and pseudovascular features. The patient was healthy and free from tumor three months after the operation.
PMCID: PMC3225792  PMID: 22135728
Papillary squamous cell carcinoma; oral cavity
17.  Pancreatic trypsinogen and cathepsin B in human pancreatic carcinomas and associated metastatic lesions. 
British Journal of Cancer  1994;69(1):152-156.
Expression of pancreatic trypsinogen and cathepsin B in 23 surgically resected pancreatic ductal adenocarcinomas was evaluated immunohistochemically, using a monoclonal antibody against human pancreatic trypsinogen and a polyclonal antibody against human cathepsin B. Fifteen of 20 invasive tubular adenocarcinomas (75%) expressed pancreatic trypsinogen in a coarse granular pattern located in the supranuclear cytoplasm of the carcinoma cells. In addition, metastatic lesions, including those in peripancreatic lymph nodes and neural plexuses, expressed pancreatic trypsinogen. In contrast, three intraductal (non-invasive) papillary adenocarcinomas did not express pancreatic trypsinogen. Cathepsin B expression was recognised in 14 of 20 invasive tubular adenocarcinomas (70%) in a fine granular pattern located diffusely in the cytoplasm of the carcinoma cells, while none of the three intraductal papillary adenocarcinomas had detectable cathepsin B. These findings suggest that pancreatic invasive ductal adenocarcinomas express pancreatic trypsinogen and cathepsin B immunoreactive peptides, raising the possibility that pancreatic trypsinogen and cathepsin B may act independently of each other in the process of carcinoma invasion and metastasis, like other different classes of proteases involved in the proteolytic modification of the matrix barrier.
Images
PMCID: PMC1968761  PMID: 8286198
18.  Intraductal papilloma of ectopic breast tissue in axillary lymph node of a patient with a previous intraductal papilloma of ipsilateral breast: a case report and review of the literature 
Diagnostic Pathology  2010;5:17.
The presence of ectopic breast tissue in axillary lymph nodes (ALN) is a benign condition that must be differentiated from primary or metastatic carcinoma. Here we report a patient who underwent excision of enlarged ALN 10 years after she had received surgical treatment of ipsilateral breast for an intracystic intraductal papilloma (IDP). Histological examination of the removed ALN revealed that the proliferative lesion consisted of papillary and tubular structures lined by luminal cuboidal cells and a distinct outer layer of myoepithelial cells resembling IDP of the breast. Immunostaining with a set of immunohistochemical markers including AE/AE3, alpha-smooth muscle actin and p63 in combination with estrogen and progesterone receptors confirmed the diagnosis of ectopic IDP.
This case shows that even though benign proliferative change in ectopic breast tissue is an extremely rare phenomenon, this possibility should be taken into account for correct diagnosis.
doi:10.1186/1746-1596-5-17
PMCID: PMC2841131  PMID: 20222992
19.  Distribution of ferritin, transferrin and lactoferrin in breast carcinoma tissue. 
Journal of Clinical Pathology  1984;37(1):51-55.
An immunoperoxidase staining technique was used for detecting three major iron binding proteins (ferritin, transferrin and lactoferrin) in 40 breast carcinoma cases and six benign breast proliferative lesions. Ferritin staining was detected mainly in connectival stroma and in histiocytes surrounding neoplastic cells. Few and faint ferritin positivities were also detected in neoplastic cells of 20 carcinoma cases. Transferrin was found inconsistently in myoepithelial cells surrounding normal ductules, or around neoplastic ducts of ductal in situ carcinoma. In eight carcinoma cases, transferrin staining was also positive in neoplastic cells. Lactoferrin was detected only in normal breast epithelial cells and in benign breast proliferative lesions. These immunohistochemical findings may suggest that raised serum ferritin concentrations in breast carcinoma patients might be attributed to stromal reaction rather than to tumour synthesis. Transferrin staining of neoplastic cells in these carcinoma cases appears to be very intriguing, particularly since transferrin is considered an obligate requirement for growing cells, and transferrin receptors have been demonstrated only in dividing cells. On the basis of the immunohistochemical data, lactoferrin might be used as a pointer to benign lesions.
Images
PMCID: PMC498617  PMID: 6323544
20.  D2-40: an additional marker for myoepithelial cells of breast and the precaution in interpreting tumor lymphovascular invasion 
D2-40 is a recently available mouse monoclonal antibody specific for human podoplanin and has been used in identifying lymphovascular invasion (LVI) of tumors. Although its expression has been evaluated in other tissues, its use as a marker for myoepithelial cells (MEC) of breast has not been studied. To explore its expression in the MEC of breast, paraffin-embedded tissue blocks from 48 patients with breast diseases were selected to include usual ductal hyperplasia (UDH, 41 cases), atypical ductal hyperplasia (ADH, 4 cases) and ductal carcinoma in situ (DCIS, 17 cases). Normal breast parenchyma and invasive carcinoma coexisting in the tissue sections were also included in the study. Immunohistochemistry for D2-40, calponin and p63 was performed and the staining patterns were reviewed and compared. D2-40 immunohistochemical staining is positive in the cytoplasm of MEC in UDH, ADH, and the majority of DCIS. The staining pattern of D2-40 is comparable with that of calponin, however D2-40 staining of MEC is weaker than that of calponin and with less background. In addition, myoepithelial cells and myofibroblasts at the edge of retraction spaces of DCIS are also stained by D2-40 that could be misinterpreted as tumor LVI. In conclusion, D2-40 immunohistochemistry reliably identifies the MEC of breast in a variety of lesions in a pattern similar to that of calponin and p63, and can be used as an additional MEC marker. Caution should be exercised when interpreting the staining of cells surrounding DCIS and carcinoma with retraction artifact.
PMCID: PMC3037204  PMID: 21326813
D2-40; myoepithelial cells; breast; lymphovascular invasion
21.  Clinical characteristics of different histologic types of breast cancer 
British Journal of Cancer  2005;93(9):1046-1052.
Breast cancer is a heterogeneous disease, though little is known about some of its rarer forms, including certain histologic types. Using Surveillance, Epidemiology, and End Results Program data on 135 157 invasive breast cancer cases diagnosed from 1992 to 2001, relationships between nine histologic types of breast cancer and various tumour characteristics were assessed. Among women aged 50–89 years at diagnosis, lobular and ductal/lobular carcinoma cases were more likely to be diagnosed with stage III/IV, ⩾5.0 cm, and node-positive tumours compared to ductal carcinoma cases. Mucinous, comedo, tubular, and medullary carcinomas were less likely to present at an advanced stage. Lobular, ductal/lobular, mucinous, tubular, and papillary carcinomas were less likely, and comedo, medullary, and inflammatory carcinomas were more likely to be oestrogen receptor (ER) negative/progesterone receptor (PR) negative and high grade (notably, 68.2% of medullary carcinomas were ER−/PR− vs 19.3% of ductal carcinomas). In general, similar differences were observed among women diagnosed at age 30–49 years. Inflammatory carcinomas are associated with more aggressive tumour phenotypes, and mucinous, tubular, and papillary tumours are associated with less aggressive phenotypes. The histologic types of breast cancer studied here differ greatly in their clinical presentations, and the differences in their hormone receptor profiles and grades point to their likely different aetiologies.
doi:10.1038/sj.bjc.6602787
PMCID: PMC2361680  PMID: 16175185
breast carcinoma; histology; SEER; stage; oestrogen receptor
22.  Non-receptor Tyrosine Kinase 2 Reaches its Lowest Expression Levels in Human Breast Cancer during Regional Nodal Metastasis 
Almost half of breast Ductal Carcinoma in situ are likely to remain non threatening in situ lesions with no invasion to the surrounding stroma and no metastases. The majority of focal disruptions in myoepithelial (ME) cell layers indicative of invasion onset were found to be overlying epithelial cell clusters with no or substantially reduced estrogen receptor α (ERα) expression. Here we report the down-regulation of Tyrosine kinase-2 (TYK2) and up-regulation of Strumpellin expression, among other proteins in ERα(−) cells located at disrupted ME layers compared to adjacent ERα(+) cells overlying an intact myoepithelial layer. ERα(+) and ERα(−) cells were microdissected from the same in vivo human breast cancer tissues, proteins were extracted and separated utilizing Differential in-Gel Electrophoresis (DIGE) followed by trypsin digestion, MALDI-TOF analysis, and protein identification. Proteins expressed by ERα(−) cell clusters were found to express higher levels of strumpellin that binds to Valosin-containing protein (VCP) to slow-down wound closure and promote growth; and lower levels of TYK2, a jak protein necessary for lineage specific differentiation. TYK2 levels were further analyzed by immunohistochemistry (IHC) in a cohort composed of 70 patients with broad clinical characteristics. TYK2 levels were minimal in TxN1M0 breast cancers which is the stage where the initial regional lymph node metastasis is observed. Our data highlight the role of TYK2 downregulation in breast cancer cell de-differentitation and initiation of regional metastasis. In addition, the aggressiveness of the ERα(−) cell clusters compared to ERα(+) ones present in the same duct of the same patient was confirmed.
doi:10.1007/s10585-011-9437-1
PMCID: PMC3449303  PMID: 22116632
DCIS; Estrogen receptor α; Proteomics; Tissue microdissection; TYK2
23.  Medullary and papillary carcinoma of the thyroid gland occurring as a collision tumor with lymph node metastasis: A case report 
Introduction
Papillary thyroid carcinoma and medullary thyroid carcinoma are two different thyroid neoplasia. The simultaneous occurrence of medullary thyroid carcinoma and papillary thyroid carcinoma as a collison tumor with metastases from both lesions in the regional lymph nodes is a rare phenomenon.
Case presentation
A 32-year-old Iranian man presented with a fixed anterior neck mass. Ultrasonography revealed two separate thyroid nodules as well as a suspicious neck mass that appeared to be a metastatic lesion. The results of thyroid function tests were normal, but the preoperative calcitonin serum value was elevated. Our patient underwent a total thyroidectomy with neck exploration. Two separate and ill-defined solid lesions grossly in the right lobe were noticed. Histological and immunohistochemical studies of these lesions suggested the presence of medullary thyroid carcinoma and papillary thyroid carcinoma. The lymph nodes isolated from a neck dissection specimen showed metastases from both lesions.
Conclusions
The concomitant occurrence of papillary thyroid carcinoma and medullary thyroid carcinoma and the exact diagnosis of this uncommon event are important. The treatment strategy should be reconsidered in such cases, and genetic screening to exclude multiple endocrine neoplasia 2 syndromes should be performed. For papillary thyroid carcinoma, radioiodine therapy and thyroid-stimulating hormone suppressive therapy are performed. However, the treatment of medullary thyroid carcinoma is mostly radical surgery with no effective adjuvant therapy.
doi:10.1186/1752-1947-5-590
PMCID: PMC3284582  PMID: 22185367
24.  Intracystic Papillary Carcinoma of the Breast in a Male Patient: A Case Report 
Case Reports in Medicine  2012;2012:378157.
Breast carcinoma is an uncommon neoplastic condition among man, accounting for not more than 1% of all breast cancers. Intracystic papillary carcinoma in man is an extremely rare condition and represents only 5–7,5% of all male breast carcinomas. Clinical and radiological manifestations of intracystic papillary carcinomas are not specific. Pathologic diagnosis can be difficult at classical histological examination and identification of myoepithelial cells layer by immunohistochemical study can be useful. Adjuvant therapy is still controversial and prognosis is excellent. We report a case of this rare histological type of breast cancer in 48-year-old male patient and review the literature.
doi:10.1155/2012/378157
PMCID: PMC3509421  PMID: 23251172
25.  Primary myoepithelial carcinoma of palate 
Objectives
The aim of this study was to present a rare neoplasm, Primary myoepithelial carcinoma arising from the palate, and to review its diagnostic criteria, pathologic and clinical characteristics, treatment options and prognosis.
Clinical Presentation and Intervention
Myoepitheliomas are tumors arising from myoepithelial cells mainly or exclusively. Myoepitheliomas mostly occur in salivary glands, as well as in breast, skin, and lung. Case of myoepitheliomas in palate has rarely been reported. Myoepithelial carcinoma is malignant counterpart of myoepitheliomas. Adenomyoepithelioma is also a different disease from myoepitheliaomas. Immunohistochemically, tumor cells of myoepithelial carcinoma express not only epithelial markers such as cytokeratin, epithelial membrane antigen (EMA), but also markers of smooth muscle origin such as calponin. The immunohistochemical criteria of myoepithelial differentiation are double positive for both cytokeratins and one or more myoepithelial immunomarkers (i.e., S-100 protein, calponin, p63, GFAP, maspin, and actins). Myoepithelial carcinomas of salivary and breast demonstrate copy number gains and gene deletion. The overall prognosis of myoepithelial carcinoma is poor. There is rarely recurrence or metastasis in benign myoepithelial tumors. Complete excision with tumor-free margin is always the preferred treatment, while local radiation therapy and chemotherapy are suggestive treatment options. Here, a rare case of myoepithelial carcinoma arising from the palate has been described and discussed for the treatment and outcome. Pathological and clinical characters of myoepitheliomas are also compared and discussed.
Conclusion
The case report serves to increase awareness and improve the index of diagnosis and treatment of myoepitheliomas.
doi:10.1186/1477-7819-9-104
PMCID: PMC3184273  PMID: 21917131
Myoepithelial carcinoma; Palate; Myoepitheliomas

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