Invasive ductal carcinoma of the breast with signet-ring cell and mucinous carcinoma components: diagnostic utility of immunocytochemistry of signet-ring cells in aspiration cytology materials

Breast cancer with signet-ring cells is very rare. In this article, we present a case of invasive ductal carcinoma with signet-ring cells and mucinous carcinoma components, which could be diagnosed as a primary cancer by immunocytochemical study of fine-needle aspiration cytology material. A 73-yr-old Japanese woman noticed a palpable mass in the left breast. The aspiration cytology disclosed the monotonous proliferation of signet-ring cell with cytological atypia. The immunocytochemical examination of neoplastic cells showed a positive reaction for estrogen receptor. The extensive examination of body before the operation did not disclose any tumors in other anatomic sites. The histological examination of surgically resected breast tumor showed invasive ductal carcinoma with foci of signet-ring cell and mucinous carcinomas. Finally, our preliminary report suggests that immunocytochemical examination of aspiration cytology materials may provide useful information in searching the primary site of breast carcinoma with signet-ring cells.     

Basaloid type adenoid cystic carcinoma of the breast.

We report a case of adenoid cystic carcinoma (ACC) of the breast with a prominent basaloid feature. The patient was a 62-year-old Japanese woman with a right breast mass, measuring 1.5 cm in diameter. Histologically, the tumor was composed of basal cell-like tumor cells, and it was originally diagnosed as invasive ductal carcinoma. The presence of PAS-positive basement membrane material around the tumor cell nests may be a diagnostic clue to ACC. The prognosis of ACC of the breast is considered to be favorable. However, basaloid type ACC may represent a poor prognosis, since our case revealed an aggressive behavior in spite of its small size.     

Metaplastic breast carcinoma with melanocytic differentiation

Metaplastic carcinoma of the breast is a rare heterogeneous malignancy, accounting for <1% of all invasive breast carcinomas, in which adenocarcinoma is found to coexist with an admixture of spindle, squamous, chondroid or bone-forming neoplastic cells. Metaplastic breast carcinoma composed of both epithelial and melanocytic elements is rare, and only seven cases have been reported so far. Reported herein is the case of a 38-year-old woman with a nodular mass in her left breast suspicious of malignancy, discovered during routine ultrasound examination. After histological and immunohistochemical examination of the resected tumor mass, initial diagnosis was collision tumor: ductal invasive carcinoma and metastatic melanoma. The patient underwent quadrantectomy, chemotherapy and radiotherapy. At 6 years follow up the patient was alive and healthy, without local recurrence or metastases. After revising slides and the literature, in addition to patient follow up, it was concluded that this case represents metaplastic carcinoma with melanocytic differentiation.     

Distribution of laminin,type IV collagen and fibronectin in the invasive component of breast carcinoma

Laminin, type IV collagen and fibronectin were examined immunohistochemically in the invasive component of breast carcinomas. Laminin was expressed around the invasive carcinoma cell nests in 38 (54%) of 71 cases. Immunoreactiv-ity for type IV collagen was observed around the invasive carcinoma cell nests or the stroma apart from carcinoma cells in 44 (80%) of 55 cases. Fibronectin was strongly expressed in the stroma only in 75 (99%) of 76 cases. The expression of laminin significantly correlated with tubular formation in the invasive carcinoma cell nests and showed a tendency to be correlative to estrogen receptor (ER) and progesterone receptor (PgR) of carcinoma tissue, but no correlation among laminin expression, histological type, the age of patients, tumor size and lymph node metastasis was noted. Type IV collagen and fibronectin did not correlate to any clinicopathological factors such as histological type, grade of differentiation, the age of patients, tumor size, lymph node metastasis, ER and PgR status. No concordant expression of these extracellular matrices was seen.     

43例食管基底样鳞状细胞癌临床病理分析

目的探讨食管基底样鳞状细胞癌（basaloid squamous cell carcinoma,BSCC）临床病理特点。方法对43例食管BSCC进行组织形态学及免疫组化观察,并对其临床病理特点及随访资料进行分析。结果BSCC由类似于鳞状上皮基底细胞样的细胞组成,细胞排列呈实性巢状、小梁状、假腺样或筛状结构,巢周边瘤细胞常呈栅栏状排列,巢中央可见粉刺样坏死。24例（55.8％）与普通鳞癌或腺鳞癌并存,11例（25.6％）出现局灶鳞化,28例（65．1％）见到脉管内癌栓。免疫组化染色CKpan、AE1、AE3均呈不同程度的阳性表达,p53、Ki-67、PCNA呈中至强阳性表达,Syn、CgA分别有1例呈弱阳性,S-100蛋白、SMA、CEA均为阴性。结论BSCC是食管一种少见的鳞状细胞癌变异型,具有独特的形态特点和明显的侵袭性行为,预后较差。免疫组化无特异性,诊断主要依靠形态学特点。     

Breast carcinoma with predominant neuroendocrine differentiation

Neuroendocrine differentiation can be identified in a subset of human breast carcinomas, either as scattered cells or as a predominant neuroendocrine component. We report a case of an invasive breast carcinoma largely composed of neuroendocrine cells. Eight years after a left mammary lumpectomy for a pT2N1MO SBR III invasive ductal carcinoma, a 67-years-old woman presented with a metastastic neuroendocrine sternal mass. To establish a relationship between mammary carcinoma and bone metastasis, histological slides of both the breast tumor and axillary lymph nodes were reviewed, and an immunohistochemical study was performed. They showed that: a) the mammary carcinoma was composed of a majority of small and large neuroendocrine cells synaptophysin +, NCAM+, chromogranin - (80%), associated with 2 other differentiated non endocrine components, one of metaplastic squamous carcinoma (10%) and the other of ductal carcinoma (10%); b) 4 axillary lymph nodes were involved by the ductal component which contained few NCAM + but synaptophysin - cells; c) Estrogen and progesterone receptors and HER2 were negative in the breast tumor and the metastatic nodes. We discuss the histogenesis of composite mammary carcinomas with neuroendocrine differentiation, the outcome of each component and the prognostic relevance of such a diagnosis.     

A case of extensively spreading acinic cell carcinoma of the breast with microglandular features

Acinic cell carcinoma (ACC) is an exceptionally rare type of breast carcinoma with a low-grade morphology and a favorable prognosis. It is postulated to be a type of invasive carcinoma arising in microglandular adenosis (MGA). We report a case of extensively spreading ACC of the breast with MGA-like features. Macroscopically, yellowish nodules were widely distributed throughout the right breast, up to the axilla, without mass formation. Microscopically, the tumor consisted of two distinct carcinoma components: one was multiple nodular lesions showing invasive carcinoma with fused solid nests, and the other was a widely spreading lesion exhibiting MGA-like features with uniform small single glands. Immunohistochemically, both components were negative for ER, PR, and HER2, and expressed EMA, S100 and lysozyme. The distinct morphology and molecular expression indicated ACC. The single glands in the MGA-like area lacked myoepithelial cells but were linearly surrounded by type IV collagen, a basement membrane component. This case supports the hypothesis that ACC and MGA have the same lineage and indicates that ACC is not necessarily a low-grade malignancy and can be aggressive.     

乳头部腺瘤的临床病理观察

目的 探讨乳头部腺瘤的临床病理形态学及免疫表型特点、诊断及鉴别诊断.方法 应用光镜观察、免疫组织化学EnVision两步法等对18例乳头部腺瘤进行分析,并复习文献.结果 肿瘤局限于乳头或乳晕下,多数与表皮相连,主要由扩张的导管与纤维化间质组成,腺上皮不同程度增生,多数为复层或有实性巢状、筛状、乳头状或微乳头状等复杂结构,细胞杂乱、拥挤、重叠,导管周围存在完整肌上皮;有时间质明显纤维化、硬化.免疫组织化学染色显示34βE12上皮阳性,CK5/6上皮与肌上皮片状阳性,p53和c-erbB-2阴性,p63、平滑肌肌动蛋白、Calponin等染色显示导管周围存在完整肌上皮.结论 乳头部腺瘤是少见的良性肿瘤,常表现为硬化性乳头状瘤病、乳头状瘤病型腺病或旺炽型硬化性腺病等形态,易与导管上皮不典型增生/导管内癌、浸润性导管癌、低度恶性腺鳞癌等混淆;应密切结合肿瘤部位及形态学,辅之以免疫组织化学诊断.     

乳头部腺瘤的临床病理观察

目的 探讨乳头部腺瘤的临床病理形态学及免疫表型特点、诊断及鉴别诊断.方法 应用光镜观察、免疫组织化学EnVision两步法等对18例乳头部腺瘤进行分析,并复习文献.结果 肿瘤局限于乳头或乳晕下,多数与表皮相连,主要由扩张的导管与纤维化间质组成,腺上皮不同程度增生,多数为复层或有实性巢状、筛状、乳头状或微乳头状等复杂结构,细胞杂乱、拥挤、重叠,导管周围存在完整肌上皮;有时间质明显纤维化、硬化.免疫组织化学染色显示34βE12上皮阳性,CK5/6上皮与肌上皮片状阳性,p53和c-erbB-2阴性,p63、平滑肌肌动蛋白、Calponin等染色显示导管周围存在完整肌上皮.结论 乳头部腺瘤是少见的良性肿瘤,常表现为硬化性乳头状瘤病、乳头状瘤病型腺病或旺炽型硬化性腺病等形态,易与导管上皮不典型增生/导管内癌、浸润性导管癌、低度恶性腺鳞癌等混淆;应密切结合肿瘤部位及形态学,辅之以免疫组织化学诊断.     

Pleomorphic carcinoma with osteoclastic giant cells of the breast: Immunohistochemical differentiation between coexisting neoplastic and reactive giant cells

Herein is described a unique case of breast carcinoma with two different types of giant cells noted in both cytological and histological specimens. A 51-year-old Japanese woman noticed a hard mass in the upper outer quadrant of her left breast. Aspiration cytology exhibited numerous anaplastic giant cells; the cytological diagnosis was high-grade ductal carcinoma, although a few osteoclastic giant cells were also observed. A left simple mastectomy and sentinel lymph node biopsy were performed. Histologically, approximately 90% of the tumor was composed of giant cells; conventional invasive ductal carcinoma and ductal carcinoma in situ were found focally at the periphery of the tumor. The main part of the tumor contained both anaplastic, neoplastic giant cells and non-neoplastic, osteoclastic giant cells that were distinguishable from nuclear atypism. The presence of the two types of giant cells was also confirmed on immunohistochemistry using a histiocytic marker (CD68) and two epithelial markers (AE1/AE3 and CAM5.2). Based on the latest World Health Organization classification, the diagnosis was pleomorphic carcinoma with osteoclastic giant cells. To the authors' knowledge there has been no previous report on this subject except for a single case mentioned in Rosen's Breast Pathology .     

Gastric small cell carcinoma with squamous and neuroendocrine differentiation.

A rare gastric carcinoma containing diverse components, that is, neuroendocrine (small cell carcinoma), squamous and gland-like elements in an 82 yr old woman is described. Radiologic examination revealed a large ulcerated tumor, and a Borrmann type II tumor, 6.5 x 5 cm, was found in the resected stomach. Histologically, the tumor was mainly composed of small cells with hyperchromatic nuclei and scant cytoplasm. Argyrophilic granules were seen in these cells. There were also scattered foci of large cells with features of squamous cells, and many intermediate cells with oncocytic cytoplasm. The small cancer cells were positive for chromogranin A and neuron specific enolase. Squamous cell nests were positive for high molecular cytokeratin (CK), and intermediate cells were positive for low molecular CK. Electron microscopic examination revealed secretory granules in the small cells and tonofilaments in the squamous cells. This tumor might have originated from the pluripotential stem cell in the gastric epithelium.     

Morphological heterogeneity of the simultaneous ipsilateral invasive tumor foci in breast carcinoma: A retrospective study of 418 cases of carcinomas

The aim of this paper was to assess whether the morphological appearance (i.e. histological tumor type and histological grade) of simultaneous invasive breast carcinoma foci is heterogeneous, since it is known that adjuvant therapy is established according to these parameters. Patients with simultaneous breast tumors in which only the features of the largest neoplastic focus are reported could thus be undertreated.     

Mammary carcinoma with osteoclast-like giant cells: a case report

Mammary carcinoma with osteoclast-like giant cells is rare, and comprises less that 2% of breast carcinoma cases. Herein, we present a case of a 45-year-old woman who underwent breast lumpectomy and sentinel lymph node biopsy for a solitary well defined breast tumor. Histological examination revealed an invasive tumor composed of ducts, small nests and cribriform formations intermixed with a prominent osteoclast like giant cell component. The background stroma is hemorrhagic with conspicuous hemosiderin deposition. The paper will outline the clinico-pathologic characteristic features of this uncommon subtype as well as the current understanding on the pathogenesis of the osteoclast-like giant cells. The invasive carcinoma and the osteoclast-like giant cells staining patterns using immunohistochemical stains for estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, receptor activator of nuclear-kB, RANK ligand, and matrix metalloproteinase 1 are reported.     

Mucinous cystadenocarcinoma of the breast with a basal-like immunophenotype

Mucinous cystadenocarcinoma (MCA) of the breast is extremely rare and was only recently described as a distinct variant of invasive ductal carcinoma of the breast. A case of MCA is reported in a 41-year-old woman. Mammographic and ultrasonographic examinations showed an irregularly shaped 10.0 × 8.0 × 5.5 cm lesion with patching calcification in the upper outer quadrant of the left breast. The gross examination revealed that the tumor has a well-circumscribed edge with a gelatinous cut surface and hemorrhage and necrosis were also noticed in the mass. Microscopically, the mass resembled mucinous cystic neoplasm of the ovary and pancreas closely, with cystic areas lined by columnar mucinous cells and associated with abundant extracellular and intracellular mucin, which is distinctively different from mucinous carcinoma with typically nests of low grade neoplastic cells floating in the mucin pool. The tumor cells were positive for CK7, CK20 and CDX2 were negative and displayed a typical immunophenotype of basal-like breast cancer (ER, PR, HER2 were negative, CK5/6 and EGFR were positive). Metastatic carcinoma was identified in three of 14 axillary lymph nodes. We describe here a very unusual case of breast MCA with basal-like immunophenotype.     

Invasive breast cancer: Current perspectives and emerging views

Invasive breast cancer constitutes a heterogeneous group of tumors. They comprise various histological types that differ in clinical presentation, imaging features, histopathological characteristics, biomarker profiles, prognostic and predictive parameters. The current classification of invasive breast cancer is based primarily on histopathological features. Invasive carcinoma of no special type accounts for the majority, with some rare entities also being described. With recent research and advances, there are emerging concepts, including new genetic insights of invasive breast cancer and the role of the stromal microenvironment. With greater understanding of the pathogenesis of invasive breast cancer, changes based on the correlation of histologic and genetic findings have been incorporated in the latest World Health Organization classification of breast tumors. Medullary carcinomas are subsumed as invasive carcinoma of no special type with basal‐like and medullary features, regarded as part of the spectrum of tumor infiltrating lymphocyte‐rich breast cancers. Tall cell carcinoma with reversed polarity is proposed as a distinct entity in recognition of unique IDH2 mutations. This article reviews conventional prognostic parameters, new histological entities, and updates on breast cancer classification, with inclusion of some genetic insights into breast cancer and the role of tumor infiltrating lymphocytes.     

Synchronous bilateral non-Hodgkin’s diffuse large B-cell lymphoma of the breast and left breast invasive ductal carcinoma: a case report and review of literature

Lymphoma of the breast is unusual, and synchronous bilateral lymphoma and carcinoma of the breast is extremely rare. We present the case of a 51-year-old woman who found a mass in her left breast. Ultrasound scan findings revealed nodules at the 2 o’clock position in her left breast and focal dilation of the duct at the 8-9 o’clock and 10 o’clock position in her right and left breasts, respectively. A left breast ultrasound-guided core needle biopsy and right breast segmental excisional biopsy were performed. Pathological and immunohistochemical examination revealed left breast invasive ductal carcinoma and right breast diffuse large B-cell lymphoma of the non-germinal center type. Pathological examination of the left breast modified radical mastectomy specimen revealed synchronous invasive ductal carcinoma (grade III) and diffuse large B-cell lymphoma. The patient received chemotherapy and bone marrow transplantation in another hospital. Based on a review of the relevant literature, we discuss the diagnosis, clinical features, treatment, and prognosis of synchronous breast lymphoma and invasive ductal carcinoma.     

Pleomorphic lobular carcinoma in a male breast: a case report with review of the literature

Invasive lobular carcinoma (ILC) is a distinct type of breast carcinoma and represents 5-15% of invasive breast carcinomas in female. However, the occurrence of ILC is exceptional in male breast, and the incidence is 1.5-1.9% of male breast carcinomas. Herein, we report a case of pleomorphic lobular carcinoma in a male breast. A 76-year-old Japanese male with a history of treatment with a progestational agent for prostate cancer presented with a right breast tumor. Magnetic resonance imaging showed gynecomastia of bilateral breasts and an irregular-shaped nodule in his right breast. Histopathological study revealed infiltrative neoplastic growth of discohesive tumor cells arranged in single-filed linear cords or trabeculae. These neoplastic cells had variable-sized large nuclei containing occasional nucleoli. Immunohistochemically, these tumor cells lacked E-cadherin expression. Accordingly, an ultimate diagnosis of pleomorphic lobular carcinoma was made. This is the third documented case of pleomorphic lobular carcinoma of male breast. Our analyses of the clinicopathological features of this type of tumor revealed that patients were middle-aged or elderly men, and all cases were free from lymph node metastases or recurrence. Gynecomastia and a history of hormonal agent intake were present only in the current case. The most commonly proposed risk factor for the development of male breast cancer is elevated level of estrogen, and a possible link between the development of male breast cancer and estrogen therapy for prostate cancer has been suggested. The clinicopathological features of ILC of male breast remains unclear; therefore, additional studies are needed to clarify them.     

Fine needle aspiration cytology of solid neuroendocrine carcinoma of the breast: a case report

We report a case of neuroendcrine (NE) carcinoma in the right breast of a 67-year-old female, ultrasonography revealed a lesion composed of irregular hypoechoic masses and mammography showed asymmetric breast tissue. Histopathologic examination of the surgical sample showed a solid to nested proliferation of plasmacytoid cells that showed immunocytochemical positivity for chromogranin A, synaptophysin, CD56, and estrogen receptor. Our case was diagnosed as solid NE carcinoma. Though the findings of fine needle aspiration cytology reflected the histological features, we were not able to cytopathologic grounds only to predict the NE nature of this tumor. We performed immunocytochemistry using Chromogranin A, Synaptophysin, and CD56 on our cytologic smear retrospectively with positive results for all of the markers. When the cytopathologic examination of a given breast neoplasm is suggestive of NE differentiation, immunocytochemical staining for NE markers is generally useful for a correct preoperative diagnosis. An acurate preoperative diagnosis of NE carcinoma on FNAC can be achieved based on its distinctive cytomorphologic and immunocytochemical features.     

Breast carcinoma with osteoclast-like giant cells: A cytological-pathological correlation with a literature review

Breast carcinoma with osteoclast-like giant cells (OGCs) is a rare disease characterized by the infiltration of OGCs in the tumor; however, cytological aspects of this tumor type remain elusive. We examined the cytological features in fine needle aspiration (FNA) biopsy smears obtained from 5 patients who were histologically diagnosed with breast carcinoma with OGCs. We compared FNA and clinicopathological findings with results from the published literature. Histological assessment of the resected samples showed that all tumors exhibited a histological grade 1 phenotype with a predominant cribriform architecture. Four patients were estrogen receptor positive, and 1 patient showed a triple negative phenotype. All patients survived without tumor recurrence. In the FNA smears, tumor cells were arranged in loosely cohesive clusters, characterized by varying degrees of OGCs infiltration and rare formation of solid tumor nests. Occasionally, 2- or 3-dimensional clusters of tumor cells were found, accompanied by OGCs at the peripheral regions. In all patients, tumor cells were small without severe nuclear atypia. None of the patients showed significant background necrosis. In summary, cytological features of breast carcinoma with OGCs are characterized by loose aggregates of low grade tumor cells, the presence of OGCs, and the absence of necrosis, all of which were consistent with features reported previously. This peculiar form of breast tumors should be included in the differential diagnosis, when physicians encounter FNA findings including low grade ductal carcinoma with the admixture of multinucleated giant cells or OGCs.     

Poorly differentiated ('insular') carcinoma of the thyroid

Three cases of unusual poorly differentiated ('insular') carcinoma of the thyroid gland are presented. These three thyroid carcinomas were large; the tumors from patients 1 and 3 were encapsulated, and that from patient 2 showed invasive growth. Microscopically the tumors were characterized by welldefined solid nests (insulae), which were composed of rather small and uniform tumor cells with round to oval nuclei. Formation of small and colloid-containing follicles was associated with these nests to varying degrees. The tumors of patients 1 and 3 were composed entirely of insular components, but that of patient 2 was associated with small areas of welldifferentiated follicular carcinoma. The metastatic tumors of patients 1 and 2 were essentially similar to the primary with small foci of follicular carcinoma.
Patient 1 is alive with local and mediastinal node recurrences, but patient 2 died of the disease with local recurrences and metastases to lungs, bones and skin. Patient 3 had no recurrences and died of unrelated disease 5 years after surgery. The present study indicates that insular carcinomas have characteristic histologic features and a less favorable prognosis, confirming the findings of previous studies.