p63 Immunohistochemistry in the distinction of adenoid cystic carcinoma from basaloid squamous cell carcinoma.

Morphologic distinction of high-grade adenoid cystic carcinoma from basaloid squamous cell carcinoma can be difficult. Equivocal diagnoses can mislead treatment. We have investigated the possibility that immunohistochemical staining for the presence of p63, a novel epithelial stem-cell regulatory protein, could be a useful means of distinguishing these two neoplasms. Archival, routinely processed slides were subjected to citrate-based antigen retrieval, exposure to anti-p63 monoclonal 4A4, and developed with a streptavidin-biotin kit and diaminobenzidine as chromogen. p63 was detected in 100% of the adenoid cystic carcinomas (n=14) and 100% of basaloid squamous cell carcinomas (n=16). Basaloid squamous cell carcinomas consistently displayed diffuse p63 positivity, with staining of nearly 100% of tumor cells. In contrast, adenoid cystic carcinoma displayed a consistently compartmentalized pattern within tumor nests. Compartmentalization was manifested in two patterns: (1) selective staining of a single peripheral layer of p63-positive cells surrounding centrally located tumor cells that were p63-negative and (2) tumor nests consisting of multiple contiguous glandular/cribriform-like units of p63-positive cells surrounding or interspersed with p63-negative cells. p63 immunostaining constitutes a specific and accurate means of distinguishing adenoid cystic carcinoma from basaloid squamous cell carcinoma. p63 positivity in adenoid cystic carcinoma appears to be homologous to that seen in the basal and/or myoepithelial compartments of salivary gland and other epithelia, and may signify a stem-cell-like role for these peripheral cells. Diffuse p63 positivity in basaloid squamous cell carcinoma suggests dysregulation of p63-positive stem cells in poorly differentiated squamous carcinoma.     

p63免疫组化染色在腺样囊性癌和基底样鳞状细胞癌鉴别诊断中的价值

腺样囊性癌与基底样鳞状细胞癌的鉴别有时非常困难，而诊断不明确则容易导致二者的治疗错误。p63作为一个新的上皮干细胞调控蛋白，可在人类多种正常组织如鳞状上皮、尿路上皮、乳腺和涎腺的肌上皮细胞等表达，也可表达于涎腺多形性腺瘤和癌中。为了探讨p63免疫组化染色在腺样囊性癌和基底样鳞状细胞癌鉴别诊断中的价值，     

Immunoreactivity for c-kit and p63 as an adjunct in the diagnosis of adenoid cystic carcinoma of the breast.

Adenoid cystic carcinoma of the breast represents a unique clinicopathologic entity with a variable histological appearance and a relatively indolent clinical course in most of the cases. Adenoid cystic carcinoma may be difficult to differentiate from infiltrating duct carcinomas, and in particular from tubular and cribriform carcinomas, especially in core or vacuum-assisted biopsies. We evaluated the prevalence of c-kit, p63, and e-cadherin immunoreactivity in a series of 20 adenoid cystic carcinomas, comparing the results with those obtained in a series of infiltrating tubular carcinomas and infiltrating cribriform carcinomas. The hormone receptor status, proliferation labeling index, and HER/2 immunoreactivity had been previously investigated in all the cases. Three (15%) adenoid cystic carcinomas and all infiltrating tubular and cribriform carcinomas showed estrogen receptor and/or progesterone receptor immunoreactivity (P < 0.00001 for estrogen and P = 0.00002 for progesterone receptors). Adenoid cystic carcinomas consistently lacked any immunoreactivity for HER/2, whereas three (15%) infiltrating and cribriform carcinomas showed weak and incomplete membrane staining (P = 0.23077). Membranous immunoreactivity for c-kit was found in all except one (predominantly basaloid) adenoid cystic carcinomas (95%), and in none of the infiltrating tubular and cribriform carcinomas (P < 0.00001). Nuclear immunoreactivity for p63 was found in all except three (predominantly basaloid) adenoid cystic carcinomas (85%) and in none of the infiltrating tubular and cribriform carcinomas (P < 0.00001). All infiltrating tubular and cribriform carcinomas and 18/20 (90%) adenoid cystic carcinomas showed immunoreactivity for e-cadherin (P = 0.48718). In summary, adenoid cystic carcinomas showed the following phenotype: estrogen receptor-/progesterone receptor-/c-kit+/p63+ (13 cases, 65%), estrogen receptor-/progesterone receptor/c-kit+/p63- (three cases, 15%), estrogen receptor-/progesterone receptor-/c-kit-/p63+ (one case, 5%), estrogen receptor+/progesterone receptor+/c-kit+/p63+ (two cases, 10%), and estrogen receptor+/progesterone receptor-/c-kit+/p63+ (one case). By contrast, all the infiltrating tubular and cribriform carcinomas showed the estrogen receptor+/progesterone receptor+/c-kit-/p63- phenotype. Our data provide evidence that immunoreactivity for c-kit and/or p63 may be useful in differentiating adenoid cystic carcinomas from other types of breast cancer.     

Trisomy 13 as a primary chromosome aberration in acute leukemia.

Four patients with acute leukemia displayed trisomy 13 as the primary chromosome abnormality. The two patients with acute nonlymphocytic leukemia FAB-type M1 (ANLL-M1) had the karyotypes 47,XY,+13/48,XY,+13,+13 and 47,XX,+13, a patient with the hypogranular form of ANLL M3 had 47,XX,+13, and the fourth patient, who had acute undifferentiated leukemia (AUL), had the karyotype 47,XY,+13/48,XY,+8,+13. Including these four cases, a total of 24 hematologic neoplasms with an extra chromosome 13 as the sole aberration have now been reported. Except for the AUL, all have been of myeloid origin--20 ANLL, one myelodysplastic syndrome, and two chronic myeloproliferative disorders. Trisomy 13 as the sole acquired karyotypic abnormality therefore seems to be strongly associated with myeloid differentiation of the neoplastic cells and with a differentiation block leading to acute leukemia.     

Laminin and fibronectin in adenoid cystic carcinoma.

The distribution of fibronectin and laminin was examined by immunohistochemistry in 11 adenoid cystic breast carcinomas, six adenoid cystic carcinomas of mouth and salivary gland, and six cribriform ductal breast carcinomas. Both proteins were present lining cystic lumina and around tumour islands in all the adenoid cystic breast carcinomas and in five of six salivary gland tumours. Abundant laminin and fibronectin were dispersed among adenoid cystic tumour cells arranged in sheets. One adenoid cystic carcinoma from buccal mucosa showed a transition from a cribriform tumour positive for both fibronectin and laminin to a cribriform tumour negative for fibronectin and laminin to undifferentiated carcinoma. Fibronectin and laminin seemed to disappear simultaneously from tumour cell surfaces. Another adenoid cystic carcinoma from buccal mucosa was negative for fibronectin and laminin from the time of initial biopsy. This was the only tumour that gave rise to disseminated metastases, resulting in the death of the patient within two years of surgery. In cribriform invasive ductal breast carcinomas the linings of cystic lumina were always negative for fibronectin and laminin. Varying quantities were present at the tumour boundaries. We suggest that staining for fibronectin and laminin may be a valuable aid to the diagnosis of adenoid cystic carcinomas and that the absence of these proteins may have important prognostic implications.     

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.     

Primary adenoid cystic carcinoma of the esophagus

Immunohistochemical and electron microscopic findings of a primary adenoid cystic carcinoma of the esophagus from a 71-year-old male patient are described. An oval tumor in the middle intrathoracic esophagus was resected. The tumor appeared similar to a submucosal tumor and was histologically diagnosed as primary adenoid cystic carcinoma (ACC) of the esophagus. The patient has survived for 10 years postoperatively with no evidence of recurrence. Histologically, the tumor showed a cribriform, tubular or solid pattern. A small focus of squamous cell carcinoma (SCC) was found independently. Immunohistochemical results for keratin groups, S-100 protein and smooth muscle actin (αSMA) revealed similar profiles in the ACC tumor tissues and small ducts of the normal esphageal glands. By electron microscopy, tumor cells were found markedly similar to the small duct cells of the normal esophageal gland. These findings. indicate that ACC may originate from the esophageal glands, especially from cells of the small duct including intercalated duct.     

Observations by chromosome banding, FISH and immunohistochemistry in an adenoid cystic carcinoma with del(17)(p13) as the sole deviation

We report on an adenoid cystic carcinoma (ACC) with a clonal deletion of 17p as the only karyotypic abnormality. Using different chromosome 17-derived probes we showed by FISH that the deletion encompassed thep53 tumour suppressor gene. Immunohistochemical analysis revealed overexpression ofp53 protein in a subpopulation of cells, suggesting a mutation in the remainingp53 allele in these cells. Our findings provide novel information about possible progressional pathways in ACC, and demonstrate the value of combining conventional cytogenetic analysis with molecular cytogenetic and immunohistochemical methods. This approach is particularly useful in cases with minor cytogenetic abnormalities at the border of visibility.     

Distribution of mucosubstances in adenoid cystic carcinoma

Summary Two unusual carcinomas of the breast are described, containing nests of infiltrating neoplasm situated within stromal lacunar spaces, and surrounded by numerous benign appearing multinucleated giant cells. Within the stroma, there was extensive hemorrhage, hemosiderin pigment deposition, and large numbers of mononucleated inflammatory cells. The morphology of both tumors resembled the giant cell tumor of bone. Although a similar giant cell reaction has recently been described in association with a uterine leiomyosarcoma, we are aware of only two other examples of this entity in the breast, both reported over 40 years ago in the French literature. This is the first report in which electron microscopy confirmed the benign histiocytic nature of the giant cells. These cells had many of the ultrastructural features of multinucleated giant cells described in tissue culture, skeletal osteoclastomas, and foreign body granulomas. We propose that the giant cells arise from fusion of mononucleated stromal cells, and most likely are reactive histiocytic elements which are in some way related to the tumor cell nests. Further studies of these unusual neoplasms are needed to determine if the giant cell reaction in any way affects the prognosis of the patient.     

Expression of autophagy and ER stress-related proteins in primary salivary adenoid cystic carcinoma

Autophagy is the endogenous cellular pathway that facilitates cellular survival by maintaining energy homeostasis and macromolecular synthesis during cellular stress and nutrient deprivation. Endoplasmic reticulum (ER) stress is the process in which disruption of these physiological functions leads to an accumulation of unfolded proteins and induces the unfolded protein response (UPR). ER stress and autophagy are involved in human cancer. We investigated the expression of autophagic proteins (LC3 and beclin 1) and ER stress-related protein (GRP78) in head and neck adenoid cystic carcinoma tissue. Tissue samples from 79 cases of head and neck adenoid cystic carcinoma tissue were utilized for immunohistochemistry. LC3 expression was significantly correlated with lymph node involvement (P = .016) and TNM (P = .021). Beclin 1 expression was significantly correlated with the histological growth pattern (P = .002), the histological grade (P = .000), and longer survival (P = .000). GRP78 expression was significantly correlated with the histological growth pattern (P = .019), the histological grade (P = .019), and longer survival (P = .001). LC3 expression was positively correlated with beclin 1 expression (P = .000); LC3 and beclin 1 expressions were positively correlated with GRP78 expression respectively (P = .035) (P = .008). Our study describes the expression of LC3, beclin 1, and GRP78 in adenoid cystic carcinoma and its relationship with clinicopathologic factors and overall survival. These results suggest that LC3, beclin 1, and GRP78 may play an important role in the tumorigenesis of adenoid cystic carcinoma, and that beclin 1 and GRP78 may serve as new prognostic indicators for the outcome of patients with adenoid cystic carcinoma.     

Characterisation of adenoid cystic carcinoma of the breast by immunohistology.

An adenoid cystic carcinoma of the breast in a 78 year old woman was analysed immunohistologically for the production of type IV collagen, the expression of vimentin, epithelial membrane antigen (EMA) and steroid receptors, and the proliferative activity of the tumour cells. The data were compared with those obtained in eight adenoid cystic carcinomas of salivary glands and in ductal carcinomas of the breast with a cribriform growth pattern. The patients' ages were as follows: 45-80 years (mean 63.2) for the salivary gland carcinomas; 37-69 years (mean 50.6) for the ductal breast carcinomas. In contrast to the cribriform spaces of ductal carcinomas, the pseudocysts in adenoid cystic carcinomas were lined by type IV collagen. The opposite pattern was observed for EMA. Like the myoepithelium of normal breast, the myoepithelium-like cells of adenoid cystic carcinoma stained positive for vimentin while the ductular epithelium-like ones did not. All adenoid cystic carcinomas, including that of the breast, were negative for the oestrogen and progesterone receptors, unlike the ductal carcinomas. Proliferative activity of the adenoid cystic carcinoma of the breast was relatively low. These data broaden the range of antibodies suitable for differential diagnosis of both tumour types. They may explain the differences in prognosis, and they explain why hormonal treatment or radiotherapy of adenoid cystic carcinoma of the breast are often ineffectual.     

The selective expression of CD43 in adenoid cystic carcinoma.

CD43, a sialoglycoprotein expressed on hematopoietic cells, has only rarely been reported in nonhematopoietic tumors, mostly of colon. We describe CD43 expression by immunohistochemistry and mRNA in situ hybridization in adenoid cystic carcinomas (ACCs). CD43 immunoreactivity with 2 different antibodies was detected mainly in ACC but also 1 membranous type basal cell adenocarcinoma and 1 colonic adenocarcinoma. Nine of 20 (45%) ACC (8/17 salivary/mucoserous and 1/3 mammary) showed immunoreactivity with clone MT1 whereas 4 (23.5%) salivary ACC also showed immunoreactivity with clone DF-T1. The few high-grade, angioinvasive ACC in our study did not seem to express CD43. CD43 mRNA was detected by in situ hybridization in 2 of the 3 ACC that were CD43 positive on immunohistochemistry but not on any CD43 negative cases tested. Hence, CD43 seems to be selectively expressed in a subset of ACC and its significance in salivary tumors is discussed.     

Cytologic diagnosis of adenoid cystic carcinoma of salivary glands.

The cytomorphologic features in fine-needle aspiration (FNA) biopsies from 31 primary and 33 recurrent adenoid cystic carcinomas (ACC) were investigated. The correct FNA diagnosis was established in 24 of 31 primary ACC (77%). The diagnostic clue in aspirates from ACC are large globules of extracellular matrix, partially surrounded by basaloid tumor cells. In FNAs with predominance of basaloid tumor cells, but lacking characteristic globules, all other benign and malignant salivary gland tumors of epithelial-myoepithelial differentiation should be considered in the cytologic diagnosis. Pleomorphic adenoma is most frequently confused with ACC, and therefore, the cytologic findings in FNAs from 50 pleomorphic adenomas were compared with those diagnosed as ACC. Furthermore, rare neoplasms of salivary glands with epithelial-myoepithelial cell differentiation, including basal-cell adenoma and carcinoma, epithelial-myoepithelial carcinoma, and polymorphous low-grade adenocarcinoma, as well as some nonsalivary gland neoplasms presenting an adenoid cystic pattern, must be considered. The cytologic features of these entities are discussed in detail with respect to the cytologic diagnostic criteria of ACC.     

Mutations in components of the Wnt signaling pathway in adenoid cystic carcinoma.

The Wnt signaling pathway is essential for normal development and organogenesis. However, inappropriate activation of Wnt signaling, which results in the nuclear translocation of beta-catenin, is associated with the development of various types of neoplasm. In this study, we investigated possible mutations in the genes for components of this pathway, namely, CTNNB1 (the gene for beta-catenin), AXIN1, and APC, in adenoid cystic carcinoma, by PCR, analysis of single-strand conformational polymorphism, and sequencing. Among a total of 20 cases of adenoid cystic carcinoma, seven cases (35%) were associated with mutations in one or more of these three components. A mutation in CTNNB1 was detected in one case. Five cases, including the case with a mutation in CTNNB1, were associated with missense mutations in AXIN1. An aberration in the mutation cluster region of APC was detected in two cases. Mutations trended to be detected more frequently in adenoid cystic carcinoma with solid growth pattern than that with tubular and cribriform growth pattern. In the cases in which we detected mutations, it is possible that the presence of the abnormal products of the mutated genes resulted in the inappropriate activation of the Wnt signaling pathway to tumorigenesis and the growth of adenoid cystic carcinoma.     

Cytological diagnosis of adenoid cystic carcinoma breast--a case report.

The cytologic features of a case of adenoid cystic carcinoma of breast diagnosed on fine needle aspiration cytology (FNAC) in a 52 years old female are described. FNAC was carried out on outer quadrant of breast. The characteristic cytological features were numerous single to branching small round to Avoid cells at places forming microacini. Numerous pink hyaline globules of variable sizes were seen along with finger like projections containing basement membrane material.