Low-grade Intraductal Carcinoma Research Articles

174. Intraductal carcinoma of the parotid gland – a rare salivary malignancy accompanied by a pleomorphic adenoma: case report and review of the literature

Low-grade intraductal carcinoma (LGIC) is an extremely rare salivary ductal malignancy. We present a case of an LGIC and pleomorphic adenoma presenting within the same parotid gland, and the potential challenges this uncommon situation poses.

Low-grade intraductal carcinoma of accessory parotid gland: a case report.

Salivary low-grade intraductal carcinoma (LGIDC) is a rare tumor that mainly occurs in the parotid. Thus far, LGIDC originating from the accessory parotid gland has been rarely reported in domestic and foreign literature. This study reports a case of LGIDC of the accessory parotid gland and a brief summary of its clinical features, diagnostic points, and treatment by reviewing the literature, with the aim of providing a reference for clinical practice and further research.

Concomitant Low-Grade Mucoepidermoid and Intraductal Carcinomas the Parotid Gland: Case Presentation with a Brief Review

The patient was a Japanese female and a former thyroid cancer patient. A computed tomography scan indicated a small mass in the right parotid gland about 14 years after therapy for thyroid cancer. Pleomorphic adenoma was suspected by contrast-enhanced magnetic resonance imaging. Three years later, when she was 60 years old, fine needle aspiration cytology failed to determine a diagnosis and superficial parotidectomy was performed. There have been no signs of recurrence or metastasis for about 2 years thereafter. Histological examination revealed two histological types of low-grade mucoepidermoid carcinoma and low-grade intraductal carcinoma coexisting within the parotid mass. Although closely located, the two types of carcinoma had not intermingled. The mucoepidermoid carcinoma formed multilocular cystic structures, in which mucous, intermediate, and non-keratinizing squamous cells were intermingled. Exclusively predominant intraductal growth in the intraductal carcinoma showed a combination of cribriform and papillary-cystic patterns and diffuse positive reaction for S100 protein. Fluorescence in situ hybridization demonstrated the mucoepidermoid carcinoma had split signals for the MAML2 gene but no split signals were detected for the MAML2 and ETV6 genes in the intraductal carcinoma. We discuss the histomorphological features and diagnostic problems of the present case and the literature is briefly reviewed.

Concomitant Low-Grade Mucoepidermoid and Intraductal Carcinomas the Parotid Gland: Case Presentation with a Brief Review

The patient was a Japanese female and a former thyroid cancer patient. A computed tomography scan indicated a small mass in the right parotid gland about 14 years after therapy for thyroid cancer. Pleomorphic adenoma was suspected by contrast-enhanced magnetic resonance imaging. Three years later, when she was 60 years old, fine needle aspiration cytology failed to determine a diagnosis and superficial parotidectomy was performed. There have been no signs of recurrence or metastasis for about 2 years thereafter. Histological examination revealed two histological types of low-grade mucoepidermoid carcinoma and low-grade intraductal carcinoma coexisting within the parotid mass. Although closely located, the two types of carcinoma had not intermingled. The mucoepidermoid carcinoma formed multilocular cystic structures, in which mucous, intermediate, and non-keratinizing squamous cells were intermingled. Exclusively predominant intraductal growth in the intraductal carcinoma showed a combination of cribriform and papillary-cystic patterns and diffuse positive reaction for S100 protein. Fluorescence in situ hybridization demonstrated the mucoepidermoid carcinoma had split signals for the MAML2 gene but no split signals were detected for the MAML2 and ETV6 genes in the intraductal carcinoma. We discuss the histomorphological features and diagnostic problems of the present case and the literature is briefly reviewed.

Low-grade intraductal carcinoma of the parotid gland: Is it low-grade or locally aggressive?

<br>Low-grade salivary ductal carcinoma is a salivary gland tumor with clinically indolent behavior, characterized by intraductal growth. From 1996 to 2019, 54 case reports of Low-Grade Intraductal Carcinoma (LGIDC) were published in the literature. In the present article, we introduce a patient in our clinic who underwent surgery due to a diagnosis of LGIDC, about whom we make new clinical comments. A 75-year-old male patient presented to our clinic with a complaint of a mass in the right parotid area. After multiple biopsies, magnetic resonance imaging (MRI), and operations, the patient health is fine and patient's follow-up continues, now in the postoperative 1^st year, and there is no relapse sign on physical examination and MRI. After all, according to our clinical findings and observations, we thought that this tumor could possibly be considered a locally aggressive tumor that does not metastasize, similar to a basal cell carcinoma.<br>

Exosomes exist in nipple discharge of breast cancer.

Exosomes exist in nipple discharge of breast cancer.

Low Grade Intraductal Carcinoma of Palate: An Extremely Rare Entity with Review of Literature.

Low-grade intraductal carcinoma (LG-IDC) is the new World Health Organization designation for tumors previously called "low-grade cribriform cystadenocarcinoma" and "low-grade salivary duct carcinoma". LG-IDC is a rare low grade malignant salivary gland neoplasm. A 56-year old woman presented with a painless swelling on the right posterior part of palate of 2months duration. Radiographic examination revealed heterogenously enhancing soft tissue mass on right side of palate. A provisional diagnosis of pleomorphic adenoma was executed and local excision was done. The tumor had a typical feature of intraductal growth pattern composed of low grade ductal epithelial cells with cribriform and micropapillary patterns forming true "Roman bridges". Immunohistochemically myoepithelial cells displayed p63 around all tumor islands. The case was diagnosed as LG-IDC. LG-IDC is an extremely rare entity and awareness of this entity is important to avoid erroneous diagnosis and inappropriate treatment.

Intraductal Papillary Mucinous Neoplasms of Minor Salivary Glands With AKT1 p.Glu17Lys Mutation.

The spectrum of low-grade intraductal papillary proliferations of the salivary glands is heterogenous, and reproducible morphologic diagnostic criteria have not yet been established. Recognized types are sialadenoma papilliferum, inverted ductal papilloma, and intraductal papilloma, but some lesions have been possibly included in the morphologic spectrum of cystadenoma or low-grade intraductal carcinomas. We herein present detailed morphologic, immunophenotypic, and genotypic features of 3 minor salivary gland neoplasms affecting 2 men (aged 65 and 71 y) and 1 woman (aged 78 y). They ranged in size from 1 to 2.5 cm. All tumors showed atypical papillary intraductal growth that presented either as uninodular/unicystic lesions (intraductal papilloma-like; n=2) or as a discontinuous growth along the ductal system in a manner similar to pancreatic intraductal papillary mucinous neoplasm (n=1). Variable cytologic and architectural atypia was observed, ranging from bland intraductal papilloma-like features, to areas mimicking atypical ductal hyperplasia and low-grade ductal carcinoma in situ of the breast. Amplicon-based massive parallel sequencing revealed an identical AKT1 p.Glu17Lys mutation in all 3 cases, but absence of concurring mutations in other genes of the RAS or PI3K pathway. This small series represents the first genetic study on salivary intraductal papillary neoplasms. Our cases showed significant variation in the degree of cytologic and architectural atypia, which overlaps with intraductal papillomas at the one end and with low-grade intraductal carcinoma at the other end of the spectrum, suggesting a disease continuum. As the full biological and morphologic characteristics of these ductal papillary lesions remain to be defined, the noncommitted term "intraductal papillary neoplasms" might be more appropriate. Our novel genetic findings mirror similar activating mutations of AKT1 and other PI3K pathway members in intraductal papillary lesions of the breast and anogenital glands.

Low-grade intraductal carcinoma of the salivary gland with prominent oncocytic change: a newly described variant.

Low-grade intraductal carcinoma (LG-IDC) is a clinically indolent malignant tumour of the salivary glands. Because of its rarity, the histological variants of LG-IDC have not been well characterised. Herein, we describe five LG-IDC cases with prominent oncocytic change in the major salivary glands. We examined five cases, three males and two females (mean age=63years), of LG-IDC with oncocytic change. The sites affected by LG-IDC were the parotid and submandibular glands. The lesions were macroscopically unilocular or multilocular cysts with a solid tumour arising from the cyst wall. Smaller tumour cell nests were also observed. As with classic LG-IDC, the cyst wall was surrounded by myoepithelial cells with no invasive component. The tumour cells had abundant oncocytic cytoplasm and proliferated in a low-papillary, tubular or cribriform pattern. Immunohistochemically, the tumour cells were diffusely positive for pan-cytokeratin, S100, mammaglobin and antimitochondria antibody, and were negative for androgen receptor and gross cystic disease fluid protein-15. Unlike classic LG-IDC, some of these cases demonstrated focal invagination of myoepithelial cells in the intraductal tumour. Oncocytic LG-IDC should be recognised as a histologically unique variant of LG-IDC. Awareness of this entity is important to avoid erroneous diagnosis and inappropriate treatment for histological mimics.

43. Low grade cribriform cystadenocarcinoma: the cytology and histology of a rare salivary gland tumour

Low grade cribriform cystadenocarcinoma (LGCCC) is a rare low grade malignant neoplasm which occurs almost exclusively in the parotid gland. The lesion is also known as low grade intraductal carcinoma of the salivary gland, coined by Delgado et al. in 1996, due to its resemblance to atypical ductal hyperplasia or low grade ductal carcinoma in situ of the breast. The majority of patients are elderly and have a female predominance of 2:1. While there have been several case series and case reports in the literature about its histological and immunohistochemical features, only two studies in the English language literature have given any cytolomorpho-logical description. We present a case of a 62-year-old female with a right parotid mass. A fine needle aspiration showed a hypercelllular smear, with sheet-like and branching architecture, composed of fairly uniform cells with atypical features, in a mucoid/myxoid background. A diagnosis suggestive of a pleomorphic adenoma was given. Five months later, an excision of a 1.5 cm, solid-cystic mass was performed. Histological examination showed an intraductal proliferation of tumour cells akin to a breast low grade ductal carcinoma in situ with papillary and cribriform pattern. A focal area of microinvasion was present. Immunohistochemically, the luminal cells showed strong and diffuse positive cytokeratin and S-100 staining. The myoepithelial marker, calponin, highlighted the basal cells. Hence, a diagnosis of low grade cribriform cystadenocarcinoma was favoured. The characteristic features of this lesion are discussed, with focus given to the cytological findings and the diagnostic difficulties in fine needle aspirates, particularly due to lack in the current literature of definitive diagnostic criteria.

Low-Grade Salivary Duct Carcinoma or Low-Grade Intraductal Carcinoma? Review of the Literature

Low-grade salivary duct carcinoma (LG-SDC) is a rare neoplasm characterized by predominant intraductal growth, luminal ductal phenotype, bland microscopic features, and favorable clinical behavior with an appearance reminiscent of florid to atypical ductal hyperplasia to low grade intraductal breast carcinoma. LG-SDC is composed of multiple cysts, cribriform architecture with "Roman Bridges", "pseudocribriform" proliferations with floppy fenestrations or irregular slits, micropapillae with epithelial tufts, fibrovascular cores, and solid areas. Most of the tumor cells are small to medium sized with pale eosinophilic cytoplasm, and round to oval nuclei, which may contain finely dispersed or dark condensed chromatin. Foci of intermediate to high grade atypia, and invasive carcinoma or micro-invasion have been reported in up to 23 % of cases. The neoplastic cells have a ductal phenotype with coexpression of keratins and S100 protein and are surrounded by a layer of myoepithelial cells in non-invasive cases. The main differential diagnosis of LG-SDC includes cystadenoma, cystadenocarcinoma, sclerosing polycystic adenosis, salivary duct carcinoma in situ/high-grade intraductal carcinoma, and papillary-cystic variant of acinic cell carcinoma. There is no published data supporting the continuous classification of LG-SDC as a variant of cystadenocarcinoma. Given that most LG-SDC are non-invasive neoplasms; the terms "cribriform cystadenocarcinoma" and LG-SDC should be replaced by "low-grade intraductal carcinoma" (LG-IDC) of salivary gland or "low-grade intraductal carcinoma with areas of invasive carcinoma" in those cases with evidence of invasive carcinoma.

Intraductal Carcinoma of Salivary Gland (So-Called Low-Grade Cribriform Cystadenocarcinoma) Arising in an Intraparotid Lymph Node

Since the first description of an entirely intraductal epithelial proliferation of salivary gland by Chen in 1983 as an "intraductal carcinoma", there have been several dozen reported cases with the same and various additional names including "low-grade salivary duct carcinoma", "low-grade cribriform cystadenocarcinoma" and "carcinoma in situ" of salivary gland. These refer to a combination of nests and cysts of varying size formed by a cellular proliferation resembling atypical ductal hyperplasia or ductal carcinoma in situ of the breast. The lesions are generally entirely intraductal with low, intermediate or high-grade dysplasia. Occasional benign tumors of salivary gland, particularly Warthin tumor and rare salivary carcinomas may arise within an intraparotid lymph node. In addition, intraparotid lymph nodes are a routine location for metastatic disease. A case of a 59-year-old female with a parotid mass is described, which grossly had the appearance of a Warthin tumor. Microscopically, it was an entirely intranodal proliferation of cells with diffuse AE1/AE3 and S100 positivity. The nests and cysts were completely surrounded by a rim of non-neoplastic myoepithelial cells, which were positive for CK14, p63, SMA, MSA and calponin. The tumor cells were negative for these markers. The cells were only focally positive for AR and BRST-2. They showed negligible MIB-1 staining. This report describes, for the first time, an entirely intranodal location for a low-grade intraductal carcinoma (so-called low-grade cribriform cystadenocarcinoma).

Cytological study of 20 cases of solid‐papillary carcinoma of the breast

Solid-papillary carcinoma (SPC) of the breast is a rare variant of low-grade intraductal carcinoma but there are few cytological studies. We examined 20 cases of SPC of the breast, aged 31-80 (mean age 66.0 yr), to define the cytological features. In each of the cytological specimens, we could find both malignant and benign cytological features; the former were characterized by hypercellularity, highly discohesive clusters, numerous isolated cells, and severe overcrowding cells, while the latter were marked by small and bland nuclei, a low nuclear-cytoplasmic ratio, and inconspicuous nucleoli. Neither abnormal naked nuclei of tumor cell origin nor oval naked nuclei of myoepithelial cell origin were seen. We also reviewed the cytological findings of SPC as well as neuroendocrine carcinomas with intraductal components that had been reported and we concluded that the coexistence of malignant and benign features was the most characteristic cytological feature of SPC.

Proliferating activity in columnar cell lesions of the breast

With the introduction of mammographic screening, columnar cell lesions (CCLs) are observed more and more frequently because they are often associated with microcalcifications. Until now, the proliferative activity of these lesions has not been previously evaluated. Ki67 index was performed by immunohistochemistry in CCLs without atypia [columnar cell change (CCC) n = 20 and columnar cell hyperplasia without atypia (CCH without atypia) n = 20], flat epithelial atypia (FEA DIN1A n = 20), low-grade intraductal carcinoma (DIN1C n = 20), high-grade intraductal carcinoma (DIN 2-3 n = 20). Adjacent terminal duct-lobular unit (TDLU) of normal breast tissue served as control. Ki-67 index is extremely low and close in CCLs without atypia (CCC mean 0.1% and CCH mean 0.76%) and paradoxically is lower than in normal TDLU (mean 2.4%) (p < 0.001). In the FEA, in comparison with normal TDLU and CCLs without atypia, the Ki67 is higher (mean 8.2%) (p < 0.001) but extremely close to those of DIN1C (mean 8.9%) (p = 0.6 NS). Lastly, the Ki67 index is higher in DIN 2-3 (mean 25.4%) than in CCLs without atypia and FEA (p < 0.001). CCLs are disparate lesions having in common cells with columnar configuration but different proliferative characteristics. These data represent findings of biological interest which could help us to better understand these controversial lesions.

Clinicopathologic implications of E-cadherin reactivity in patients with lobular carcinoma in situ of the breast

The current study addressed two questions pertaining to lobular carcinoma in situ (LCIS) of the breast. First, does the risk of a subsequent carcinoma decrease over time after an LCIS biopsy and second, what is the clinical significance of E-cadherin-reactive LCIS? Eighty-two consecutive patients with a biopsy containing LCIS only, no prior history of breast carcinoma, and follow-up information available for the period 1955-1976 were reviewed. No patients underwent a mastectomy for LCIS. Four hundred eighty-six sections were stained with E-cadherin. E-cadherin reactivity was correlated with clinicopathologic features of the LCIS and subsequent tumors. The mean number of blocks stained per case was 5.9. The mean follow-up period was 21.6 years. Sixteen patients (19.5%) developed 21 subsequent invasive carcinomas (9 ipsilateral, 2 contralateral, and 5 bilateral carcinomas). The 10-year and 20-year actuarial rates of developing subsequent carcinoma were 7.8% and 15.4%, respectively. Six of the 21 carcinomas (29%) developed after 20 years. Nine LCIS cases (10.9%) had focal E-cadherin reactivity. When compared with patients with nonreactive LCIS, patients with E-cadherin-reactive LCIS more frequently developed a subsequent ipsilateral carcinoma that had a ductal component (55.5% vs. 12.3%; P < 0.01). The subsequent carcinomas also developed after significantly shorter time periods (mean of 7.6 years vs. 19.6 years; P < 0.01). LCIS appears to confer a persistent, increased risk of subsequent breast carcinoma that does not appear to decrease over time. E-cadherin reactivity appears to identify a subset of LCIS patients with risk factors for subsequent carcinoma similar to those of patients with low-grade intraductal carcinoma.