Cribriform Component Research Articles

Intratumoral and peritumoral radiomics model for the preoperative prediction of cribriform component in invasive lung adenocarcinoma: a multicenter study.

This study aimed to investigate the predictive value of intratumoral and peritumoral radiomics model for the cribriform component (CC) of invasive lung adenocarcinoma (LUAD). The 144 patients with invasive LUAD from our center were randomly divided into training set (n = 100) and internal validation set (n = 44) in a ratio of 7:3, and 75 patients from center 2 were regarded as the external validation set. Clinical risk factors were examined using univariate and multivariate logistic regression to construct the clinical model. We extracted radiomics features from gross tumor volume (GTV), gross and peritumoral volume (GPTV), and peritumoral volume (PTV), respectively. Radiomics models were constructed with selected features. A combined model based on the optimal Radscore and clinically independent predictors was constructed, and its predictive performance was assessed by receiver operating characteristic curve (ROC), calibration curve, and decision curve analysis (DCA). The area under curves (AUCs) of the GTV model were 0.882 (95% CI 0.817-0.948), 0.794 (95% CI 0.656-0.932), and 0.766 (95% CI 0.657-0.875) in the training, internal validation, and external validation sets, and the PTV model had AUCs of 0.812 (95% CI 0.725-0.899), 0.749 (95% CI 0.597-0.902), and 0.670 (95% CI 0.543-0.798) in the training, internal validation, and external validation sets, respectively. However, the GPTV radiomics model showed better predictive performance compared with the GTV and PTV radiomics models, with the AUCs of 0.950 (95% CI 0.911-0.989), 0.844 (95% CI 0.728-0.959), and 0.815 (95% CI 0.713-0.917) in the training, internal validation and external validation sets, respectively. In the clinical model, tumor shape, lobulation sign and maximal diameter were the independent predictors of CC in invasive LUAD. The combined model including independent clinical predictors and GPTV-Radscore show the considerable instructive to clinical practice, with the AUCs of 0.954(95% CI 0.918-0.990), 0.861(95% CI 0.752-0.970), and 0.794(95% CI 0.690-0.898) in training, internal validation, and external validation sets, respectively. DCA showed that the combined model had good clinical value and correction effect. Radiomics model is a very powerful tool for predicting CC growth pattern in invasive LUAD and can help clinicians make the strategies of treatment and surveillance in patients with invasive LUAD.

Sensitivity of multiparametric MRI and targeted biopsy for detection of adverse pathologies (Cribriform gleason pattern 4 and intraductal carcinoma): Correlation of detected and missed prostate cancer foci with whole mount histopathology.

Accurate preoperative detection of prostate cancer (PCa) exhibiting "cribriform" morphology (intraductal carcinoma [IDC-P] or cribriform Gleason pattern 4 [CrP4]) is important as it is independently associated with a variety of adverse clinical outcomes. The sensitivity of multiparametric magnetic resonance imaging (mpMRI) in the detection of PCa exhibiting "cribriform" morphology remains controversial. A total of 117 eligible men with prospectively reported mpMRI who underwent in-bore MRI targeted biopsy followed by whole-mount radical prostatectomy (RP) were analyzed for lesion-level imaging-pathology correlation. Of the 206 PCa foci at RP (117 index and 89 non-index), 74% (152/206) were detected by mpMRI. Of the 54 tumors missed by mpMRI, most were non-index (98%, 53/54), grade group (GG) 1 (68%, 37/54) or GG 2 (26%, 14/54), with a median size of 1.0 cm (range, 0.7-1.5 cm), and non-cribriform morphology (96%, 52/54). Cribriform morphology was detected in 26% (53/206) of all tumors, and although targeted biopsies identified 96% (51/53) of these cancers, the cribriform component was depicted in only 45% (24/53). Of these, mpMRI detected all (100%, 44/44) index and 78% (7/9) of the non-index tumors. At univariable analysis, tumor size greater than 5 mm, % pattern 4 > 5%, cribriform morphology, zone (transition versus peripheral zone), and region (apex versus mid/base) were significantly associated with tumor visibility at mpMRI. At multivariable analysis, only tumor size, presence of any pattern 4, and peripheral zone remained significant predictors for visibility by mpMRI. At a lesion level, mpMRI offers high sensitivity for the detection of cribriform morphologies, however, the cribriform component is frequently missed by targeted biopsies. The MRI visibility is significantly associated with larger tumor size, presence of Gleason pattern 4, and peripheral zone location.

Looking for a Simplified Diagnostic Model to Identify Potentially Lethal Cases of Prostate Cancer at Initial Diagnosis: An ImGO Pilot Study.

Simple SummarySeveral genetic anomalies are recurrent in prostate cancer (PC) and allow this disease to be classified into distinct molecular subtypes; however, these anomalies have no predictive role and have limited relevance for clinical practice. Within this pilot study, metastatic castration-resistant PC (mCRPC) and metastatic castration-sensitive PC (mCSPC) were used for identifying and understanding lethal prostate tumor clones, from a genomic point of view. Some elements, such as a high Gleason Score and the presence of a cribriform pattern or intraductal carcinoma were evaluated as phenotypic markers of potentially lethal PC. Our results provide hypothesis-generating data, as the idea of evaluating mCSPC and mCRPC as a phenotypic/biologic model able to be translated in clinical practice. The confirmation of a high incidence of TP53 and BRCA2 mutations in larger trials may find a therapeutic implication through the choice of whether or not to use “more” therapy in respect to “selective” treatments approaches.The recurrent genetic anomalies used to classify prostate cancer (PC) into distinct molecular subtypes have limited relevance for clinical practice. In consideration of WHO 2016 histological classification, which includes the introduction of Gleason Score 4 for patients with cribriform component and the definition of intraductal carcinoma as a new entity, a retrospective pilot study was conducted to investigate, by histological review, if there were any variations of Gleason Score and the incidence of intraductal carcinoma and cribriform pattern, intended as “phenotypic” markers of potentially lethal PC, among metastatic castration-sensitive PC (mCSPC) and metastatic castration-resistant PC (mCRPC) samples. Potentially predictive factors were also assessed. Among 125 cases, a variation in the Gleason Score was reported in 26% of cases. A cribriform (36%) or intraductal (2%) pattern was reported in a higher percentage. Of them, a primary Gleason pattern 4 was reported in 80% of cases. All patients with intraductal carcinoma present a BRCA2 mutation, also found in 80% of cases with a cribriform pattern. This pilot study documented some hypothesis-generating data, as the evaluation of de novo mCSPC and mCRPC as phenotypic/biologic model to be translated in clinical practice. A cribriform pattern/intraductal carcinoma might be a marker of potentially lethal PC. The high incidence of TP53 and BRCA2 mutations in de novo mCSPC may also have a therapeutic implication.

Prognostic significance of <i>PTEN</i>, <i>RB1</i> and <i>BRCA2</i> gene loss in patients with localized and locally advanced prostate cancer

Background. Prostate cancer is the most common malignant condition among oncological diseases of the genitourinary tract, which occupies the second place in male mortality from malignant neoplasms. At the same time, population of patients with prostate cancer is heterogeneous: in some patients, the disease does not require active treatment, while in others it progresses rapidly with the formation of metastatic castration-resistant prostate cancer. Therefore, the search for new predictive markers remains relevant.Objective. Analysis of the prognostic significance of the loss of heterozygosity of PTEN, RB1, TP53, BRCA1 and BRCA2 genes in patients with localized and locally advanced prostate cancer.Materials and methods. The study included 52 patients with prostate cancer, 31 (59.6 %) of whom had a localized form (T1-2N0M0), and 21 (40.4 %) - locally advanced (T3a-bN0/1M0). All patients underwent radical prostatectomy, followed by genotyping of postoperative and biopsy specimens to determine genetic alterations in the studied genes. Detection of deletions in the studied genes was carried out using the method of multiplex ligation-dependent probe amplification.Results. In 13 (25.0 %) patients in the postoperative specimen was detected deletion of PTEN gene, in 6 (11.5 %) - deletion of RB1 gene, and in 1 (1.9 %) - deletion of BRCA2 gene. At the same time, patients with loss of PTEN heterozygosity were more likely to have perineural invasion (p = 0.01) and lymph node involvement (p = 0.0003). Deletion of RB1 gene is associated with more frequent detection of high-grade tumors (p = 0.013), cribriform growth component (p = 0.002), and invasion of the periprostatic tissue (p = 0.005).Conclusion. Detection of loss of heterozygosity of PTEN and RB1 genes is a promising tool for clarifying the prognosis of the disease, which in the future will allow more accurately stratify patients into risk groups for biochemical relapse.

The visibility of prostate cancer concerning underlying histopathological variances: A single-center multiparametric magnetic resonance imaging study

PurposeTo investigate whether prostate cancer (PCa) lesions regarding histopathological composition exhibit different morphological features on multiparametric prostate MRI (mpMRI). MethodsWe investigated men with PCa with available mpMRI and whole-mount specimens between June 2015 to December 2020.The acquisition protocol consistent with the Prostate Imaging Reporting and Data System (PI-RADS). Two observers evaluated the images following the PI-RADS v2.1. guideline before biopsy and radical prostatectomy. The discrepancies were resolved in a joint meeting. A genitourinary pathologist reviewed the whole-digitalized mount specimens, and the lesions with Gleason score of 7 and above (3 + 4 and above), and/or cancers with a maximum diameter of 6 mm and more, and/or extraprostatic extension were accepted as clinically significant PCa. The PI-RADS scores and the diameter of the clinically significant PCa on mpMRI concerning histopathological components (i.e., cribriform component, intraductal pattern, or without cribriform component or intraductal pattern) were investigated. The clinically significant PCa foci with PI-RADS score <3 was accepted as an invisible lesion on mpMRI. ResultsIn all, 58 men with a total of 112 clinically significant PCa foci, were enrolled in the study. The intraductal pattern, cribriform pattern, or none of these patterns were observed in 28/112 (25 %), 43/112 (38.05 %), and 41/112 (36.60 %) tumor foci. Six out of 28 (21.42 %), 17/43 (39.53 %), and 18/41 (42.8 %) foci with an intraductal pattern, cribriform component, or without any of them, respectively, were invisible on mpMRI (P = 0.111). ConclusionThough it was not reached a statistical significance, clinically significant PCa with the cribriform component and without any intraductal or cribriform component are more likely to manifests mpMRI invisible foci than the intraductal pattern. Further multi-center studies are warranted to precisely elucidate mpMRI features of PCa regarding histopathological composition.

Cribriform-Morular Thyroid Carcinoma Is a Distinct Thyroid Malignancy of Uncertain Cytogenesis.

Tumors with papillary cribriform and morular architecture were initially considered to be variants of papillary thyroid carcinoma; however, recent observations have challenged this view. In this study, we reviewed the demographical, histopathological, and immunohistochemical features of the largest case series, consisting of 33 tumors. The age at time of pathological diagnosis ranged from 18 to 59 (mean 33) years, and all patients except one were female. Sixteen patients had multifocal and fifteen had unifocal disease. The status of focality was unavailable in two patients.Tumors were well-circumscribed, ranging in size from 0.1 to 8.0cm. The cribriform component was admixed with morulae in the majority, except seven had a cribriform-predominant architecture and two had predominantly solid growth. Variable degrees of nuclear enlargement, elongation, overlapping, and grooves were seen but florid nuclear convolution, intranuclear pseudoinclusions, and optically clear nuclei due to chromatin margination were not appreciated. There was no or little colloid material within the cribriform spaces. Two solid tumors had high-grade features. Immunohistochemical studies showed beta-catenin nuclear and cytoplasmic positivity in all cases. The cribriform component was positive for TTF1 and negative for thyroglobulin. PAX8 was absent in half of these tumors and focal in the remainder. Morulae were positive for keratin 5 and CD5 and negative for p63, p40, TTF1, and PAX8. Molecular studies revealed germline APC mutations in 12 tumors and were negative in 5 sporadic tumors in a subset of tested tumors. Irrespective of the antibody used in this cohort, all cribriform-morular carcinomas express TTF1; however, PAX8 immunoreactivity is weak, focal or negative, and all tumors lack thyroglobulin reactivity; these findings raise questions about tumor cell origin and may indicate that these are not of thyroid follicular epithelial differentiation. We postulate that morulae may represent divergent thymic/ultimobranchial pouch-related differentiation. Given their unique cytomorphology, immunohistochemical profiles, and genetic features that have little overlap with traditional follicular cell-derived thyroid carcinomas, we propose that these tumors represent a distinct form of thyroid carcinoma unrelated to other neoplasms of thyroid follicular cells.

A case of cribriform carcinoma of the skin: a newly described rare condition.

Primary cribriform carcinoma of the skin is an indolent, rare, adnexal tumor. Although its malignant potential remains uncertain, no recurrence or metastasis has been reported. A 33-year-old man presented with a solitary, erythematous, subcutaneous nodule on the right knee. The clinical impression was epidermal cyst, and the resected tumor demonstrated a well-circumscribed mass in the dermis and subcutis. The tumor was composed of two regions: a solid component and a cribriform component. The solid component (90%) showed multiple solid nests of epithelial cells. Individual cells had large, oval-to-round, hyperchromatic, pleomorphic nuclei with a nuclear groove. The cribriform component (10%) showed similar neoplastic cells with many prominent lumina. Some lumina had an eosinophilic substance that exhibited a positive periodic acid-Schiff reaction. No recurrence or metastasis was observed within a follow-up period of eight months after excision. In conclusion, we report the first case of primary cribriform carcinoma of the skin in Korea.

Characterization of Extracapsular Lymph Node Involvement and Its Clinicopathological Characteristics in Stage II–IIIA Lung Adenocarcinoma

The prognostic impact and clinicopathological characteristics of extracapsular lymph node involvement (ECLNI) in patients with surgically resected lung adenocarcinoma (LUAD) remain unknown in the context of the eighth edition N classification. We retrospectively reviewed 279 patients with stage II-IIIA LUAD who underwent lobectomy and lymphadenectomy. The correlations of ECLNI presence and clinicopathological profiles were analyzed. We also assessed the impact of ECLNI on the postoperative survival of pN1 and pN2 LUAD patients. ECLNI-positive status was more common in patients with high lymph node yield and in patients with multiple stations involved. The logistic regression model identified tumor spread through air spaces, micropapillary component, cribriform component, and nodal stage as predictive factors for ECLNI presence. LUAD patients with ECLNI presence had an increased risk of locoregional recurrence compared with those without (p < 0.001). Presence of ECLNI was confirmed as an independent risk factor for worse recurrence-free survival (RFS) (p < 0.001) and overall survival (OS) (p < 0.001) in the entire cohort. Among the 61 patients with ECLNI(+)pN2 disease, our analysis revealed that adjuvant radiation was a significant predictor of improved RFS and OS. In addition, ECLNI status provides additional precision in stratifying pN1 and pN2 patients with significantly different RFS and OS. Our data suggest that ECLNI remains a strong prognosticator of unfavorable OS and RFS for LUADs in the context of the eighth edition N classification. Adjuvant radiation should be actively considered for pN1b and pN2 LUAD patients with ECLNI presence.

Progress in Research on the Cribriform Component in Lung Adenocarcinoma

肺癌是全世界发病率最高的恶性肿瘤。目前，肺腺癌（lung adenocarcinoma, LUAD）是肺癌中最常见的组织学类型。然而，具有相同病理亚型的LUAD患者之间却存在显著的预后差异，导致该预后差异的主要原因之一是其组织学异质性。研究表明，除了2015年世界卫生组织（World Health Organization, WHO）对浸润性LUAD的5种主要生长方式的分类外，LUAD中还存在其他的组织学结构并影响其临床预后。其中，筛状成分（cribriform component, CC）是当前LUAD病理组织学的研究热点之一。已有研究表明，CC的有无可进一步预测LUAD患者的预后。随着相关研究逐渐深入，CC与LUAD各组织学类型、临床病理因素、生存预后等方面的关联尚存在争议。本文综合论述了CC在LUAD中的研究进展。

Characterization of lung adenocarcinoma with a cribriform component reveals its association with spread through air spaces and poor outcomes

ObjectiveTo further investigate the relationship between the cribriform component and spread through air spaces (STAS), and to unravel the potential pathological mechanism of poor prognoses in lung adenocarcinoma (LUAD) patients with a cribriform component. MethodsWe retrospectively reviewed the clinicopathological characteristics of 208 LUADs. The cribriform component was identified by hematoxylin and eosin staining. The identification of STAS referred to our previous study. The relationship between the cribriform component and STAS was determined by using a logistic regression model. The effects of the cribriform component and STAS on prognosis were analyzed using a Cox proportional hazards regression model. ResultsLUAD patients with a cribriform component had significantly inferior outcomes and increased risk of both locoregional and distant recurrences when compared with those with no cribriform component (p < 0.001). Among 67 patients with a cribriform component presented, 48 (71.6%) cases had STAS. The logistic regression model identified that the cribriform component was an independent risk factor for the presence of STAS (p = 0.044). Subgroup analysis showed that Crib+ (cribriform component present)/STAS+ (spread through air spaces positive) patients had significantly inferior outcomes when compared with Crib+/STAS- (spread through air spaces negative) patients (p < 0.001). Moreover, the multivariate Cox regression analysis further confirmed that STAS was an independent risk factor for a worsening recurrence-free survival (RFS) (p = 0.001) and overall survival (OS) (p < 0.001) in LUAD patients with a cribriform component. ConclusionsOur results indicated that STAS was more frequently observed in LUAD patients with a cribriform component. Moreover, STAS could provide helpful prognostic information in patients with stage I-III LUAD with a cribriform component.

Ampullary micropapillary adenocarcinoma widely metastatic to the lymph nodes: A case report

First described in breast cancer, invasive micropapillary carcinoma is being increasingly recognized as an aggressive histological variant of cancers arising from many different organs such as the urinary bladder, the lung, the colorectum, the stomach, the pancreatobiliary system and the salivary glands. Only a few reports exist that focus on the ampullo-pancreatobiliary region.We report a case of a 71 year old man who was admitted with symptoms of obstructive jaundice and slight epigastric pain and weight loss. Clinical and histological investigations revealed a small (<2 cm) ampullary adenocarcinoma comprised of an invasive front showing a micropapillary pattern, mixed with a biliary type solid and cribriform component. Extensive lymphatic and lymph node involvement were present. The widespread lymph node metastases affected both staging categories N and M.We believe micropapillary carcinoma should be considered in the WHO classification of Tumors of the Digestive System, in the ampullary chapter, as a separate histological subtype, in analogy with other organs to reflect its aggressive clinical behavior.

Human Epidermal Growth Factor Receptor 2 Status in Gastric Carcinomas with Distinctive Prevalent Cribriform Component.

Objectives A cribriform architectural pattern has been reported in 9% of one unselected consecutively collected series of gastric carcinomas (GC) with unfavourable prognostic outcome. Taking into consideration the biological relevance of the human epidermal growth factor receptor 2 (HER2) status, we have analyzed a cohort of GC with a cribriform component more than 40% (CGC) to evaluate the HER2 amplification rate as a potential target for therapy with trastuzumab. Results HER2 overexpression was encountered in 21 of 100 (21%) GC; a progressive increase in HER2 amplification was appreciated moving from non-CGC (20.6%) towards CGC cases (21.6%), although this difference does not reach a statistical significance. Nevertheless, either in univariate or in multivariate analyses, stage and HER2 status showed a significant p value (<0.001) in CGC patients. Conclusions Our data confirmed a worse prognosis in all CGC patients with HER2 amplification, resulting in a shorter survival time. We invite all pathologists in their daily practice to specify the occurrence of cribriform neoplastic component in GC, either in surgical or in bioptical samples, taking into practical assessment the high HER2 overexpression rate in order to correctly treat these patients with worse behavior.

Molecular, morphological and survival analysis of 177 resected pancreatic ductal adenocarcinomas (PDACs): Identification of prognostic subtypes

Pancreatic ductal adenocarcinoma (PDAC) has generally a poor prognosis, but recent data suggest that there are molecular subtypes differing in clinical outcome. This study examines the association between histopathologic heterogeneity, genetic profile, and survival. Tumor histology from 177 resected PDAC patients with follow-up data was subclassified according to predominant growth pattern, and four key genes were analyzed. PDACs were classified as conventional (51%), combined with a predominant component (41%), variants and special carcinomas (8%). Patients with combined PDACs and a dominant cribriform component survived longer than patients with conventional or other combined PDACs. Genetic alterations in at least two out of four genes were found in 95% of the patients (KRAS 93%, TP53 79%, CDKN2A/p16 75%, SMAD4 37%). Patients with less than four mutations survived significantly longer (p = 0.04) than those with alterations in all four genes. Patients with either wildtype KRAS or CDKN2A/p16 lived significantly longer than those with alterations in these genes (p = 0.018 and p = 0.006, respectively). Our data suggest that the number of altered genes, the mutational status of KRAS and certain morphological subtypes correlate with the outcome of patients with PDAC. Future pathology reporting of PDAC should therefore include the KRAS status and a detailed morphological description.

Clinicopathologic features of adenoid cystic carcinoma of breast

Objective: To investigate the clinicopathologic features and grading of adenoid cystic carcinoma (ACC) of the breast. Methods: Sixteen cases of ACC of the breast were analyzed and graded according to the previous report. Immunohistochemical (IHC) staining was used to detect the immunophenotype, Ki-67 proliferative index and expression of EZH2, and the association with tumor grade and outcome was analyzed. Results: Of the 16 cases, 11 were grade Ⅰ, with the epithelial and myoepithelial cells being arranged into tubular and cribriform structure with no solid component; three were grade Ⅱ, which were composed of mixed tubular, cribriform and solid component (<30%); and two were grade Ⅲ, which showed mainly solid component (>90%) and the tumor cells showed basaloid features with scanty cytoplasm and hyperchromatic nuclei, and mitotic count was>5/10 HPF. Immunophenotypically, the epithelial cells expressed CK7, CK8/18 and CD117; the myoepithelial cells expressed p63 and CK5/6; while the basaloid cells were positive for CK5/6 and CD117.Tubular and cibriform ACC showed low Ki-67 and EZH2 expression, while the two cases of solid variant with basaloid features showed high level of Ki-67 and EZH2 expression. Follow-up data were available in 13 cases with a median follow-up period of 42 months. Lung metastasis occurred after 12 months in one grade Ⅱ case and the patient died of disease after 34 months. Vertebral metastasis occurred after 12 months in one grade Ⅲ case and axillary lymph node metastasis occurred in another grade Ⅲ case. All other patients were free of disease at the end of the follow-up periods. Conclusions: ACC shows morphologic spectrum varying from low to high grade, the latter can may give rise to local and distant metastasis. ACC should not be regarded simply as low malignant potential, and should be graded for optimal treatment.

Mixed Gastric Carcinoma With Intestinal and Cribriform Patterns

Gastric adenocarcinoma is characterized by marked heterogeneity at cytological and architectural level and frequently shows overlap between microscopic patterns. This article describes a peculiar pattern of gastric adenocarcinoma, previously unreported, that combines intestinal type adenocarcinoma with areas of cribriform pattern that resembles both architectural and cytological in situ ductal carcinoma of the breast and to the best of the authors' knowledge, there are no earlier reports of this pattern in the stomach, which has been named "gastric carcinoma with cribriform component (CGA). The authors analyzed 12 cases of intestinal type adenocarcinoma with areas at least 20% of cribriform pattern (range from 20% to 90%) that was present in 9% of intestinal type gastric adenocarcinomas in their institution. There is slight predilection for male sex, and the median age of presentation is 55.8 years. The phenotype by immunohistochemistry is the same as with conventional (non-CGA) carcinomas. CGA shows more frequent lymphovascular invasion (P = .039), perineural invasion (P = .027) and resembles both in situ and invasive cribriform carcinoma of the breast. In clinical stage III the overall 3-year survival of CGA was worse than those with non-CGA component (38.6% vs 25%; 3-year survival, P = .010) and proves to be an independent adverse factor for overall survival in a multivariate analysis. Compared with conventional gastric carcinomas, CGA is deep infiltrating, has more nodal metastases, more lymphovascular and perineural invasion, and has decreased overall survival. Thus, proper recognition and report is important, even in small biopsies or small foci.

Pathology Quiz Case 1

A 66-YEAR-OLD WOMAN PRESENTED FROM AN outside institution 1 week after undergoing an aborted thyroidectomy for locally aggressive cancer of the thyroid gland. Intraoperative findings were notable for extrathyroid extension involving the right cricotracheal complex and encasement of the right recurrent laryngeal nerve, which was sacrificed. She did report childhood exposure to radiation, presumably for treatment of acne. There was no palpable residual thyroid or lateral neck disease on physical examination. Flexible fiberoptic laryngoscopy demonstrated a paretic right true vocal cord. A finecut computed tomogram of the neck demonstrated softtissue density fullness of the subglottic larynx, which was consistent with either tumor invasion of the airway or postoperative edema (Figure 1). In the operating room, a firm submucosal soft-tissue fullness was identified on endoscopy. Findings from a biopsy confirmed malignancy, showing cribriform and glandular architecture composed of squamoid, mucous, and intermediate cell types beneath an unremarkable respiratory epithelium. The patient underwent a total laryngopharyngectomy withacompletionthyroidectomy,bilateralparatrachealnode dissection,andacomprehensiverightneckdissection.Gross examination of the surgical specimen showed an infiltrative tumorarisingwithin the thyroidgland,withextension to the larynx, esophagus, and anterior strap muscles. The tumor demonstrated a complex histologic picture, with a gradual transition of 2 distinct types of cancer: a low-grade carcinomawithcribriformarchitectureandacarcinomaof papillary architecture and follicles containing brightly eosinophilic colloid material. The cribriform component of the tumor infiltrated ossified thyroid cartilage (Figure2) andanterior strapmusculature.Both thecribriformandthe papillary components showed mildly enlarged nuclei with irregular nuclear contours, nuclear grooves (Figure 3), and scattered intranuclear cytoplasmic pseudoinclusions. Metastatic foci of each tumor were present within numerous cervical lymph nodes. Immunohistochemical staining was positive for thyroid transcription factor 1 and thyroglobulin in both components of the tumor, although only amicroscopicfocusstainedpositively inthecribriformareas (Figure 3, inset). Staining showed strong positivity for p63 inthecribriformportion.StainingforKi-67andp53revealed a low degree of nuclear positivity ( 5%), consistent with a low-grade tumor. What is your diagnosis? Figure 1.

Intracystic invasive papillary carcinoma of the male breast with analyses of loss of heterozygosity on chromosome 16q

A 64-year-old man noticed a right subareolar mass in May 2005. On physical examination, an oval-shaped, well-circumscribedthe tumor (6.0 x 5.5 cm in size) was located just beneath the right nipple. The tumor was elastic, firm and freely movable. Neither axillary nor supraclavicular lymph nodes were palpable. Mammography demonstrated a 5 x 5-cm, relatively distinct and dense mass without microcalcifications or spiculations. There were no findings of concurrent gynecomastia. Ultrasonography revealed a large multilocular cyst with a mural hypoechoic protruding lesion exhibiting wide-based morphology with an irregular margin. On contrast-enhanced computed tomography, the inner lesion enhanced, but direct invasion of the tumor to the major pectoral muscle was not found. An intracystic papillary lesion, possibly papillary carcinoma, was suspected. In December 2007, wide excision of the tumor was performed. On histopathological examination, the tumor had a papillary pattern with a small cribriform component in the cystic wall with microinvasion of the stroma. Marginal status was negative. The final diagnosis of the disease was a microinvasive intracystic papillary carcinoma of low grade without axillary lymph node metastases. Immunohistochemically, estrogen receptor and progesterone receptor were both positive, but negative for HER-2 protein. No LOH on 16q could be detected. The prognosis of the disease was unclear; however, the malignant potential of this condition may be more clearly determined by studying the LOH on chromosome 16q.

Report on a Case of Pure Cribriform Carcinoma of the Breast with Internal Mammary Node Metastasis: Description of the Case and Review of the Literature

Pure ductal invasive carcinoma of the breast is more frequently associated with lymphatic invasion, lymph node involvement and high malignant histological grade than combined forms of breast carcinoma. Internal mammary node metastases are not frequently detected when the axillary nodes are negative. We report our experience of a case of pure cribriform carcinoma, associated with an intraductal cribriform component, in which the sentinel axillary nodes were negative, while nodal and perinodal metastasis was detected in one internal mammary lymph node. Data from the literature show that positive internal mammary nodes are an unusual finding when the axillary sentinel node is negative, especially in cases of cancer with a relatively good prognosis, such as cribriform cases.

Ductal carcinoma in situ of the male breast. Analysis of 31 cases.

From 1970 to 1992, 31 pure ductal carcinoma in situ (DCIS) of the male breast treated in 19 French Regional Cancer Centres were reviewed. They represent 5% of all breast cancers treated in men in the same period. The median age was 58 years, but 6 patients were younger than 40 years. TNM classification (UICC, 1978) showed 12 T0 (discovered only by bloody nipple discharge), 10 T1, 5 T2 and four unclassified tumours (Tx). 11 patients (35.5%) had clinical gynecomastia, and three (10%) had a family history of breast cancer. 6 patients underwent lumpectomy, and 25 mastectomy. Axillary dissection was performed in 19 cases. 6 cases received postoperative irradiation. 15 out of 31 lesions were of the papillary subtype, pure or associated with a cribriform component. The size of the 12 measured lesions varied from 3 to 45 mm. All lymph nodes sampled were negative. With a median follow-up of 83 months, 4 patients (13%) presented a local relapse (LR), respectively, at 12, 27, 36 and 55 months. 3 of these patients had been initially treated by lumpectomy. In one case LR was still in situ, but already infiltrating in the 3 others. Radical salvage surgery was performed in 3 cases, but one patient developed metastases and died 30 months later. The last patient was treated by multiple local excisions and tamoxifen. One 43-year-old patient developed a contralateral DCIS and three others developed a metachronous cancer. The aetiology and risk factors of male breast cancer remain unknown. Gynecomastia, which implies an imbalance between androgen and oestrogen, may be a predisposing factor. As in women, DCIS in the male breast has a good prognosis. Total mastectomy without axillary dissection is the basic treatment. Frequently, the first symptom is a bloody nipple discharge. The age of occurrence is younger than for infiltrating carcinoma, suggesting that DCIS is the first step in the development of breast cancer.

An immunohistochemical study of adenoid cystic carcinoma of the external auditory canal.

Specimens from five cases of adenoid cystic carcinoma of the external auditory canal were studied by immunohistochemical staining, and findings were compared with those from adjacent non-neoplastic tissues containing ceruminous glands. In the ceruminous gland, cytokeratin showed diffuse positive staining, while myoepithelial cells were stained for smooth muscle actin, desmin, S-100 protein and vimentin. The epithelial markers used were cytokeratin, carcinoembryonic antigen and secretory component and stained at various densities the inner cells of the tubular component and duct-lining cells in the cribriform component of tumor tissues. In contrast, the muscular markers, smooth muscle actin and desmin, and the mesenchymal marker, vimentin, were positive in the outer cells of the tubular component and in the cyst-lining cells of the cribriform component. S-100 protein immunoreactivity showed paradoxical results; positive findings occurred in the myoepithelial cells of the ceruminous glands and in the inner cells of the tubular component and duct-lining cells of the cribriform component of the tumor. Present findings demonstrate that adenoid cystic carcinoma of the external auditory canal had dual epithelial and myoepithelial differentiation and can mimic the ceruminous glands of the auditory canal.