MORPHOLOGICAL LESIONS OF THE PANCREATIC DUCTS

Morphological lesions of the pancreatic ducts were studied in 113 control autopsy cases, and 84 cases of primary pancreatic carcinoma. The lesions were classified into pyloric gland metaplasia, focal pseudo-proliferation, goblet cell metaplasia, squamous metaplasia, and atypical proliferation. Diabetes mellitus or glycosuria, alcohol intake, and smoking do not seem to have any close associations with these lesions or pancreatic carcinoma. Pyloric-gland and squamous metaplasias were found at nearly comparable incidences both in control and carcinoma cases, but marked atypical proliferations, which were indistinguishable from carcinoma in situ or intraductal spreading of carcinoma, were more frequently observed in the carcinoma cases. Pyloric gland metaplasia was the most common among the various lesions, and considered to represent nonspecific change of the pancreatic duct. However, it was suggested that some of the metaplastic lesions might be transformed into atypical proliferations and further into carcinoma in situ. The expected latent period from the appearance of in situ lesion to overt pancreatic carcinoma may be a clue to early diagnosis and effective surgical treatment, but possible multiplicity of carcinoma in situ or intraductal spreading of carcinoma even at its early stage will burden further problems on its treatment. On rare occasions, argyrophil cells were found In the pyloric gland metaplasia, and its significance was discussed in relation to the genesis of Zollinger-Ellison tumor.     

Expression of androgen receptors and inhibin/activin alpha and betaA subunits in breast apocrine lesions

The importance of androgens and their receptors inhibin and activin remains unknown for mammary epithelial cells. We investigated the role of these hormones in breast apocrine lesions (BAL) using immunohistochemistry to study androgen receptors (AR) and the inhibin/activin alpha and betaA subunits. Forty-two cases of BAL were evaluated, including 22 cases of fibrocystic disease (FCD) showing prominent apocrine changes, 10 intraductal papillomas with extensive apocrine metaplasia, 5 cases of apocrine carcinoma in situ (CIS), and 5 cases of apocrine carcinoma. Fifty non-apocrine lesions were included as controls: 20 cases of FCD, 5 cases of DCIS, and 25 cases of invasive ductal carcinoma. AR was more frequently expressed in BAL than in non-apocrine lesions (p=0.001). AR expression was not related to tumor progression. AR showed a significant positive correlation with betaA subunits (r=0.832, p<0.001), and an inverse correlation with alpha subunits (r=-0.233). The alpha and betaA subunits demonstrated a significant inverse correlation with each other (r=-0.271, p=0.0048). As the expression of the alpha and betaA subunits reflects inhibin and activin A, respectively, AR and activin A may be implicated in apocrine morphogenesis, but not in tumor progression.     

Morphological lesions of the pancreatic ducts. Significance of pyloric gland metaplasia in carcinogenesis of exocrine and endocrine pancreas

Morphological lesions of the pancreatic ducts were studied in 113 control autopsy cases, and 84 cases of primary pancreatic carcinoma. The lesions were classified into pyloric gland metaplasia, focal pseudo-proliferation, goblet cell metaplasia, squamous metaplasia, and atypical proliferation. Diabetes mellitus or glycosuria, alcohol intake, and smoking do not seem to have any close associations with these lesions or pancreatic carcinoma. Pyloric-gland and squamous metaplasias were found at nearly comparable incidences both in control and carcinoma cases, but marked atypical proliferations, which were indistinguishable from carcinoma in situ or intraductal spreading of carcinoma, were more frequently observed in the carcinoma cases. Pyloric gland metaplasia was the most common among the various lesions, and considered to represent nonspecific change of the pancreatic duct. However, it was suggested that some of the metaplastic lesions might be transformed into atypical proliferations and further into carcinoma in situ. The expected latent period from the appearance of in situ lesion to overt pancreatic carcinoma may be a clue to early diagnosis and effective surgical treatment, but possible multiplicity of carcinoma in situ or intraductal spreading of carcinoma even at its early stage will burden further problems on its treatment. On rare occasions, argyrophil cells were found in the pyloric gland metaplasia, and its significance was discussed in relation to the genesis of Zollinger-Ellison tumor.     

Atypical apocrine metaplasia in sclerosing lesions of the breast: a study of 51 patients

Sclerosing breast lesions with cytologically atypical apocrine metaplasia present a difficult diagnostic problem. The clinical significance of these lesions has not been established although, historically, apocrine metaplasia and sclerosing adenosis have been regarded as totally benign. To further assess these lesions, we studied 51 patients with atypical apocrine metaplasia in sclerosing lesions of the breast, obtaining an average follow-up of 35 mo (12 to 76 mo). For convenience, these have been grouped together as atypical apocrine sclerosing lesions (AASL). The average age at diagnosis was 58 yr. The lesions tended to be small (67% less than 1.0 cm) and usually were detected by mammography (78%). Four patients had an ipsilateral mastectomy following a biopsy of AASL that was interpreted as carcinoma or "precancerous" by the referring pathologist. Two patients had nonapocrine intraductal and infiltrating duct carcinoma in previous contralateral mastectomy specimens. None of the 47 women with an intact breast developed breast carcinoma during the follow-up period. Immediate treatment with surgery and/or radiation is not indicated. The long-term clinical implication of these lesions is yet to be determined; therefore, continued clinical observation of AASL patients is advisable.     

Simple mucin-type carbohydrate antigens (T,sialosyl-T,Tn and sialosyl-Tn) in breast carcinogenesis

Immunohistochemical analysis of the expression of simple mucin-type carbohydrate antigens (Tn, sialyl-Tn and T) was performed in a series of 43 cases of intraductal hyperplasia without atypia, 9 cases of intraductal hyperplasia with atypia, 54 cases of ductal carcinoma in situ (DCIS) and 26 cases of invasive breast carcinoma. We also studied 36 cases of isolated breast normal epithelium, 20 cases of normal breast epithelium adjacent to neoplasms and 14 cases of apocrine metaplasia. All antigens were detected in different frequencies in normal, hyperplastic, metaplastic and neoplastic breast epithelium. Tn and sialyl-Tn are expressed more frequently in malignant than in benign breast epithelium; while Tn expression increases from normal to invasive carcinomas, sialyl-Tn increases until DCIS and drops in invasive carcinomas, suggesting that either there is a failure of a proportion of DCIS to progress to invasive carcinoma or loss of expression of sialyl-Tn when some carcinomas become invasive. The high frequency of Tn and sialyl-Tn expression in breast intraductal proliferations probably reflects incomplete glycosylation in these lesions, which is a well-known tumour-associated phenomenon and supports the assumption that such lesions are putative precursors of breast cancer. T antigen was expressed in all groups studied, but its prevalence differed significantly between normal and neoplastic epithelium. The expression of these antigens in epithelium adjacent to carcinomas is similar to that found in isolated normal breast epithelium, whereas apocrine metaplasia has a pattern of simple mucin-type glycosylation that is specific and distinct from that of the normal breast epithelium, with a high frequency of marked expression of Tn and sialyl-Tn. The similarity of the pattern of expression of simple mucin-type antigens in metaplasia and malignant neoplasia reduces the usefulness of these markers from a diagnostic standpoint.This work was supported in part by a grant (no. 201240/92) from the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Brazil     

Fine needle aspiration cytology of invasive micropapillary carcinoma of the breast

AIM: To determine the pathognomonic diagnostic cytological features of invasive micropapillary carcinoma of the breast which is a poor prognostic subtype of infiltrating ductal carcinoma. METHODS: A series of 20 histologically proven tumours were reviewed retrospectively to evaluate the various cytological features, including tumour morules, isolated malignant cells, staghorn epithelial structures, mucinous background and apocrine metaplasia. RESULTS: Tumour morules formation and isolated malignant cells were the two most reliable and constant cytological features, being present in 75% (15/20 cases) of cases. Staghorn epithelial structures were present in 35% (7 cases). Mucinous background (2 cases, 10%) and apocrine metaplasia (4 cases, 20%) of the tumour cells were seen in a few cases only and did not appear very helpful. CONCLUSION: Tumour morules formation, isolated malignant cells and staghorn epithelial structures are the most reliable cytological features, and the presence of these should raise suspicion of invasive micropapillary carcinoma.     

Metaplastic breast carcinoma on fine-needle cytology samples: a report of three cases

Metaplastic breast carcinoma (MBC) may have a varied presentation on fine-needle cytology samples. We herewith describe three cases of MBC found in our series. One of these cases showed a peculiar mixture of malignant ductal, apocrine type, and squamous epithelial cells with fascicles of spindle cells with variable degree of atypia and was diagnosed as metaplastic carcinoma of the carcino-sarcomatous type. The other two lesions were characterized by an abundant chondroid extracellular matrix to which were variably admixed carcinomatous and chondroid-type cells, with variable degree of atypia. Both these latter cases were defined as matrix-producing metaplastic carcinomas. Because of the various presentation of MBC on fine-needle cytology samples and the possible influence of needle "sampling" on the cytological specimen, the spectrum of differential diagnoses to be considered may encompass a number of benign and malignant entities, like keratinous subareolar cysts, malignant fibroepithelial lesions with myxo-chondroid stroma, and true sarcomas of the breast, with cartilaginous metaplasia. It is the Authors' feeling that, with optimal samples, the cytomorphological findings of this rare variant of breast carcinoma permit its accurate pre-operative diagnosis.     

Apocrine change in fine-needle aspiration biopsy: nuclear morphometry and DNA image cytometry

The aim of this study was to investigate the potential of computerized nuclear morphometry and DNA image cytometry in characterizing the apocrine change of mammary epithelium in fine-needle aspiration biopsy (FNAB). The effect of two different sample processing techniques on the results was also studied. Mean nuclear areas in air-dried smears ranged from 59.0 microm2 to 151.0 microm2 and in ethanol-fixed samples from 32.3 microm2 to 63.4 microm2. The DNA histograms of apocrine cells usually showed a dominant peak in the diploid region. In some cases the mode of the peak was slightly shifted to the right or left in respect to the control peak. One case had a tetraploid cell population, suggesting atypical apocrine change. After histological investigation this case was diagnosed as infiltrating carcinoma. The patient had earlier been treated with x-ray irradiation for a mediastinal lymphoma. Findings of nuclear morphometry and DNA cytometry in apocrine metaplasia are here described in a systematic study for the first time. The data suggest that these methods may help in distinguishing premalignant and malignant apocrine lesions from typical apocrine metaplasia of mammary epithelial cells.     

腮腺硬化性多囊性腺病临床病理分析

目的探讨腮腺硬化性多囊性腺病（SPCA）的临床病理特征和预后。方法报道1例腮腺SPCA,做HE和免疫组化染色,结合文献对该病的临床表现、病理形态特点及预后进行探讨。结果患者女性,29岁,发现左腮腺无痛性结节状瘤样肿块1年。组织学上类似于纤维性囊性乳腺病。镜下见病变以大片玻璃样变性的硬化的胶原组织为背景,包埋入囊性扩张的导管,形成不规则、模糊的小叶结构。导管上皮有的呈大汗腺样化生,有的胞质内含丰富、粗大的强嗜伊红酶原颗粒,有的呈泡沫细胞样外观。导管可见上皮增生及结构不良。结论SPCA应纳入大涎腺肿瘤的鉴别诊断之中。目前对该病的自然病程和确切的复发率尚不清楚,同时鉴于已有SPCA伴发导管原位癌的报道,因此患者术后应密切随访。     

Axillary apocrine carcinoma with benign apocrine tumours: a case report involving a pathological and immunohistochemical study and review of the literature

BACKGROUND: Apocrine carcinoma is rare and often occurs in the axilla. This is the second apocrine carcinoma arising in bilateral axillae with associated apocrine hyperplasia to be reported. AIMS/METHODS: Because benign apocrine tumours may be precursors of cancer, this case was investigated immunohistochemically and histologically, and a literature (English and Japanese) review undertaken of cases with coexistent malignant and benign apocrine tumours in the axilla to elucidate the relation between apocrine carcinoma and benign apocrine tumours. RESULTS: Only four cases of axillary apocrine carcinoma with benign apocrine tumours were identified in the literature. In each case, benign apocrine hyperplasia was situated within and surrounding the adenocarcinomatous nests. Staining for epithelial membrane antigen revealed three patterns: (1) poorly differentiated tumour cells showing strong cytoplasmic staining; (2) combined luminal surface and cytoplasmic staining of glandular cells; and (3) a strongly positive lineal staining pattern at the luminal membrane surface, comprising one or two apocrine hyperplastic secretory cells. The basal lesions of apocrine hyperplasia were strongly positive for alpha smooth muscle actin, whereas the periphery of adenomatous lesions showed weaker positive staining, even though the periphery of adenocarcinomatous lesions was negative. CONCLUSIONS: All five apocrine carcinomas with benign apocrine tumours occurred in elderly Japanese men who had bilateral benign apocrine tumours even if affected by unilateral axillary apocrine carcinoma. The immunohistochemical results support the notion that apocrine hyperplasia is a precursor of cancer and that apocrine carcinoma, adenoma, and hyperplasia may be successive steps in the linear progression to carcinoma.     

Loss of heterozygosity in fibrocystic change of the breast: genetic relationship between benign proliferative lesions and associated carcinomas

Loss of heterozygosity (LOH), a genetic change frequently detected in cancer, can also occur in benign epithelial foci in the breast. To characterize LOH in benign breast tissue, 32 cases containing the various components of fibrocystic change in the absence of malignancy were studied. Microdissected foci of ductal hyperplasia, apocrine metaplasia, sclerosing adenosis, and morphologically normal terminal duct lobular units (TDLUs) were analyzed for LOH at 14 polymorphic loci representing seven chromosomal arms. LOH was detected in 22% of normal TDLUs (6/27), 17% of adenosis (4/23), 19% of hyperplasia (4/21), and 53% of apocrine metaplasia (10/19) specimens. Because of the high percentage of LOH in apocrine metaplasia in nonneoplastic specimens, the genetic relationship between apocrine metaplasia and cancer was studied in a panel of breast cancer cases. Of 14 examples of apocrine metaplasia adjacent to a carcinoma, seven were found to have LOH with at least one marker. In all seven cases, the tumor and apocrine metaplasia shared LOH at one or more markers. The results demonstrate that LOH occurs frequently in the components of fibrocystic change as well as in normal TDLUs and suggest that foci of apocrine metaplasia can share a genetically altered precursor cell with an associated carcinoma.     

Apocrine adenosis: a precursor of aggressive breast cancer?

AIM--To investigate overexpression of c-erbB2, expression of the p53 protein product and proliferation rates in benign breast lesions with specific reference to apocrine adenosis. METHODS--Twenty one cases of apocrine adenosis were stained with monoclonal antibodies to p185, the protein product of the c-erbB2 oncogene, the protein product of the p53 tumour suppressor gene and to the cell cycle related protein Ki67. Three cases were associated with concomitant ductal carcinoma in situ of large cell type and two were associated with invasive tubular or cribriform carcinoma. RESULTS--Twelve (57.1%) cases showed membrane staining for c-erbB2 oncoprotein of apocrine cells within sclerosing adenosis and six (28.6%) had occasional p53 protein positive cells. One case not associated with carcinoma showed extensive staining of apocrine metaplasia outside the area of apocrine adenosis. The proliferation rate, as measured by Ki67 staining, was increased in some of the lesions and all lesions showed at least some of the cells to be in the cell cycle. CONCLUSIONS--The expression of abnormal oncogene products and increased proliferation in some of these apocrine lesions questions the supposed degenerative nature of the atypia seen in such cases and suggests that there may be an association between these lesions and large cell ductal carcinoma in situ and hence invasive carcinoma.     

The enigmatic nature of apocrine breast lesions

Epithelial cells of fetal breast glandular structures, at the third trimester of pregnancy (28 weeks), produce GCDFP-15, in the absence of specific apocrine morphology. Apocrine epithelium of the breast may be a normal process of differentiation rather than a result of metaplasia, and it has been demonstrated that it is estrogen-receptor, progesterone-receptor and bcl-2 negative, but androgen-receptor (AR) positive. The significance of AR expression in apocrine epithelium is uncertain. Apocrine epithelium is seen in a wide spectrum of breast entities, ranging from benign lesions to invasive carcinoma. Breast cancer accounts 32% of all cancer cases among women and is the most common type of cancer in women. Little is known about breast carcinogenesis. Widely, it is accepted that breast cancer, like most other type of cancer, is being developed through the accumulation of genetic aberrations. Apocrine epithelium may reflect instability of the breast epithelium, creating an environment favouring further oncogenic alterations. In the last decade, several lines of evidence support the idea that some breast benign epithelial apocrine lesions are clonal lesions and may be considered as truly pre-malignant or precursors of breast carcinoma. Apocrine changes in many cases do not present any diagnostic difficulty; on the other hand, apocrine proliferations with cytologic atypia can be particularly difficult and challenging. The purpose of this study is to collect and highlight the areas of consensus in the literature as well as the controversial areas concerning the apocrine epithelium of the breast.     

Eccrine ductal and acrosyringeal differentiation of the breast epithelium—a lesion associated with some metaplastic breast carcinomas

Two cases of metaplastic breast carcinoma associated with eccrine ductal metaplasia in the surrounding breast tissue are reported. The metaplastic epithelium deviated from the normal in its immunophenotype not expressing glandular cytokeratins (Cam 5.2) and estrogen receptors, being maspin-positive, and resembling morphologically different segments of dermal eccrine duct and acrosyringium. In addition, in one of the cases, basalioma-like intraductal cell proliferation was observed, also showing focal acrosyringeal differentiation. The invasive carcinomas, one of them representing “syringomatous squamous tumor of the breast” while the other diagnosed as high-grade metaplastic carcinoma, also showed focal eccrine and acrosyringeal differentiation and intensive diffuse maspin expression. These previously unrecognized metaplastic changes of the breast epithelium may represent precursor lesions of certain types of metaplastic breast carcinomas.     

Carcinoma ex pleomorphic adenoma with special reference to the prognostic significance of histological progression: a clinicopathological investigation of 41 cases

Weiler C, Zengel P, van der Wal J E, Guntinas‐Lichius O, Schwarz S, Harrison J D, Kirchner T & Ihrler S
(2011) Histopathology 59 , 741–750 Carcinoma ex pleomorphic adenoma with special reference to the prognostic significance of histological progression: a clinicopathological investigation of 41 cases Aims: To investigate a large series of cases of carcinoma ex pleomorphic adenoma (CEPA) to determine prognostic factors. Methods and results: Thirty cases of CEPA associated with primary pleomorphic adenoma (PA) and 11 cases of CEPA associated with recurrent PA were investigated. The median follow‐up was 57.7 months, and ranged from 4 to 156 months. Purely intraductal carcinoma was found in 15 cases. Intraductal and extraductal intracapsular carcinoma together was found in one case. Extracapsular carcinoma was found in 25 cases. Prognosis was good for CEPA that was purely intraductal, extraductal intracapsular, or up to 5 mm extracapsular, and poor for CEPA that was 8 mm or more extracapsular. There were relatively more cases of CEPA with extracapsular invasion of 8 mm or more from recurrent PA than from primary PA, and the prognosis for CEPA associated with recurrent PA was worse than that for CEPA associated with primary PA. Conclusions: The threshold for distinguishing minor extracapsular invasion with good prognosis from wide extracapsular invasion with poor prognosis is 5 mm. The worse prognosis for CEPA associated with recurrent PA indicates the necessity for close surveillance of patients with recurrent PA.     

The significance of atypical apocrine cells in fine-needle aspirates of the breast

Apocrine metaplastic cells are frequently present in fine-needle aspirates (FNAs) of breast lesions, especially fibrocystic disease. Occasionally, apocrine cells may be atypical and present diagnostic difficulties. The morphologic features of six breast FNAs that contained atypical apocrine cells in breast aspirates. In the six abnormal cases, the large, pleomorphic, atypical apocrine cells were the predominant cell type and occurred singly and in syncytial tissue fragments. The cells had large, eccentric, vesicular nuclei and usually multiple macronucleoli. The histologic diagnoses in the cases were apocrine carcinoma (five cases) and atypical apocrine metaplasia (one case). In comparison, benign apocrine cells are relatively small and uniform and arranged in cohesive, orderly sheets. It is concluded that, in breast FNAs, the predominance of atypical apocrine cells, occurring singly and in syncytia, should raise the suspicion of carcinoma.     

乳腺放射状硬化性病变的病理形态学观察

目的 探讨乳腺放射状硬化性病变的组织病理特点和鉴别诊断.方法 收集44例乳腺放射状硬化性病变,进行组织形态学和免疫组织化学SP法或EnVision二步法染色观察.结果 44例均发生在女性,年龄17～54岁(平均40.3岁).31例会诊者中13例误诊为癌.镜下病变呈放射状,中央为纤维瘢痕区,其内常有受压变形的腺管,周围有放射状分布的扩张腺管及不同程度增生的导管和小叶,可伴大汗腺、柱状细胞化生增生,其中14例见坏死,8例伴不典型导管增生.免疫组织化学染色显示纤维瘢痕组织内假浸润的变形腺管周围有肌上皮,旺炽性增生的上皮呈CK5/6阳性.结论 乳腺放射状硬化性病变有特殊的形态特点,易误诊为癌,需与导管内癌、小叶性肿瘤、小管癌、浸润性导管癌鉴别.     

CD44s as a surrogate marker for distinguishing intraductal papilloma from papillary carcinoma of the breast

BACKGROUND: It has been shown that CD44 variants are differentially expressed in normal and neoplastic breast tissues. The diagnostic value of these markers in distinguishing benign from malignant breast lesions has not been well examined. AIMS: To evaluate the diagnostic value of CD44s in distinguishing between intraductal papillomas and papillary carcinomas of the breast, which may be difficult morphologically. METHODS: Expression of CD44s detected by immunohistochemistry was studied in a series of intraductal papillomas (11) and papillary carcinomas (10). The normal breast tissues surrounding the lesions of these cases served as a control. The number of CD44s positive epithelial cells was scored and categorised as < 10%, 10-70%, or > 70%. RESULTS: Normal breast epithelial cells and all intraductal papillomas (11 of 11) expressed CD44s in a high proportion of cells (> 70%). In contrast, the majority of papillary carcinoma cases (eight of 10) expressed this marker in < 10% of the cells. In the remaining two papillary carcinoma cases, positivity was seen in more than 10% but still less than 70% of the cells. CONCLUSIONS: CD44s detection by immunohistochemistry is useful in distinguishing intraductal papillomas from papillary carcinomas of the breast.     

Pure intraductal carcinoma of the parotid gland: Cytologic findings on FNA sample. Report of one case

One case of intraductal carcinoma of the parotid gland in a 67‐year‐old male patient is here introduced. The patient, who had a one‐year history of a parotid mass, had undergone ultrasound and MRI examination that disclosed a 13x4x3 mm well delimited nodular mass of the accessory lobe of his left parotid gland. Ultrasound‐guided Fine Needle Aspiration (FNA) had been performed by the clinician. The obtained smears showed widespread cellular necrosis in which cellular clusters with moderate and focally severe atypias displayed papillary and cribriform architecture and were admixed with sheets of epithelial cells with less striking nuclear atypias, squamous, or apocrine metaplasia. Histopathological examination disclosed a pure intraductal carcinoma of the parotid gland with classical morphology, which was radically excised. The differential cytological diagnosis of pure intraductal carcinoma of salivary glands may be difficult and comprises mucoepidermoid carcinoma as well as “in situ” carcinomas developping in the context of sclerosing polycystic adenosis, mammary analogue secretory carcinoma (MASC) of the salivary glands and cystic variants of salivary adenocarcinoma NOS (formerly called cystadenocarcinomas).     

Fine-needle aspiration cytology of ductal adenoma: Report of a case associated with a mucocele-like lesion

Ductal adenoma (DA) is an uncommon breast lesion that can histologically and clinically mimic carcinoma. We performed a fine-needle aspiration (FNA) of a DA. Cytologically, the lesion had features overlapping with those of mucinous carcinoma (MC), mucocele-like lesion, lactating adenoma (LA), and in retrospect with intraductal papilloma (IP). The smears were highly cellular and contained numerous monolayered sheets of ductal cells with prominent punched-out, small vacuoles distending the cytoplasm. The nuclei were mostly round to oval and had bland chromatin. Occasionally cells with enlarged nuclei and conspicuous nucleoli were present. The background showed large mucin pools, scattered single cells with mild nuclear atypia, some with apocrine metaplasia, rare stripped nuclei, and a fibrovascular stromal component. Calcifications were also present. We compare our cytologic findings with those of the lesions considered in the differential diagnosis. Due to its rare incidence and unusual features, DA may represent a diagnostic pitfall on FNA. Increased awareness of its cytologic appearance may help prevent a misdiagnosis. © 1995 Wiley-Liss, Inc.