Cytologic findings in infiltrating micropapillary carcinoma and mucinous carcinomas with micropapillary pattern

OBJECTIVE: To examine the observation that some mucinous carcinomas have a micropapillary pattern and are mucinous variants of the highly angioinvasive infiltrating micropapillary carcinomas (IMPC). STUDY DESIGN: We evaluated cytologic findings of 13 IMPC and 55 mucinous carcinomas for comparative features. RESULTS: In mucinous carcinomas, 37 of 50 (74%) had a micropapillary pattern. This group included 27 cases with pure mucinous micropapillary morphology (MUMPC), 8 MUMPC associated with a ductal carcinoma of the IMPC type (MUIDC) and 2 cases of mixed mucinous carcinomas with an MUMPC and a solid variant ofpapillary carcinoma (SVPC) component. On cytology both IMPC and mucinous carcinomas with micropapillary pattern demonstrated the micropapillary pattern, that is, angulated clusters or abortive papillae and ball-like clusters. However, the IMPC smears revealed numerous singly scattered tumor cells and larger fragments with shrub-like branching and the MUMPC had psammoma bodies. The mixed MUMPC and SVPC showed the classic cytologic features of MUMPC admixed with abundant singly dispersed tumor cells in the background representing the SVPC component. CONCLUSION: Although IMPC and the MUMPC share the micropapillary pattern on histologic examination, mucin alters the appearances in aspirates. Recognition of this morphologic spectrum will help in understanding the behavior of these tumors.     

Fine needle aspiration cytologic findings of breast mucinous neoplasms: differential diagnosis between mucocelelike tumor and mucinous carcinoma

OBJECTIVE: To report the cytologic findings of mucocelelike tumor and mucinous carcinoma. STUDY DESIGN: All mucinous neoplasms diagnosed by fine needle aspiration and confirmed by histologic examination were reviewed to detect the cytologic findings helpful for the differentiation. The cytologic findings were correlated with the histologic findings. RESULTS: Cytologically, mucinous carcinomas were highly cellular and showed many single epithelial cells and variably formed epithelial cell clusters in abundant extracellular mucin. Malignant cells exhibited round, atypical nuclei; granular chromatin; and small nucleoli. Mucocele like tumor showed low cellularity with scanty, monolayered, small sheets of epithelial cells and abundant, extracellular mucin. Myoepithelial cells were present within the epithelial cell sheets. Tumor cells were usually small, with uniform, round nuclei; fine chromatin; and absence of nucleoli. CONCLUSION: Cytologic findings of mucocelelike tumor and mucinous carcinoma were different in cellularity, shape of cell clusters and nuclear features, although mucocelelike tumors having a carcinoma component were similar to mucinous carcinoma. Awareness of the cytologic findings of breast mucinous neoplasms is important to make a specific diagnosis.     

乳腺浸润性微乳头状癌的研究现状

乳腺浸润性微乳头状癌(IMPC)是乳腺浸润性癌的一种特殊类型,其发生率低,临床表现及影像学特征与普通的乳腺浸润性导管癌没有显著区别。这种病理类型可与普通浸润性导管癌混合出现,也可表现为单纯的浸润性微乳头状癌。但浸润性微乳头状癌具有独特的组织学形态及分子结构,决定了其病理学分级较高、易于发生淋巴结转移的侵袭性生物学行为特点。多数浸润性微乳头状癌在影像学上表现为边缘不清的不规则肿块影,常伴有微小钙化。其特征性病理形态为细胞膜上皮抗原(EMA)在肿瘤细胞簇外周的细胞和基质中腔隙边缘特异性染色,同时显微镜下瘤细胞表面发现微绒毛结构,说明了瘤细胞簇周围的空隙样结构实际上是管状腔隙,瘤细胞呈"极向倒转"方式排列。IMPC具有高度淋巴血管浸润倾向,局部复发率高,是一种预后较差的类型。本文对近年来关于乳腺浸润性微乳头状癌的研究进展进行了综述。     

Cribriform-morular variant of papillary thyroid carcinoma. Report of a case showing morules with peculiar nuclear clearing

BACKGROUND: There have been only 4 reported cases of cribriform-morular variant of papillary thyroid carcinoma (CMVPTC) with cytologic findings from fine needle aspiration. In these reports, the cytologic findings do not fully reflect the histologic characteristics of this entity. We report a case of CMVPTC in which a cribriform pattern without colloid and epithelial morules with peculiar nuclear clearing (PNC) were present in smears, thus fulfilling the criteria for a cytologic diagnosis of CMVPTC. Protein truncation tests for APC molecule abnormality indicated the presence of germline mutation in the patient's APC gene. CASE: A 30-year-old woman had multiple thyroid tumors. Aspiration cytology revealed a large number of round to spindle-shaped atypical-cells showing sheet-like, cribriform, follicular, whorl-like and solid, 3-dimensional arrangements. The cribriform and follicular arrangements did not contain colloid in the lumen. The powdery chromatin pattern characteristic of papillary carcinoma was not observed, but there were scattered intranuclear cytoplasmic pseudoinclusions and grooved nuclei. The nuclei of the atypical cells presenting in the whorl formations showed enlargement, thickened nuclear membranes and entirely clear contents, consistent with PNC. Hyalinelike necrotic cells were also observed in the cell clusters or in the background. Histologic and immunohistochemical findings were typical of CMVPTC. CONCLUSION: The cribriform pattern without colloid, fascicular or whorl formation of spindle cells, and morules with PNC are identifiable on cytologic smears and are sufficiently distinctive to allow a cytologic diagnosis of CMVPTC.     

Fine needle aspiration cytology of invasive micropapillary (pseudopapillary) carcinoma of the breast. Report of 11 cases with clinicopathologic findings

OBJECTIVE: To describe the cytologic features of invasive micropapillary carcinoma of the breast, a distinct, unusual variant of infiltrating duct carcinoma characterized histologically by pseudopapillary structures lacking fibrovascular cores and tubuloalveolar structures floating freely within clear spaces separated by a delicate fibrocollagenous stroma and characterized clinically by prominent lymphotropism and an aggressive clinical course. STUDY DESIGN: We reviewed the clinical, cytologic, histologic, immunohistochemical and flow cytometric features in 11 cases of invasive micropapillary carcinoma of the breast diagnosed preoperatively by fine needle aspiration. RESULTS: All patients were women, ranging in age from 31 to 83 years. A preoperative diagnosis of malignancy was made in all cases. Tumor size ranged from 1.2 to 5.5 cm. Ten patients had lymph node metastases. Cytology was characterized by a "dual" pattern formed by round or angulated, three-dimensional, cohesive clusters of neoplastic cells with pseudopapillary configuration and two-dimensional, dyscohesive aggregates and single cells with high grade nuclei and intact cytoplasm.     

Fine needle aspiration cytology of invasive micropapillary carcinoma of the breast. A case report

BACKGROUND: Invasive micropapillary carcinoma of the breast is uncommon and was characterized only recently. Awareness of this entity and its cytologic appearance is important to allow early diagnosis by fine needle aspiration cytology (FNAC). To our knowledge, only two cases of FNAC of this lesion have been reported in the English-language literature. CASE: An 80-year-old female presented with a firm, nontender mass in the upper outer quadrant of the left breast. FNAC showed ductal carcinoma, and mastectomy showed invasive micropapillary carcinoma. The patient had axillary metastases and received tamoxifen. CONCLUSION: The cytologic features of invasive micropapillary carcinoma are distinctive, with clusters of cells showing hyperchromatic, irregular and crowded nuclei and peripherally located cytoplasm with a rare central lumen. Fibrovascular cores are absent. Although FNAC experience with this lesion is limited, the characteristic cytologic features, including "inside-out" cell clusters, should raise the suspicion of this variant of ductal carcinoma. Differentiation from other papillary lesions and malignancies may be possible, but more experience is needed as the number of reported cases remains limited.     

Small cell carcinoma of the esophagus. Cytology and immunohistology in four cases.

Four cases of small cell carcinoma of the esophagus diagnosed by cytology, with subsequent histologic confirmation, were reviewed. The presence of small malignant cells in isolation with minimal cytoplasm was the common characteristic cytologic finding. Cellular molding was observed only focally in two cases, and streaking of nuclear material was not observed in any smear. The tumor cells were argyrophilic and not argentaffinic. Immunohistochemically the neoplastic cells were consistently immunoreactive with low-molecular-weight cytokeratins and epithelial membrane antigen. Esophageal washings as well as endoscopic biopsies yielded diagnostic material in all cases, but the histologic material was remarkable for crush artifacts that hindered the microscopic interpretation.     

Bronchial cytology in pleural mesothelioma. A report of 3 positive cases, including 1 diagnosed initially on bronchial brushings

OBJECTIVE: To evaluate retrospectively the value of bronchial aspiration cytology in patients with histologically proven pleural mesothelioma, reappraising positive smears in light of conventional microscopic features and, when feasible, immunocytochemical investigations. STUDY DESIGN: In 3 cases of mesothelioma with bronchial brushings positive for malignant cells, the cytologic features were correlated with the histologic findings. RESULTS: Salient microscopic features included scant to moderate cellularity arranged in micropapillary clusters, morular aggregates with scalloped borders and isolated malignant cells. Intercellular clear spaces or windows suggesting a brush border on cell membranes were also noted. In cases with available material, immunocytochemistry was positive for keratins, epithelial membrane antigen and calretinin and negative for carcinoembryonic antigen. All the cases were histologically confirmed epithelial mesotheliomas. CONCLUSION: In rare cases, pleural mesothelioma cells are shed within the airway lumina and can be detected in bronchoscopic cytology specimens. Cytologic features seem comparable to their analogues in pleural effusions. Although no single criterion appears diagnostic, their combined documentation could ensure correct interpretation, especially if supported by a limited immunocytochemical panel.     

Cytology of bronchial benign granular-cell tumor

The cytologic features of a case with multiple bronchial benign granular-cell tumors are reported and compared with those of previously reported cases. Characteristic tumor cells were found in the bronchoscopic brushing smears and in cell block sections (but not smears) prepared from the washing fluid. These findings were confirmed by the bronchial biopsy and histologic study of the resected tumors. A cytologic diagnosis of bronchial granular-cell tumor should not be difficult because the cytologic appearance of the tumor cells is characteristic; however, the possibility of a concomitant tumor, such as adenocarcinoma or small-cell carcinoma, should be considered and excluded.     

Preoperative brush and impression cytology in ocular surface squamous neoplasms

OBJECTIVE: Preoperative cytologic diagnoses of ocular surface squamous neoplasms were evaluated and compared with histologic diagnoses. STUDY DESIGN: Impression cytology (Millipore filter paper) and brush cytology were applied to 32 patients who had conjunctival neoplasms. Papanicolaou-stained cytologic preparations and hematoxylin and eosin-stained histologic sections were examined by light microscopy. RESULTS: The brush technique was used on 27 patients; impression cytology was applied in 5 cases. Cytologic and histologic diagnoses were concordant in 26 cases. Squamous cell carcinoma or carcinoma in situ was diagnosed in 18 and dysplasia in 4 cases. Squamous metaplasia and normal-appearing conjunctival epithelial cells were diagnosed cytologically in four cases; of those histologic diagnoses, one was pterygium and three, conjunctival nevus. Four cases revealed discrepancies between the cytologic and histologic preparations. There was one false positive result, and one case was subconjunctival invasion of basal cell carcinoma of the eyelid. CONCLUSION: Impression and brush cytology are fast, cost-effective, reliable and noninvasive diagnostic tools for ocular surface squamous neoplasms. However, the brush technique has several advantages over impression cytology.     

Clinical and cytologic features of papillary neoplasms of the breast

OBJECTIVE: To compare the cytologic features benign and malignant papillary breast lesions. STUDY DESIGN: We reviewed the clinical and cytologic features in 29 cases of intraductal papilloma and 26 cases of atypical papilloma or papillary carcinoma that had been diagnosed by histologic examination. The diameter of the mass was examined as a clinical feature. The cytologic features evaluated were as follows: bloody background, row of tall columnar cells, naked bipolar nuclei, hemosiderin-laden macrophages, myoepithelial cells, single scattered atypical cells, cellularity, nuclear atypia, nuclear grade, apocrine metaplasia, eosinophilic cytoplasmic granules, papillary clusters, small papillae, cell balls and large sheets. RESULTS: Of the features evaluated, the diameter of the mass, naked bipolar nuclei and cell balls differed significantly between benign and atypical or malignant papillary neoplasms. The average diameter of a benign papillary neoplasm was 1.8 cm, and that of an atypical or malignant papillary neoplasm was 2.2 cm (p = 0.042). Naked bipolar nuclei were found in 27 cases of benign papillary neoplasm (93.1%) versus 19 cases of atypical or malignant papillary neoplasm (73.1%) (p = 0.050). Cell balls were found in 14 (48.3%) and 21 (80.8%) cases, respectively (p = 0.012). All 6 cases in which cell balls were present and naked bipolar nuclei were absent proved to be atypical or malignant papillary neoplasms. Of 17 cases in which cell balls were absent and naked bipolar nuclei present, 13 (76.5%) were benign papillary neoplasms. CONCLUSION: Most cytologic features overlapped in benign and atypical or malignant papillary neoplasms. Although they were not pathognomonic, naked bipolar nuclei and cell balls were cytologic features that differed significantly between benign and atypical or malignant papillary neoplasms. When papillary neoplasms of the breast are suspected in a cytologic smear, the combination of clinical examination, mammography and cytologic features should be considered to make the correct diagnosis.     

Cytologic features of cribriform-morular variant of papillary carcinoma of the thyroid: a case report

BACKGROUND: While the histology of cribriform-morular variant of papillary thyroid carcinoma has been well documented, its appearance on cytologic smears has rarely been described given the rarity of this tumor. CASE: A 28-year-old woman had a neck lump for an unspecified duration for which she sought medical attention. She was previously well, and there was no significant family history of illness. Fine needle aspiration of the thyroid mass disclosed columnar cells with fine to granular chromatin and nucleargrooves associated with papillary fragments and acinar formation. Occasional groups of epithelial cells forming morules, previously unreported on cytology, were present. An excision specimen of the left thyroid nodule revealed morphologic features of cribriform-morular variant of papillary carcinoma of the thyroid. CONCLUSION: A diagnosis of cribriform-morular variant of papillary carcinoma of the thyroid could be established on fine needle aspiration cytology, prompting exclusion of familial adenomatous polyposis and distinguishing it from other, more aggressive variants of thyroid carcinoma, such as columnar cell carcinoma.     

Invasive cervical thymoma masquerading as a solitary thyroid nodule. Report of a case studied by fine needle aspiration

A 49-year-old woman underwent fine needle aspiration (FNA) biopsy of a presumed thyroid nodule. The initial cytopathologic interpretation suggested a chronic lymphocytic thyroiditis or a malignant lymphoma. The examination of frozen sections during surgery also suggested the presence of a lymphoma. However, histopathologic examination of permanent sections showed the lesion to be an invasive ectopic lymphocyte-predominant thymoma adjacent to the thyroid. Immunoperoxidase staining of FNA cell block sections and permanent sections showed positivity for keratin, proving the epithelial nature of the elongated and spindle-shaped tumor cells. This case high-lights the need to be aware of unusual lesions that may occur in the area of the thyroid; recognizing the potential diversity of "thyroid" masses that ultimately prove to be of nonthyroid origin should aid in making the correct cytologic differential diagnosis and interpretation of FNA samples obtained from such masses.     

Immunohistochemical study of lysozyme, alpha 1-anti-chymotrypsin, tissue polypeptide antigen, keratin and carcinoembryonic antigen in effusion sediments

The cellular sediments of 42 malignant and 16 benign effusions (58 cases) were studied using the immunoperoxidase technique. Serial sections of formalin-fixed, paraffin-embedded residual sediments of effusions, sent for routine cytologic examination, were studied by commercially available polyclonal antisera against lysozyme, alpha 1-anti-trypsin, alpha 1-anti-chymotrypsin, tissue polypeptide antigen (TPA), a wide-spectrum anti-keratin, carcinoembryonic antigen (CEA) and, in single cases, thyroglobulin and prostate-specific antigen. A final definite diagnosis from histologic study of biopsy or autopsy specimens was known in all cases. All carcinomas, the mesotheliomas and the reactive mesothelial cells showed a positive reaction for TPA and, partly, the wide-spectrum keratin. Lysozyme could be demonstrated in the cells of the one proven malignant fibrous histiocytoma; all malignant epithelial cells were negative. Alpha 1-anti-chymotrypsin and alpha 1-anti-trypsin showed similar reactions: they were often positive in carcinoma cells of the breast, the bronchial system and the pancreas, in contrast to a mostly negative reaction in carcinomas of the stomach and ovary. CEA showed considerable differences; it was always negative in benign and malignant mesothelial proliferations but mostly positive in carcinomas of the stomach, pancreas and bronchial system. It was only positive in less than 20% of the carcinomas of the breast and always negative in the proven malignant effusions of primary carcinomas of the ovary and prostate. Studying a combination of several tumor markers is possible in serial paraffin-embedded sections and may be a valuable criterion in the cytologic diagnosis of effusions.     

Fine needle aspiration cytology of high grade mucoepidermoid carcinoma of the breast: a case report

BACKGROUND: Primary mucoepidermoid carcinoma of the breast is a very unusual tumor. It is often misdiagnosed, masquerading under different diagnoses. The cytologic assessment is especially difficult when the lesion is high grade. One reported case was initially diagnosed by fine needle aspiration cytology. CASE: A 69-year-old woman presented with a 6 x 4-cm tumor located in the upper outer quadrant of the right breast. The first cytologic diagnosis suggested ductal carcinoma with atypical squamous metaplasia; further review disclosed that the clusters of epithelial ductal cells displayed a mixed pattern of glandular, squamous and intermediate cells. There also was a scant intracellular and extracellular mucous substance, confirming the diagnosis of mucoepidermoid carcinoma. Histochemistry and immunohistochemistry, performed on the tumor and lymph node metastases, showed cellular staining for periodic acid-Schiff, and keratin, epithelial membrane antigen and carcinoembryonic antigen demonstrated the epithelial origin. The high expression of Ki-67, as well as the finding of 24 metastasized nodes in the axilla, demonstrated the tumor's aggressiveness. CONCLUSION: Fine needle aspiration cytology is a very reliable tool in achieving a fast and accurate diagnosis of primary mucoepidermoid carcinoma of the breast.     

Epithelial myoepithelial carcinoma of the parotid gland with malignant ductal and myoepithelial components arising in a pleomorphic adenoma: a case report with cytologic, histologic and immunohistochemical correlation

BACKGROUND: To describe the cytologic, histologic and immunohistochemical findings of a case of epithelial myoepithelial carcinoma (EMC) arising from a pleomorphic adenoma (PA) of the parotid with both malignant epithelial and myoepithelial components. CASE: A 29-year-old female presented with a 1.5 x 1.5-cm, palpable mass of the left parotid of 7-8 months' duration with recent enlargement and pain. Fine needle aspiration biopsy (FNAB) revealed biphasic epithelial (small cell) and myoepithelial (large/clear cell) clusters arranged in a pseudopapillary and trabecular pattern with abundant hyaline material with many naked nuclei, together with areas typical of pleomorphic adenoma (PA) was noted. The cytology was reported as salivary gland neoplasm, "suggestive of adenoid cystic carcinoma, less likely pleomorphic adenoma." The mass was excised and histologically reported as "pleomorphic adenoma, with focal invasion of one resected margin." Four months later the tumor recurred, and FNAB showed almost the same cytologic features as did the previous aspirate. Due to early recurrence, previous histologic sections were reviewed, and typical areas of a biphasic pattern of EMC with atypicality and mitosis of both components was found. The final diagnosis was EMC ex PA. CONCLUSION: Although previous reports mention the difficulties in diagnosing EMC and differentiation from the more common salivary gland neoplasms such as PA, we like to emphasize the cytologic confusion that results when the tumors coexist.     

乳腺浸润性微乳头状癌临床病理及免疫组织化学分析

目的探讨乳腺浸润性微乳头状癌的临床病理特征、诊断与鉴别诊断要点。方法对乳腺浸润性微乳头状癌进行临床病理分析、组织形态学及免疫组化染色观察,结合文献对其临床表现、病理形态特点及鉴别诊断进行探讨。结果浸润性微乳头状癌光镜下特征性表现为癌巢由呈桑椹状或(和)腺管型的微乳头状癌巢组成,与网状间质间形成明显的空隙(主间质分离)。瘤细胞ER、PR、C-erbB-2、CD44V6阳性;Actin(sm)阴性;EMA在瘤细胞簇外周细胞膜和中间腔缘呈阳性表达。结论乳腺浸润性微乳头状癌可在病理诊断时作为一种单独的类型提出。     

Micropapillary variant of transitional cell carcinoma of the urinary bladder: a report of three cases with cytologic diagnosis in urine specimens

BACKGROUND: Micropapillary transitional cell carcinoma is a recently described, aggressive variant of bladder cancer. Its cytologic features in urine have not been previously characterized. CASES: Three cases illustrate the urinary cytologic features of this high grade urothelial carcinoma and its concurrent biopsy findings. This tumor is similar to low. grade urothelial lesions of the bladder, tends to present as micropapillary clusters in urine and yet has high grade nuclear features within these clusters that help with the differential diagnosis of a flat, high grade urothelial carcinoma. CONCLUSION: The micropapillary type of transitional cell carcinoma is a distinct morphologic entity with an aggressive clinical course. Recognizing its presence in urinary cytology, albeit a rare occurrence, is important in distinguishing this lesion from the more indolent, low grade papillary lesions and high grade urothelial carcinomas, which continuously shed single malignant urothelial cells.     

Robinson cytologic grading of invasive ductal breast carcinoma: correlation with histologic grading and regional lymph node metastasis

OBJECTIVE: To evaluate the importance of cytologic grading of breast carcinoma and its association with histologic grading and the existence of axillary lymph node metastasis. STUDY DESIGN: Aspirates and surgical samples from 100 patients with invasive ductal breast carcinoma not otherwise specified were studied. In 50 patients, > or = 1 metastatic nodes were identified. The cytologic grade was evaluated using the Robinson method and the histologic grade using the Elston modification of the Bloom-Richardson method. A study was undertaken to establish the association between histologic and cytologic grades and to compare the various parameters used to evaluate cytologic grade with the presence of axillary node metastasis. RESULTS: A statistically significant association was observed between cytologic and histologic grades (p < 0.0005) and between cytologic grade and presence of axillary metastasis (p < 0.0005). Similarly, cell dissociation (p < 0.0005), cell uniformity (p = 0.0010) and the appearance of nuclear margins (p < 0.0005) all displayed a positive correlation with regional metastasis. CONCLUSION: Cytologic grade may provide relevant information on the aggressiveness of invasive ductal breast carcinoma and could be a useful parameter to take into consideration when selecting neoadjuvant therapy.