Distinction between bronchioloalveolar carcinoma and hyperplastic pulmonary proliferations: A cytologic and morphometric analysis

The objectives of this study were to identify key cytologic features for the morphologic differentiation of bronchioloalveolar carcinoma from reactive pulmonary proliferations, and to determine if morphometry of the cytologic specimens could provide additional data to distinguish the two processes. We analyzed 15 morphologic criteria in pulmonary cytologic specimens from 17 histologically proven cases of bronchioloalveolar carcinoma and 13 cases with reactive cellular changes and compared the findings using univariate analysis. This revealed four statistically significant features more commonly associated with bronchioloalveolar carcinoma: (i) predominance of two- and three-dimensional tissue fragments, (ii) tenacious intercytoplasmic connections between cells, (iii) intranuclear cytoplasmic inclusions, and (iv) paucity of multinucleated cellular forms. Morphometric measurement revealed significant differences between the mean of the nuclear area of benign reactive cells and that of the malignant cells. The utilization of these criteria is helpful to diagnose bronchioloalveolar carcinoma and to distinguish it from reactive pulmonary processes. Diagn. Cytopathol. 16:396–401, 1997. © 1997 Wiley-Liss, Inc.     

Giant cell carcinoma of the lung impact of diagnosis and review of cytological features

Giant cell carcinoma of the lung is a specific type of lung carcinoma characteristically associated with a highly aggressive clinical behavior. This tumor comprises approximately 1-5% of all lung cancers, affecting a similar patient population as other primary pulmonary carcinomas. It is not routinely treated surgically, owing to the fact that it is metastatic at the time of diagnosis. The cytological diagnosis of this entity on aspiration biopsy has an appreciable impact on patient care. We retrospectively examined 15 cases of lung fine-needle aspirates in which a diagnosis of giant cell carcinoma or large cell carcinoma with giant cell features was made. We applied the criteria for cytological diagnosis of giant cell carcinoma previously set forth in the literature. In cases where there is a tissue diagnosis, we compared the results with the corresponding fine-needle aspirates and correlated them with patient survival. Conclusions are made regarding the reliability of the diagnostic criteria of this malignancy.     

Papillary adenocarcinoma of the lung is a more advanced adenocarcinoma than bronchioloalveolar carcinoma that is composed of two distinct histological subtypes

To clarify the clinicopathological nature of papillary adenocarcinoma (PA) of the lung, 20 cases of PA were collected consecutively from resected adenocarcinoma of the lung, studied immunohistochemically and, using molecular techniques, compared with bronchioloalveolar carcinoma (BAC). Clinicopathologically, PA occurred in 7.4% and dominantly in female patients. Morphologically, PA was divided into two subtypes according to the presence of residual alveolar structures, detected by elastica van Gieson stain. One of these subtypes was closely related to the morphology of BAC and might be diagnosed as adenocarcinoma with mixed subtypes. The other PA subtype was composed of tall columnar cells and grew compressively, which was similar to type F adenocarcinoma previously reported by Noguchi et al. Immunohistochemical studies using lung tissue-specific antigens, progression markers and tumor suppressor products found that PA seemed a more advanced adenocarcinoma than BAC, but no differences were observed among PA subtypes. Molecular biological analysis using three microsatellite markers at chromosome 3p revealed more frequent loss of heterozygosity in PA than BAC, with no differences among PA subtypes. These findings suggest that PA is a more advanced adenocarcinoma subtype than BAC. Further investigations are needed to clarify true PA as clinicopathologically and biologically independent from other histological subtypes of adenocarcinoma of the lung.     

Recurrence of bronchioloalveolar carcinoma in donor lung after lung transplantation: microsatellite analysis demonstrates a recipient origin

Bronchioloalveolar carcinoma is a distinctive subtype of pulmonary adenocarcinoma, without effective therapy, although there have recently been some attempts to use lung transplantation. However, a high post-transplantation local recurrence rate is described with some controversy regarding the possible involved mechanisms, the main possibilities being the lymphatic spread and aerosolization. Presented herein is a case of a bilateral lung transplantation for a bilateral and pneumonic form of non-mucinous bronchioloalveolar carcinoma in a 43-year-old woman. The histological analysis of mediastinal lymph nodes during surgery did not show neoplastic cells. Thirty-five months after transplantation several nodular opacities in donor lungs were detected. Three pulmonary wedge resections were performed showing a non-mucinous bronchioloalveolar carcinoma with the same histological characteristics as the primary. Again, the mediastinal lymph nodes were tumor free. A complete microsatellites molecular analysis was performed to compare the primary and recurrent carcinoma using capillary electrophoresis, showing that the recurrent tumor was generated in a recipient cellular clone. The absence of lymph node metastasis and the molecular evidence of the recipient origin of the neoplasm supports the contamination of the new lungs at the time of implantation as being the reason for the high incidence of recurrence after lung transplantation in this kind of disease.     

Detection of telomerase expression in fine-needle aspirations and fluids

The cytologic examination of fine-needle aspirates and fluid specimens is plagued by a persistent false negative rate. The rate of false negative results will be decreased if sensitive molecular assays can be developed to detect cytologically malignant cells. The current study investigated telomerase expression as a potential marker of malignancy, using the telomeric repeat amplification protocol (TRAP) in fine-needle aspirates and fluid specimens. TRAP was performed on 24 fine-needle aspirate and 24 fluid specimens from different body sites and of different histological diagnoses. We found that 6 of 12 fine-needle aspirate specimens that were cytologically positive for malignant cells expressed telomerase activity, while no specimens that were cytologically suspicious for malignancy, atypical, or negative tested positive for telomerase activity. Of the fluid specimens, 4 of 6 cytologically positive cases and 1 of 18 cytologically negative cases expressed telomerase. Seven of eight telomerase negative, cytologically positive specimens contained only rare malignant cells in a very bloody background. Peripheral blood contamination is a possible pitfall in the TRAP assay, as applied in the current study, because the assay is standardized to protein concentration that may be derived from lysed red blood cells. We conclude that with further technical refinement, the TRAP assay could become a useful adjunct in the cytologic examination of fine-needle aspirates and fluid samples. Diagn. Cytopathol. 1998;18:431–436. © 1998 Wiley-Liss, Inc.     

Poorly-differentiated adenoid cystic carcinoma: Cytologic appearance in fine-needle aspirates of distant metastases

Adenoid cystic carcinoma (ACC) is a primary salivary-gland neoplasm which typically yields characteristic cytomorphology upon fine-needle aspiration (FNA). We report on the FNA findings of a case of ACC metastatic to the liver which demonstrated a predominantly solid, poorly-differentiated pattern, an unusual but well-recognized subtype associated with a poor clinical outcome. The FNA findings in 7 additional cases of ACC metastatic to distant sites were also reviewed, with 4 cases displaying a prominent poorly-differentiated component. These findings suggest that, although not commonly recognized in salivary-gland FNAs, the poorly-differentiated pattern of ACC does occur in metastatic deposits and should be recognized as such, thereby preventing a needless search for a second primary malignancy. Diagn Cytopathol 1996;15: 296–300. © 1996 Wiley-Liss, Inc.     

Morphologic predictors of papillary carcinoma on fine-needle aspiration of thyroid with ThinPrep preparations

Although the cytologic features of papillary carcinoma of the thyroid are well-known, none is entirely specific. We conducted this study to determine the minimal criteria necessary to achieve 100% specificity for the diagnosis of papillary carcinoma on fine-needle aspiration (FNA). Forty patients with histologically confirmed papillary carcinoma and 17 patients with other thyroid lesions who underwent preoperative FNA at Beth Israel Deaconess Medical Center during a 4-yr period were included in the study. All cytology slides were prepared with the ThinPrep processing technique. Various architectural and nuclear features were evaluated, with a score assigned to each feature, and correlated with the histologic diagnosis of papillary carcinoma. Intranuclear inclusions, papillary and/or sheet arrangements, nuclear grooves, powdery chromatin, nuclear molding, high cellularity, and small nucleoli were significantly associated with papillary carcinoma (P < 0.05). The requirement of any intranuclear inclusions and many nuclear grooves, or a minimum of sum of scores (of the above eight features) of 10, yields 100% specificity and approximately 70% sensitivity. Cases with fewer features can be reported as suspicious or indeterminate for papillary carcinoma. A quantitative/probabilistic approach in the reporting of thyroid FNA provides a practical guide for management of patients with thyroid nodules.     

Cytologic diagnosis of salivary duct carcinoma: A review of seven cases

The cytomorphologic findings in fine-needle aspirates from 7 cases of salivary duct carcinoma (SDC) are reviewed and correlated with the histologic features. Malignant cytologic characteristics are clear in this tumor, and no false-negative results were obtained. But the absence of cribriform or papillary groups suggests an inconclusive diagnosis and sometimes the need to establish a differential diagnosis with other salivary tumors, and in particular with adenocarcinoma not otherwise specified (ADC-NOS) and high-grade mucoepidermoid carcinoma (h-g MEC). The pitfalls in the cytologic diagnosis of this tumor are discussed. In addition, the literature on the subject is reviewed. Diagn. Cytopathol. 1998;19:120–123. © 1998 Wiley-Liss, Inc.     

Metastatic bronchioloalveolar carcinoma presenting as a solitary thyroid nodule: report of a case with fine-needle aspiration cytopathology

Although cancers metastatic to the thyroid are frequently mentioned in autopsy studies, such a finding is quite rare in routine clinical practice. Metastatic non-small-cell carcinomas to the thyroid may present a diagnostic dilemma, particularly when they share morphological similarities with primary thyroid tumors. Herein, we report a case of metastatic bronchioloalveolar carcinoma that presented as an isolated left thyroid nodule in a 68-year-old woman. The aspirates were cellular and showed numerous papillary-like tissue fragments, elongated nuclei with prominent nuclear grooves, frequent mitoses, and psammoma bodies. The latter features raised the possibility of papillary thyroid carcinoma. However, also seen were three-dimensional tumor nests and acinar-forming fragments. Immunostains (positive for cytokeratin-7 and carcinoembryonic antigen and negative for cytokeratin-20 and thyroglobulin) confirmed the metastatic nature of the carcinoma. In a patient with known primary neoplasm, the differential diagnosis of a thyroid nodule should always include a metastatic lesion along with primary neoplasia.     

A case of matrix-producing metaplastic carcinoma of the breast exhibiting similarities to pleomorphic adenoma on fine-needle aspiration cytology

The distinction between matrix-producing metaplastic carcinoma (MPMC) and pleomorphic adenoma (PA) is sometimes unclear in breast pathology, especially on core needle biopsy. Herein, we presented a 66-year-old woman with MPMC of the breast that looked like PA on fine-needle aspiration cytology (FNAC). On FNAC, the appearance of abundant myxoid matrix along with cellular clusters composed of monotonous cellular populations looked like salivary PA, which we were familiar with owing to the frequency in routine pathological practice. Thus, the possibility of breast PA, the counterpart of salivary PA, was considered. However, the tumor location was different from where breast PA frequently occurs, i.e. the retroareolar region. Therefore, we eliminated the possibility of breast PA and avoided the erroneous cytological diagnosis. It is should be kept in mind that MPMC can look like PA on FNAC.     

Prognostic analysis of pulmonary adenocarcinoma subclassification with special consideration of papillary and bronchioloalveolar types

AIMS: The third edition of the World Health Organization (WHO) classification of lung tumours has been published and is expected to become the standard nomenclature. The aim of this study was to assess the usability and prognostic significance of the WHO classification in comparison with other recent classifications. METHODS AND RESULTS: One hundred and forty-seven resected pulmonary adenocarcinoma cases were reviewed and histologically classified according to the WHO classification (1999) and the classification by Noguchi (1995). Papillary carcinomas as described by Silver and Askin (1997) were also identified. Since the papillary type in the WHO classification is not strictly defined, we compared the following two kinds of WHO classification: (i) WHO-N; WHO classification adopting Noguchi Type F as the definition of the papillary type, namely, pure papillary adenocarcinoma without a bronchioloalveolar component; (ii) WHO-SA; WHO classification adopting papillary carcinoma by Silver and Askin as the definition of the papillary type, namely, tumour with papillary structure constituting at least 75% of the lesion. The bronchioloalveolar carcinoma of the WHO classification showed a better prognosis than other subtypes in both overall and Stage I disease limited survival analysis. In analysis limited to Stage III disease, only the papillary type of WHO-SA showed a significantly worse prognosis. CONCLUSIONS: WHO-SA is recommended for prognostic correlation.     

Basal cell carcinoma metastatic to the salivary glands: Differential diagnosis in fine-needle aspiration cytology

A disparate group of salivary gland neoplasms is characterized by small, uniform, hyperchromatic, basaloid cells. This “small blue cell” pattern is most common in non-Warthin's types of monomorphic adenoma, or in adenoid cystic carcinoma. Small cell anaplastic carcinoma (primary or metastatic), metastatic basaloid squamous cell carcinoma, basal cell adenocarcinoma, and metastatic nasopharyngeal carcinoma are rarely encountered but may present a cytologically similar appearance. We report one female and two male patients (median age = 84 yr) with cutaneous-type basal cell carcinoma (BCC) aspirated from metastatic deposits in the parotid (2 cases) or the submandibular (1 case) gland. One was correctly classified at the time of aspiration, based on a previous history of multiple facial BCC. One was interpreted as carcinoma, the previous history being unavailable at the time of FNA. Smears in these two cases show necrosis and rare keratotic cells. The third case was mistaken for pleomorphic adenoma (PA); the smears showed metachromatic fragments of collagenous tumor stroma that were misinterpreted as the matrix material typical of PA. Similar material was identified in the other two cases. When the “small blue cell” pattern is encountered in salivary gland cytology, one should consider BCC, especially if necrosis is identified. The desmoplastic tumor stroma of BCC may mimic the chondroid matrix of PA. Careful consideration of previous history is very important. Diagn. Cytopathol. 16:247–252, 1997. © 1997 Wiley-Liss, Inc.     

Fine-needle aspiration cytology of a minimal carcinoma of the breast with neuroendocrine features

A case of breast carcinoma with neuroendocrine features is described in a 62-year-old nulliparous female, in which the fine-needle aspiration cytodiagnosis was of a breast carcinoma. Carcinoma of the breast with neuroendocrine features is an unusual variant which may be observed in several histologic types of mammary carcinoma. An awareness of this tumor is essential in view of the increasing use of fine-needle aspiration cytology as a minimally invasive, first line of investigation of a breast abnormality. The case presented here is also of interest since the tumor was only 5 mm in diameter (a minimal carcinoma). Diagn. Cytopathol. 1998;19:107–109. © 1998 Wiley-Liss, Inc.     

Bronchioloalveolar carcinoma: Diagnostic pitfalls and immunocytochemical contribution

Because bronchioloalveolar carcinoma (BAC) commonly displays bland cytologic appearance, there is a good potential for misinterpretation. The aim of this study was twofold: one was to identify the most reproducible cytomorphologic features to distinguish BAC from conventional lung adenocarcinoma (CLA) on fine-needle aspiration (FNA), and the other was to investigate the staining characteristics of these two variants of lung carcinoma with P53 tumor suppressor gene immunostain and their potential value in the distinction between the two entities. Cytology records of 13 histologically documented BACs was retrieved: 7 FNA, 3 bronchial washing/ bronchial brushing (BW/BB), and 3 scraping smears of surgical specimens. Two cases had both FNA and BW/BB material. Immunostains for P53 protein, carcinoembryonic antigen (CEA), and Ki67(MIB-1) monoclonal antibodies were performed on 13 BACs (FNA cell blocks and tissue) and on 11 FNA cell blocks of CLA. Cytologically, BAC showed uniform cells with abundant, lacy cytoplasm, and bland, folded nuclei arranged singly, in papillary clusters, and sheets. Immunocytochemically, one BAC and one CLA were technically unacceptable. Of the 12 remaining BAC cases, 10 were reactive with CEA, 9 reactive with Ki67 (>5%), and 4 reactive with P53. Of the 10 remaining CLAs, 9 were positive with CEA, 9 were reactive with Ki67 (>5%), and 8 were reactive with P53. We conclude that BAC demonstrates distinctive cytologic features, but difficulty may be encountered with well-differentiated CLA, metastatic adenocarcinoma, and other lesions. Immunocytochemically, CEA and Ki67do not appear to be discriminate, but P53 may be of value in distinguishing BAC from CLA. Attention to subtle nuclear changes, characteristic grouping, cellular arrangement, and P53 reactivity could enable cytopathologists to accurately diagnose BAC. Diagn. Cytopathol. 1998;18:301–306. © 1998 Wiley-Liss, Inc.     

Cytologic features in fine-needle aspirates from a sclerosing mucoepidermoid thyroid carcinoma with eosinophilia

Fine-needle aspirates from a sclerosing mucoepidermoid thyroid carcinoma with eosinophilia showed peculiar but nonspecific features. The overall picture seems more important than individual elements in recognizing this rare entity cytologically, since the predominant type of malignant cells has a deceptively bland appearance. The differential diagnoses include other primary thyroid malignancies, as well as metastatic growth and Hashimoto's thyroiditis. Diagn Cytopathol 1996;15:301–305. © 1996 Wiley-Liss, Inc.     

Salivary duct carcinoma ex pleomorphic adenoma: Analysis of the findings in fine-needle aspiration cytology and histology

Salivary duct carcinoma (SDC) is an uncommon and highly aggressive neoplasm that reveals histopathologic features resembling infiltrating duct carcinoma of the breast and prostate. SDC arising on the basis of preexisting pleomorphic adenoma (PA) is very rare. This report describes the fine-needle aspiration (FNA) cytology of a case of SDC ex PA. FNA smears were cellular with cells with large, pleomorphic nuclei, some prominent nucleoli, and finely vacuolated cytoplasm. The neoplastic cells were forming groups, sheets, and papillary structures and a cribriform pattern was present in some sheets. Mitotic figures were frequently seen. Necrosis was prominent in the background. Histologic sections of the tumor revealed areas of comedo carcinoma, papillary carcinoma, and infiltrative carcinoma as well as multiple foci of PA. The presence of a cribriform pattern, tumor cells resembling breast ductal carcinoma cells, and a necrotic background are helpful features for an accurate cytodiagnosis of SDC. Diagn. Cytopathol. 1998;19:201–204. © 1998 Wiley-Liss, Inc.     

Concomitant lymphoma and metastatic carcinoma in a lymph node: Diagnosis by fine-needle aspiration biopsy in two cases

Concomitant lymphoma and metastatic carcinoma are an unusual occurrence in a lymph node. We report two patients in whom synchronous malignancies were diagnosed by fine-needle aspiration biopsy (FNAB). In one case, the FNAB diagnoses of both small lymphocytic lymphoma and metastatic breast carcinoma were the initial diagnoses. In the second case, metastatic poorly differentiated squamous carcinoma was an unexpected finding in a patient with a history of small lymphocytic lymphoma. The aspirates in both cases showed two distinct cell populations, one consisting of a dispersed population of small uniform lymphoid cells and the other comprising large atypical single cells and cohesive clusters of epithelial cells. In both cases, the cytologic diagnoses were supported by immunohistochemical and flow cytometric studies. Diagn. Cytopathol. 1997;17:287–291, 1997. © 1997 Wiley-Liss, Inc.     

Diagnostic clues for differentiating Merkel cell carcinoma from lymphoma in fine-needle aspiration cytology

Nodal fine needle aspiration (FNA) is usually the first procedure in the work-up of malignancy of unknown primary. Merkel cell carcinoma (MCC) is an aggressive cutaneous cancer more common in Caucasians but rare among Asians. It is a diagnostic challenge in evaluating FNA from a metastatic MCC without the knowledge of a current or prior history of skin cancer. We report the case of a Taiwanese male with cervical and axillary masses. The diagnosis of the FNA from the axillary lymph node was lymphoproliferative lesion suspicious for lymphoma. The histopathological evaluation of nodal biopsy revealed a metastatic neuroendocrine carcinoma and the subsequent excision of the right palm tumor confirmed MCC. Retrospective review of the FNA and imprint cytology smears of the nodal biopsy showed nuclear molding, Indian filing and rare cytoplasmic pale bodies, but no lymphoglandular bodies. Cytologically metastatic MCC may mimic small round cell tumor including lymphoma, we consider these three cytological features as additional diagnostic clues for metastatic MCC. In this report, we present the cytologic and pathological features of this metastatic MCC and discuss the differential diagnosis of the cytologic mimickers.