Cytology and immunocytochemistry of bronchioloalveolar carcinoma

A study of the value of cytologic examination in the diagnosis of bronchioloalveolar carcinoma showed that fine needle aspiration (FNA) cytology is a definitive means of making the diagnosis of bronchioloalveolar carcinoma. In experienced hands, FNA cytology approached a diagnostic accuracy of 100%. With exfoliative cytology, technically adequate sputum samples offered an 82% diagnostic yield; sputum cytology should thus be considered as an adjunct method in establishing the diagnosis. Several cytologic features that strongly suggest the diagnosis of bronchioloalveolar carcinoma and help to differentiate it from adenocarcinomas of other body sites are outlined. It is also concluded that immunocytochemical stains have limited value in differentiating bronchioloalveolar carcinoma and other types of clear cell malignant neoplasms, including mesothelioma, unless a panel of antibodies is used, and are of no value in ascertaining whether the cells are benign or malignant.     

Primary papillary serous carcinoma of the peritoneum: report of a case with diagnosis by fine needle aspiration and immunocytochemistry

BACKGROUND: Primary papillary serous carcinoma (PPSC) of the peritoneum is a rare neoplasm, histologically indistinguishable from papillary serous carcinoma of the ovary, which diffusely involves the peritoneum but spares or minimally invades the ovaries. To the best of our knowledge, the preoperative and the fine needle aspiration diagnosis of this disorder have not been reported before. CASE: A woman developed an extensive peritoneal neoplasm 4 years after hysterectomy and bilateral salpingo-oophorectomy for benign disease. Fine needle aspiration of the tumor was performed, and the cytologic and immunocytochemical findings were consistent with papillary serous carcinoma. A diagnosis of PPSC of the peritoneum was rendered because review of all slides from previous surgical specimens showed no evidence of carcinoma and no other primary tumors were found elsewhere. CONCLUSION: Fine needle aspiration cytology coupled with immunocytochemical and clinical data allows an unequivocal preoperative diagnosis of papillary serous carcinoma (primary peritoneal or with an ovarian origin). The sole limitation to establish a primary peritoneal origin before surgery is the requirement to histologically study the ovaries. Based on this fact, the preoperative fine needle aspiration cytology diagnosis of PSCP should be restricted to oophorectomized patients.     

Intranuclear inclusions in fine needle aspirates of bronchial low grade mucoepidermoid carcinoma with clear cell change: a report of two cases

BACKGROUND: Mucoepidermoid carcinoma of the bronchus is a rare neoplasm that can be recognized on histology as well as cytology by the presence of three characteristic cell types: mucus secreting, epidermoid and intermediate. We encountered two cases displaying unusual cytologic features, including clear intranuclear inclusions. CASES: Two females, aged 33 and 39, presented with an intrabronchial tumor and pulmonary parenchymatous mass, respectively. Fine needle aspiration of both tumors showed similar cytologic features, with a dominant population of cells with bland nuclei and wide cytoplasm, and frequent intranuclear inclusions. A minor component of mucus-secreting cells was also recognized. Histologically, both tumors corresponded to the clear cell variant of mucoepidermoid carcinoma. CONCLUSION: The cytologic picture in our cases has not been described previously in fine needle aspirates of mucoepidermoid carcinoma, in neither the bronchus nor salivary gland. The differential diagnosis of a monotonous population of epithelial cells with intranuclear inclusions involves bronchioloalveolar carcinoma, but the absence of the characteristic sheet pattern, as well as the clinical and image findings, excludes this possibility. The lack of atypia and intrabronchial location limits the scope to carcinoid and salivary gland-type tumors of the bronchus. Since we were aware of the possibility of unusual cytologic presentations of mucoepidermoid carcinomas, search for different cellular populations suggested the precise diagnosis.     

Coexistence of aspergillosis and squamous-cell carcinoma in the maxillary sinus proven by preoperative cytology

The case of a 56-year-old female with coexisting aspergillosis and squamous-cell carcinoma in the maxillary sinus is reported. The diagnosis was established by cytologic study of washings of the sinus before and after admission and was confirmed by exploratory antrotomy. To our knowledge, this is the first case in which the coexistence of fungus and neoplasm in the paranasal sinus was established by preoperative cytologic diagnosis.     

Morphologic and immunocytochemical studies of bronchioloalveolar carcinoma at Duke University Medical Center, 1968-1986

Between 1968 and 1986, the tumor registries at Duke University Medical Center and Durham VA Medical Center accumulated a total of 193 patients with a diagnosis of bronchioloalveolar carcinoma (BAC). All available histologic sections of primary lung tumors and all available respiratory and pleural cytologic material were reviewed for 135 cases having an initial histologic diagnosis of BAC and no history of a primary nonpulmonary adenocarcinoma. Thirty-nine cases showed a pure BAC pattern in histologic sections; 76 showed a dominant BAC pattern with focal areas of fibrosis and acinar differentiation; 16 were carcinomas with a focal BAC pattern; and 4 were adenocarcinomas lacking a BAC pattern. Of the 115 cases with at least a dominant BAC pattern, 51 showed predominantly mucinous differentiation while 64 showed predominantly nonmucinous differentiation. Adequate cytologic material was available for review from 111 patients. For cases having at least a dominant BAC pattern, tumor cells were present in 77 of 172 adequate sputums (44.8%), 36 of 133 bronchoscopy specimens (27.1%), 15 of 18 needle aspirates (83.3%) and 14 of 15 pleural fluids (93.3%). Of all patients in this group, 60.2% had at least one specimen positive for malignancy. No cytologic features clearly distinguished adenocarcinomas having only focal bronchioloalveolar differentiation from those with a pure or dominant BAC pattern. A significant degree of overlap was observed in the cytologic features of mucinous and nonmucinous tumors. Histologic sections from 19 mucinous and 16 nonmucinous tumors were stained with monoclonal antibody B72.3: all showed some staining, with no significant difference in degree of staining between the two groups. This suggests that expression of the tumor-associated glycoprotein TAG-72 is independent of mucinous differentiation.     

Histologic and cytologic patterns of lung cancer in 2,580 men and women over a 15-year period

This paper describes the relative frequencies and changes in the morphologic patterns of lung cancer, as documented in the histologic and cytologic specimens from 2,580 patients diagnosed and treated at Duke University Medical Center over a period of 15 consecutive years. During the first five years, the relative frequencies of the various types of lung cancers were, in descending order, squamous cell carcinoma (43.1%), large cell undifferentiated carcinoma (22.5%), adenocarcinoma of the acinar type (18.6%), small cell undifferentiated carcinoma (11.6%), bronchioloalveolar carcinoma (3.5%) and adenosquamous carcinoma (0.7%). During the second and third five-year periods, squamous cell carcinoma remained the most common neoplasm, but declined to 35.7%, while adenocarcinoma of the acinar type became the second most common lung cancer at 22.0%. The absolute and relative incidences of lung cancer in women showed a striking increase from 21.8% to 29.9%. During this same period, adenocarcinoma of the acinar type replaced squamous cell carcinoma as the most common primary lung cancer in women.     

Fine needle aspiration cytology diagnosis of renal medullary carcinoma: a case report

BACKGROUND: Renal medullary carcinoma is a recently described, highly aggressive neoplasm that affects predominantly young African American males with a history of sickle cell trait. To the best of our knowledge, this is the first report of fine needle aspirate cytology (FNAC) findings of renal medullary carcinoma. CASE: A 14-year-old, African American male with a history of sickle cell trait presented with the sudden onset of third cranial nerve palsy. Radiographic examination demonstrated possible tumor masses in the brain, thorax and left kidney. Ultrasound-guided fine needle aspiration was performed on the left kidney, and a cytologic diagnosis of "suspect renal medullary carcinoma" was rendered. The cytologic diagnosis was confirmed by tissue examination. CONCLUSION: The cytologic features of renal medullary carcinoma include loosely cohesive clusters and single epithelioid cells with cytologic atypia, including high nuclear/cytoplasmic ratios, hyperchromasia, prominent nucleoli and cytoplasmic vacuolation. These cytologic findings, coupled with clinical findings (young black male with sickle cell trait), allow recognition of this rare renal neoplasm.     

The diagnostic reliability of cytologic typing in primary lung cancer with a review of the literature

To evaluate the growing tendency in recent years to attribute more diagnostic reliability to cytologic methods, we investigated the accuracy of cytologic typing in specimens obtained from bronchopulmonary material by five different clinical sampling methods, comparing the cytologic diagnoses with the known histologic diagnoses. The study consisted of 232 cytologic specimens from 157 cases of primary lung cancer. Of the 232 specimens, 173 (75%) were correctly typed and 59 (25%) incorrectly typed with respect to the appropriate histologic diagnoses. When all sampling methods were considered together, the study demonstrated that well-differentiated epidermoid carcinoma and "oat cell" and spindle-polygonal anaplastic carcinomas yielded high cytologic typing accuracies. In poorly differentiated tumors, bronchioloalveolar cell carcinoma and bronchogenic adenocarcinoma, the correct cytologic typing was much lower. The different tumor types and their degrees of differentiation seem to be the decisive factors in cytologic typing accuracy. The findings of this study were compared with those of others and were found to be consistent with the results of even larger series of cases. For some types the typing accuracy was higher than that reported in other series, whereas for other types, e.g., adenocarcinomas, it was lower.     

Transitional cell carcinoma of the renal pelvis metastatic to the metacarpal. A case report correlating cytologic and histologic findings.

This report describes the cytologic, radiologic and histologic findings in a 76-year-old male who presented with a pathologic fracture of the first metacarpal bone as the result of metastatic transitional cell carcinoma. The primary neoplasm was sited in the right renal pelvis. Metastases were also detected in the liver and confirmed cytologically. Problems encountered with the cytologic diagnosis are explained by correlation with the histologic findings. The case also illustrates the importance of clinicopathologic correlation when interpreting fine needle aspiration biopsies.     

Cytology of metastatic neuroendocrine (Merkel-cell) carcinoma in pleural fluid. A case report

A case of Merkel-cell (neuroendocrine) carcinoma of the skin with extensive metastases, including pleural effusion, occurring over 20 years after primary resection and treatment, is reported. The histologic appearance of the primary neoplasm was identical to that seen in the biopsy specimens of the metastatic carcinoma involving the great toe and inguinal lymph nodes and to that of the residual neoplasm tissue found at necropsy. Electron microscopic examination of a lymph node metastasis demonstrated cytoplasmic microfilaments and numerous dense-core, peripheral, neurosecretory granules, as previously described in Merkel-cell carcinoma. Cytologic examination of a pleural fluid specimen demonstrated numerous small malignant cells closely resembling the cells seen in the histopathologic sections from the surgical and necropsy tissues involved by metastatic carcinoma. This is the first report of the cytologic findings in a patient with Merkel-cell carcinoma metastatic to the pleural cavity.     

Pulmonary fine needle aspiration cytopathology. A five-year correlation study

Transthoracic fine needle aspiration specimens with abnormal cytology were obtained from 272 patients between 1976 and 1980 at the University of Rochester Medical Center. A comparison was made between the original specific cytologic and final histologic diagnoses on 116 patients; an additional 16 patients with the cytologic diagnosis of small-cell carcinoma were evaluated by clinical criteria. Analysis of the data indicated that malignant neoplasms were identified correctly with an accuracy of 99%. There was a single false-positive diagnosis. Predictive values for a specific morphologic variant of pulmonary neoplasm were 70% for squamous-cell carcinoma, 86% for adenocarcinoma and 95% for small-cell carcinoma. The probable bases for diagnostic error are discussed. Confidence intervals calculated from these data compared favorably with those in recently reported studies. The results reconfirmed the value of fine needle aspiration cytopathology for the diagnosis of pulmonary neoplasms.     

Carcinoembryonic antigen content in fine needle aspirates of the lung. A diagnostic adjunct to cytology.

Carcinoembryonic Antigen (CEA) was measured in 59 consecutive fine needle aspirates (FNAs) of the lung from 58 patients to determine if the CEA content would enhance the sensitivity of the cytologic diagnosis. Twenty-eight males and 30 females with tumors 1-40 cm in diameter were studied. Final diagnoses were correlated with the clinical history, radiologic studies, tissue (when available) and follow-up. Image-guided FNAs were performed by radiologists using a 22-gauge Chiba needle and 20-mL syringe with one to four passes per specimen. Cytologic examination included rapid assessment in the radiology suite and a final diagnosis in 24 hours. CEA was measured by enzyme immunoassay using monoclonal antibody. Nine benign aspirates and 50 malignant aspirates were diagnosed. The sensitivity of cytology was 86% and specificity, 100%. Using 5 ng/mL as the cutoff, the sensitivity of CEA for malignant aspirates was 50% and specificity, 90%. The combined sensitivity of CEA and cytology was 95%. The mean CEA in malignant aspirates was 131 ng/mL and in benign aspirates, 2.41. The highest mean CEA was seen in adenocarcinoma, 402.6 ng/mL. Lower CEA content was seen in epidermoid carcinoma (58.6 ng/mL), large cell carcinoma (8.09), oat cell carcinoma, metastatic carcinoma of the kidney and breast, thymoma and lymphoma (each less than 1 ng/mL). Elevated CEA alone was diagnostic in two aspirates of bronchioloalveolar carcinoma; carcinoma with an unknown primary source, three; and large cell carcinoma, one. The adjunctive use of CEA in FNAs of the lung enhances the sensitivity of the cytologic diagnosis.     

Fine needle aspiration cytologic findings in metastatic basaloid squamous cell carcinoma of the head and neck.

Basaloid squamous cell carcinoma of the head and neck is a variant of squamous carcinoma the cytomorphology of which has not been examined previously. The cytologic features of metastatic basaloid squamous cell carcinoma in fine needle aspiration specimens from nine patients are described. The primary tumors, when known, were located in the base of the tongue, tonsil, epiglottis, nasopharynx, hypopharynx and false vocal cord. Each neoplasm had large fragments or clusters of crowded cells and scattered single cells in the cytologic smears. The cells had round or oval, hyperchromatic nuclei that often had single, small nucleoli. The nuclei usually were small or medium sized, but six tumors had a few cells the nuclei of which were large and pleomorphic. The cytoplasm was typically scant, and only three cases had occasional keratinized cells. Necrosis was present in six neoplasms. Three neoplasms, originally diagnosed as small cell undifferentiated carcinoma, contained numerous single cells and small clusters of cells with nuclear molding. On review, however, smears from these neoplasms also contained a few large fragments of tightly cohesive cells with larger, vesicular nuclei. Another basaloid squamous cell carcinoma had been interpreted elsewhere as an adenoid cystic carcinoma because of the presence of pseudoglandular structures with stromal cores. Although the cytologic features of basaloid squamous cell carcinoma may mimic those of other poorly differentiated carcinomas in fine needle aspiration specimens, they are sufficiently distinctive that a diagnosis of this variant of squamous cell carcinoma can be suggested for a patient whose primary neoplasm is located in the upper aerodigestive tract.     

Fine needle aspiration of primary pleomorphic liposarcoma of the breast. A case report

BACKGROUND: Primary liposarcoma of the breast is an extremely rare lesion. Only two cases describing the aspiration biopsy findings have been reported in the literature. We report the cytologic findings in an additional case, stressing the cytologic clues necessary to distinguish this neoplasm from a primary adenocarcinoma. CASE: A 53-year-old female presented to the emergency room with bleeding from a 20-cm, ulcerating mass in the right breast. Four months earlier she had been seen at another institution, where a diagnosis of poorly differentiated carcinoma was made by aspiration biopsy. Computed tomography had been negative for metastatic disease, and the patient refused further evaluation. Aspiration biopsy of the breast mass was repeated at our institution and interpreted as consistent with a poorly differentiated carcinoma. Histologic, immunophenotypic and ultrastructural evaluation of the mastectomy specimen revealed a pleomorphic liposarcoma. CONCLUSION: With increasing utilization of fine needle aspiration to evaluate breast lesions, it can be anticipated that unusual entities, including liposarcomas, will be encountered increasingly in breast aspirates. Therefore, it is important to consider liposarcoma in the differential diagnosis of aspirates showing isolated spindle and polygonal cells with vacuolated cytoplasm, nuclear scalloping and pleomorphism to avoid a misdiagnosis of carcinoma.     

Cytologic diagnosis of mesonephric adenocarcinoma of the urinary bladder

Mesonephric adenocarcinoma is a rare primary neoplasm of the urinary bladder, composed of papillary and glandular structures with clear-cell features. A case is reported in which cytologic examination of urine specimens showed the distinctive dimorphic cell population of small cells in papillary formations and larger cells with features of a clear-cell adenocarcinoma, permitting a specific diagnosis.     

Macrofollicular encapsulated variant of papillary thyroid carcinoma as a potential pitfall in histologic and cytologic diagnosis. A report of three cases

BACKGROUND: Macrofollicular encapsulated papillary carcinoma (MEPC) is a variant of papillary carcinoma with a favorable clinical course. Its characteristic histologic pattern could be mistaken for that of an adenoma or hyperplastic nodule. Fine needle aspiration of this neoplasm may not show the particular nuclear features of papillary carcinoma, so the cytologic diagnosis may be benign. CASE REPORTS: Three paradigmatic cases of MEPC with different histologic patterns, diagnosed as a follicular neoplasm using fine needle aspiration biopsy (FNAB) are described. Preoperative cytology showed scattered clusters of thyrocytes with prominent nuclear pleomorphism and irregularities and focal oxyphilic changes mixed with colloid and aggregates of typical thyrocytes. The histologic picture exhibits small, neoplastic foci showing a microfollicular structure within an encapsulated neoplasm with a macrofollicular pattern. In microfollicular areas obvious nuclear pseudoinclusions were seldom observed. CONCLUSION: MEPC represents a challenging tumor subtype that infrequently shows the pathognomonic cytologic characteristics of papillary carcinoma, and therefore it is much more difficult to diagnose with a FNAB. Nuclear pleomorphism and irregularity of the nuclear membrane of thyrocytes are clues to this variant, although in some cases a clear-cut preoperative diagnosis cannot be made.     

Preoperative aspiration cytology of breast tumors

During a ten-year period, 1,942 aspirations of 1,906 mammary tumors in 1,874 patients were performed before excisional biopsy or mastectomy. The cytology findings were categorized as positive (1,107 cases), suspicious (152 cases), atypical (183 cases), benign (166 cases) and unsatisfactory (298 cases). All cytologically positive cases with follow-up were confirmed histologically or by clinical observation. Follow-up showed that 96% of the cases in the suspicious category, 86% of the cases in the atypical category, 51% of the cases in the benign category and 72% of the cases in the unsatisfactory category had malignant neoplasms. Aspiration cytology diagnosed 1,031 of 1,539 primary malignant mammary neoplasms (67%) and 19 of 28 neoplasms (68%) metastatic to the breast; if unsatisfactory cases are excluded, these figures become 1,031 of 1,365 cases (75%) and 19 of 25 (76%), respectively. If those cases reported as suspicious are included with the positive cases and those reported as atypical are included with the negative cases, aspiration cytology would have a sensitivity of 84% for the presence of carcinoma, a specificity of 97% for the absence of carcinoma, a predictive value of 99% for a positive diagnosis and a predictive value of 56% for a negative diagnosis; the diagnostic efficiency would be 86%. Our findings reaffirmed that the cytologic diagnosis of mammary carcinomas is reliable but that negative or inconclusive cytologic findings should not be regarded as a definitive diagnosis if there is clinical suspicion of a malignant neoplasm.     

Signet-ring-cell (colloid) carcinoma of the urinary bladder. Cytologic, histologic and ultrastructural findings in one case

A 65-year-old female presented with a one-and-a-half-year history of intermittent, painless, gross hematuria. She was found to have a large bladder neoplasm. A cytologic diagnosis of signet-ring-cell (colloid) carcinoma was made on a bladder washing and was confirmed histologically by a cystoscopic biopsy. Subsequently, a radical cystectomy was performed. The cytologic findings of this rare pure signet-ring-cell carcinoma of the bladder, not previously described, are presented along with the histologic and ultrastructural findings.     

Polyclonal carcinoembryonic antigen staining in the cytologic differential diagnosis of primary and metastatic hepatic malignancies.

In order to assess the utility of immunocytochemical staining of bile canaliculi with a polyclonal antiserum to carcinoembryonic antigen (pCEA) in the differentiation of primary hepatocellular carcinomas from metastatic malignancies, pCEA staining was performed on fine needle aspiration specimens from hepatic lesions in 60 patients. The original cytologic diagnoses were hepatocellular carcinoma in 22 patients, metastatic neoplasm or cholangiocarcinoma in 27 patients and benign hepatocytes in 11 cases. The cytologic diagnoses of malignancy were confirmed by surgical excision, autopsy or clinical investigations in 82% of the patients. Follow-up data, supported by pCEA staining, reversed the original cytologic diagnosis in three cases. Bile canalicular pCEA staining was identified in 18 of 22 cases of hepatocellular carcinoma and in all 11 benign hepatocellular aspirates. All 27 cases of metastatic malignancy or cholangiocarcinoma were negative for canalicular pCEA staining, although 11 cases exhibited cytoplasmic staining. Interpretation of pCEA staining was not affected by the intermingling of malignant cells and benign hepatocytes. Predictive values were 100% for a positive test and 87% for a negative test. These findings indicate that staining with pCEA antiserum is a useful adjunct in the differential cytologic diagnosis of malignant hepatic lesions.     

Aspiration biopsy cytology of benign clear cell ("sugar") tumor of the lung

Benign clear cell tumor (BCCT) of the lung is an uncommon neoplasm, with about 24 cases reported in the literature. A fine needle aspirate from a histologically and ultrastructurally confirmed BCCT of the lung contained large irregular clusters of polygonal and spindle-shaped benign-appearing cells with vacuolated, granular, periodic-acid-Schiff-positive cytoplasm. Cytologic study of the aspirate suggested a pseudoinflammatory tumor; however, a metastatic renal cell tumor or a primary clear cell or mesenchymal tumor could not be excluded. The histologic, ultrastructural and cytochemical findings are also presented, and the cytologic differential diagnosis of this neoplasm is briefly discussed.