Andrea Abati

Adult T-cell leukemia/lymphoma: A cytopathologic, immunocytochemical, and flow cytometric study

Adult T‐cell leukemia/lymphoma (ATLL) is a postthymic lymphoproliferative neoplasm of T cells caused by human T‐cell lymphotropic virus (HTLV‐1). Most cases are found in Japan, the Caribbean basin, and West Africa.

Immunocytochemistry in effusion cytology: a contemporary review

Cytology plays a pivotal role in the diagnosis of pleural effusions. In many cases, immunocytochemistry (ICC) is required to elucidate the etiology of the atypical cells. Effusions are samples that present unique problems for ICC. To date there is no standardization of ICC methods for effusions and cytology in general.

E-cadherin, N-cadherin, and calretinin in pleural effusions: the good, the bad, the worthless.

The distinction between reactive mesothelial cells (RMC), malignant mesothelioma (MM), and metastatic adenocarcinoma (ACA) in pleural effusions may be impossible based on morphology alone. E‐cadherin, N‐cadherin, and calretinin are newly described immunocytochemical markers which can potentially be utilized for facilitating this distinction. E‐cadherin and N‐cadherin are calcium‐dependent intercellular adhesion molecules expressed in epithelial cells and mesenchymal/mesothelial cells, respectively. The differential expression of E‐cadherins in epithelial cells and N‐cadherins in mesothelial cells has been utilized to differentiate reactive mesothelial cells, MMs and ACAs. Calretinin is a calcium‐binding protein within the family of EF‐hand proteins. It is abundantly expressed in peripheral and central nervous tissues, and has been shown to consistently immunoreact with mesothelial cells. We studied cell block sections from 77 pleural effusions (22 RMC, 26 MM, and 29 ACA) to investigate the potential immunocytochemical use of anti‐E‐cadherin, anti‐N‐cadherin, and anti‐calretinin antibodies for differentiating between RMC, MM, and ACA in pleural effusions. A modified avidin‐biotin peroxidase complex (ABC) method was used. E‐cadherin immunostaining was observed in 14% of RMC, 46% of MMs, and 97% of ACAs. A distinct membrane staining pattern was seen in ACAs. The pattern of staining was cytoplasmic in all reactive RMC and varied from membrane to cytoplasmic in MMs. Anti‐N‐cadherin immunoreacted with 77% of RMC, 35% of MMs, and 48% of ACAs. Twenty‐seven percent of RMC, 58% of MMs, and 31% of ACAs immunoreacted with anti‐calretinin. Based on these results, we conclude that anti‐E‐cadherin is a potentially useful marker in the distinction of ACA cells from RMC. However, it is not as useful for the distinction of ACA and MM. Anti‐N‐cadherin and anti‐calretinin did not reliably distinguish between reactive mesothelial, MM, and ACA cells in pleural effusions. Diagn. Cytopathol. 1999:20:125–130. Published 1999 Wiley‐Liss, Inc.

Utility of the antibodies CA 19-9, HBME-1, and thrombomodulin in the diagnosis of malignant mesothelioma and adenocarcinoma in cytology

The distinction between malignant mesothelioma (MM) and adenocarcinoma (ACA) in cytologic specimens frequently is difficult, often requiring immunocytochemistry to support the diagnosis. Recent reports have proposed the utilization of antibodies to mesothelial cell clone HBME‐1 and thrombomodulin (TM), because they are immunoreactive in MM and less commonly reactive in ACA. Immunoreactivity for the monoclonal antibody CA 19‐9 has been observed in many ACAs and reportedly is absent in MM.

Detection of malignant hematopoietic cells in cerebral spinal fluid previously diagnosed as atypical or suspicious

Involvement of the cerebrospinal fluid (CSF) by hematopoietic malignancies may be difficult to document by morphology alone. In cases with low numbers of cells or ambiguous morphology, the diagnoses of “atypical” or “suspicious” may be used. The significance of these diagnostic terms in this scenario has not been well established.

Melanoma-associated antigen recognized by T cells (MART-1)

HMB‐45, an antibody directed against a premelanosome glycoprotein, has thus far been considered the most specific antibody for the immunocytochemical substantiation of the diagnosis of malignant melanoma (MM). A recently described antigen, MART‐1, is a transmembrane protein that is present in normal melanocytes and widely expressed in MM. Antibodies to MART‐1 have recently become commercially available. Both HMB‐45 and MART‐1 form the basis of ongoing immunotherapy protocols at the National Institutes of Health/National Cancer Institute.

Detection of circulating tumor cells and micrometastases in Stage II, III, and IV breast cancer patients utilizing cytology and immunocytochemistry

Evaluation for circulating tumor cells and bone marrow micrometastases has generated considerable interest due to a potential association with disease recurrence and poor prognosis. In this study, we examined bone marrow and apheresis samples from Stage II, III, and IV patients (n 120) enrolled in various clinical breast cancer trials at the National Institutes of Health/National Cancer Institute. For each patient sample, two Diff‐Quik‐stained cytospins were reviewed for morphology, and approximately 1 × 106 cells were analyzed for the expression of cytokeratins using an avidin‐biotin immunoperoxidase method. Keratin‐positive malignant cells appearing as single cells or in small clusters were detected in bone marrow samples from Stage IV patients only (9/68, 13%) and detected in apheresis samples from both Stage III and IV patients (13/245, 5%). These findings indicate that the combination of cytomorphology with immunocytochemistry can be utilized for the investigation of circulating tumor cells and bone marrow micrometastases, and that positive results appear to correlate with high tumor stage/burden. Diagn. Cytopathol. 2000;22:323–328. Published 2000 Wiley‐Liss, Inc.

Anti‐α‐inhibin

Anti‐α‐inhibin, an antibody directed against a peptide hormone, has been shown to be a useful diagnostic aid in surgical pathology material for the identification of sex cord–stromal neoplasms and recently has been described in adrenocortical carcinoma (ACC). The diagnosis of ACC versus renal cell carcinoma (RCC) may be difficult morphologically, particularly in fine‐needle aspiration (FNA) material. To date, the immunohistochemical distinction of ACC from RCC is based on a panel of antibodies that include vimentin, cytokeratins, and epithelial membrane antigen. However, the reliability of this panel is weakened by inconsistent staining patterns.

Fine-needle aspiration of metastatic clear cell carcinoma of the kidney†

The differential diagnosis of metastatic clear cell carcinoma is broad. To date, there are no specific immunohistochemical markers for renal cell carcinoma (RCC) in general use. Loss of heterozygosity (LOH) at 3p25.5, the von Hippel‐Lindau (VHL) gene locus, is frequent in sporadic clear cell RCC. The authors compared LOH in primary and metastatic RCC through microdissection and the polymerase chain reaction (PCR) to evaluate these techniques as potential diagnostic tools.

Chronic granulomatous disease of childhood: Respiratory cytology

Chronic granulomatous disease (CGD) of childhood is a rare inherited disease in which phagocytic cells fail to produce the normal respiratory burst in response to infectious stimuli, leaving the patient particularly susceptible to infections with bacteria and fungi that produce catalase. Between 1988 and 1993 at the NIH, 58 pulmonary cytology specimens were obtained on 24 CGD patients. The number of specimens per patient ranged from one to 13 with an average of 2.4. The 58 specimens included: 33 bronchoalveolar lavages; one bronchial brushing; 20 lung or pleural mass fine‐needle aspirates; three pleural fluids, and one sputum. Two lung aspirates with insufficient material, five bronchoalveolar lavages performed post‐treatment to confirm clinical resolution of disease, and two bronchoalveolar lavages not submitted for culture were excluded from further analysis.