Arnold H. Szporn

Survival with colorectal cancer in ulcerative colitis. A study of 102 cases.

ObjectiveThis study was undertaken to correlate postoperative survival of patients with ulcerative colitis-associated colorectal cancer with the stage, configuration, size, and mucin content of the tumor. Summary Background DataThe factors influencing prognosis in colorectal cancer in the general population are well accepted, but less is known about their influence in cases of colorectal cancer associated with ulcerative colitis. MethodsThe authors reviewed the records of 102 patients with ulcerative colitis-associated colorectal cancer admitted to The Mount Sinai Hospital between 1959 and 1988. Tumors were classified on independent pathologic review according to histologic stage, configuration, size, and mucin content. Comparisons among survival curves were tested by the generalized Wilcoxon test. Cox regression models were used to examine the joint effects of selected clinicopathologic features on postoperative survival rates. ResultsComplete follow-up was obtained for 93 patients (92%). Overall 5-year actuarial survival was 52%. When factors were analyzed one at a time, survival was significantly poorer among patients with advanced cancer stage, larger tumor size, infiltrating and ulcerating configuration, and high mucin concentration. On multivariate analysis by the Cox regression model, however, only cancer stage emerged as a factor independently predicting survival. ConclusionsFor colitis-associated colorectal cancers, as for noncolitic cancers, histologic stage is the most important variable determining postoperative survival. The distribution of stages in our series and the survival rates within each stage did not differ appreciably from the distributions and survival rates reported for noncolitic colorectal cancers.

Immunocytochemical detection of XIAP in body cavity effusions and washes.

Body cavity effusions may be the first manifestation of malignancy or of recurrence or relapse. We surveyed effusions and washes for expression of X-linked inhibitor of apoptosis (XIAP), a potent constituent of the inhibitor of apoptosis (IAP) family of proteins. IAPs prevent apoptosis by blocking the activation of caspases, thereby preventing caspase-mediated cell degradation. Elevated expression of XIAP could be an underpinning of relapse and/or resistance to apoptosis-inducing cancer therapy. We performed an immunocytochemical survey of XIAP expression in cell blocks from benign and malignant body cavity effusions and washes. In all, 116 alcohol-fixed, formalin postfixed paraffin-embedded cell block specimens from 82 pleural effusions, 22 ascites, 11 pelvic/peritoneal washes and one pericardial effusion were evaluated immunocytochemically with monoclonal anti-XIAP (#610763, BD Biosciences, San Jose, USA) 1:250, 4°C × 72 h, and developed using EnVision-Plus reagents (Dako) and diaminobenzidine as chromagen. Particulate cytoplasmic staining was considered positive. The prevalence of staining for specific malignancies varied with the tissue of origin as follows: ovarian (13/13, 100%); lung (9/11, 82%), breast (6/13, 46%); gastric (4/7, 57%), colon (0/4, 0%), pancreas (2/3, 67%), gallbladder (1/1, 100%), fallopian tube (1/3, 33%), endometrial (6/7, 86%), mesothelioma (4/5, 80%), carcinoma of unknown primary (5/5, 100%) and hematopoietic malignancies (3/9, 33%). Overall, 54 out of 81 (67%) malignant effusions displayed XIAP positivity. Benign effusions (n=35) were virtually XIAP-negative except for two cases (6%) in which histiocytes showed moderate staining. Weak nonspecific staining was sometimes noted in inflammatory cells or histiocytes. XIAP immunostaining, when strong, allows for ready distinction of malignant from benign and reactive cell populations. Strong XIAP staining was most prevalent in ovarian carcinomas and less prevalent in mammary carcinomas. The degree of XIAP staining of tumor cells may be a means of identifying the most therapy-resistant cases (ie, those with strong XIAP expression), and allow additional triaging to XIAP-blocking drugs presently being developed and clinically tested.

A comparative study of 200 fine needle aspiration biopsies performed by clinicians and cytopathologists.

Fine needle aspiration (FNA) biopsy is a useful tool in the diagnosis and management of suspicious masses. Most FNA biopsies of palpable masses can be performed without radioguidance by either clinicians or cytopathologists; however, it is unclear if there is a difference in the diagnostic yield of the procedure based on who performs the FNA. We reviewed the FNA biopsy results of 200 patients presenting with head and neck masses to a tertiary care center from 2003 to 2004. One hundred FNA biopsies were performed by clinicians and 100 performed by cytopathologists. Seventy‐one underwent subsequent surgical biopsy or definitive surgery. Results of the FNA biopsies performed by the clinicians and the cytopathologists were compared based on the percentages of FNAs that were diagnostic, suspicious/suggestive, and nondiagnostic. Additionally, the pathology results of the 71 surgical biopsies or resections were compared with the preoperative FNA results. Of the 100 FNA biopsies performed by cytopathologists, 83% were diagnostic, 10% were suspicious/suggestive, and 7% were nondiagnostic. Of the 100 FNA biopsies performed by clinicians, 24% were diagnostic, 43% were suspicious/suggestive, and 33% were nondiagnostic. Cytopathologists achieved significantly better results (P < .0001, two‐tailed t‐test). Of the 71 cases with surgical follow up (50 by cytopathologists and 21 by clinicians), 94% of cases performed by cytopathologists and 67% of those performed by clinicians show agreement with final surgical pathology results. Overall, the FNAs performed by cytopathologists show significantly better diagnostic accuracy (P = .0002134, two‐tailed t‐test). FNA provides valuable information in the workup of suspicious head and neck masses. Cytopathologists may achieve significantly better results.

Cellular swirls in fine needle aspirates of papillary thyroid carcinoma: a new diagnostic criterion.

No single cytologic feature is specifically diagnostic for papillary thyroid carcinoma. We report herein the presence of swirl-like cellular aggregates in fine needle aspirates of papillary thyroid carcinoma but not in other thyroid entities. Cellular swirls are defined as concentrically organized aggregates of tumor cells in which many of the most peripherally situated cells have ovoid rather than round nuclei that are oriented perpendicular to the radius of the swirl. One hundred Papanicolaou- and/or Diff-Quik-stained FNAs of the thyroid diagnosed as papillary carcinoma, including seven fine needle aspirates of cervical lymph nodes showing metastatic papillary carcinoma, with or without cell blocks, were reviewed for the presence of cellular swirls. An additional 100 thyroid FNAs, similarly stained and prepared, diagnosed as nodular goiter, Hashimotos thyroiditis and follicular neoplasm were also reviewed for the presence of cellular swirls. Cellular swirls were easily observed at screening magnification and confirmed at high magnification. Seventeen of 100 FNAs (17%) of papillary carcinoma contained cellular swirls. No cases diagnosed as nodular goiter, Hashimotos thyroiditis or follicular neoplasm contained these structures. Thirteen cases with swirls had histologic follow-up. These comprised seven papillary carcinomas with classical histopathology, two designated ‘differentiated papillary carcinoma,’ two with follicular variant histopathology; one with a minor component of follicular variant histopathology; one papillary carcinoma metastatic to a cervical lymph node with classic histopathology. Swirls occurred in cases with relatively little pleomorphism, or in well-differentiated regions of papillary carcinoma that also displayed less well-differentiated components. Cellular swirls are a finding that is highly specific to papillary thyroid carcinoma. They are easily seen at screening magnification. Their presence in a FNA specimen may be helpful in cases where classic criteria for papillary thyroid carcinoma are scarce, particularly in well-differentiated papillary thyroid carcinoma. While the size and scope of this study are insufficient to conclude that cellular swirls alone are diagnostic of papillary thyroid carcinoma in the absence of other criteria, we believe these structures should be added to the list of diagnostic criteria.

Atypical Chédiak-Higashi syndrome with attenuated phenotype: three adult siblings homozygous for a novel LYST deletion and with neurodegenerative disease.

BackgroundMutations in LYST, a gene encoding a putative lysosomal trafficking protein, cause Chédiak-Higashi syndrome (CHS), an autosomal recessive disorder typically characterized by infantile-onset hemophagocytic syndrome and immunodeficiency, and oculocutaneous albinism. A small number of reports of rare, attenuated forms of CHS exist, with affected individuals exhibiting progressive neurodegenerative disease beginning in early adulthood with cognitive decline, parkinsonism, features of spinocerebellar degeneration, and peripheral neuropathy, as well as subtle pigmentary abnormalities and subclinical or absent immune dysfunction.MethodsIn a consanguineous Pakistani kindred with clinical phenotypes consistent with attenuated CHS, we performed SNP array-based homozygosity mapping and whole gene sequencing of LYST.ResultsWe identified three individuals homozygous for a novel six base pair in-frame deletion in LYST (c.9827_9832ATACAA), predicting the loss of asparagine and threonine residues from the LYST transcript (p.Asn3276_Thr3277del), and segregating with the phenotype in this family.ConclusionsWe further characterize the neurologic features of the attenuated form of CHS, and discuss pathophysiologic mechanisms underlying the neurodegenerative components of CHS. Attenuated CHS is phenotypically heterogenous and should be considered when young adults develop neurodegenerative disease and have pigmentary abnormalities. We briefly discuss surveillance and management of patients with CHS-related neurodegeneration.

Ultrasonic mucosal proctectomy in patients with ulcerative colitis.

A technique for performing mucosal proctectomy in patients with ulcerative colitis using ultrasonic fragmentation is described. Twenty-eight patients undergoing colectomy and ileoanal anastomosis were studied. Removal of the mucosal layer of the distal rectum was performed using a titanium probe vibrating at 23 kHZ with an amplitude of 300 microns. This method produces complete mucosal destruction and the resulting debris and irrigating fluid is removed through the hollow central portion of the probe. Healing of the ileoanal anastomosis does not appear to be adversely affected by the use of this technique. Because ultrasonic fragmentation is not dependent on the integrity of the submucosal plane, it may be advantageous in those cases in which severe inflammation and submucosal scarring make manual dissection of the rectal mucosa difficult to perform.

Wegener granulomatosis presenting as renal mass

Wegener granulomatosis involves both the respiratory and genitourinary systems. Kidney lesions are invariably focal. Wegener granulomatosis only rarely affects other genitourinary organs and, until now, has not been described as a mass in the kidney. In the case presented, the diagnosis was unknown before surgery, though clinically suspected. The management, which included nephrectomy and chemotherapy with cyclophosphamide (Cytoxan) and prednisone, caused a marked improvement, and the patient was discharged in stable condition.

ras and c-myc protein expression in colorectal carcinoma

This study was performed to determine the correlation of tumorrasand c-myconcogene expression with clinical and prognostic variables in patients prone to develop colorectal cancer. One hundred eighteen patients with colorectal cancer were studied; mean age was 40 years. Fifty-three were young patients (age 40 or less), 49 had ulcerative colitis, and 16 had multiple polyposis coli. Immunoperoxidase stains of paraffin-embedded cancer sections were performed for the c-mycandrasproteins.rasstaining was found to correlate with Dukes stage and prognosis. Patients with tumors negative forrasprotein stain had an actuarial five-year survival of 61 percent versus 44 percent for those tumors with a positive stain (P<0.05). This correlation was not seen with the c-mycstain. Positiverasoncogene stain appears to be a useful indicator of advanced stage and poor prognosis in colorectal cancer occurring in cancer-prone patients.

Primary CNS plasmablastic lymphoma: Report of a case with CSF cytology, flow cytometry, radiology, histological correlation, and review of the literature

Plasmablastic lymphoma (PBL) is a rare subtype of diffuse large B cell lymphoma and commonly presents as an oral mass in HIV patients. Extraoral PBL has been reported, including one case of primary central nervous system PBL (PCNSPBL). The cytological features of PBL have been described, including cerebrospinal fluid (CSF) cytology findings for secondary CNS involvement by PBL. The etiology of PCNSPBL is still unknown. We report here the CSF cytology of a PCNSPBL, which shows a hypercellular specimen composed of markedly atypical, singly dispersed plasmacytoid cells with frequent abnormal mitoses and binucleation. The neoplastic cells are positive for CD138. Flow cytometry of the CSF specimen demonstrates a monoclonal neoplastic cell population, which is CD138 positive, kappa light chain positive, lambda light chain negative, and CD19 negative. Molecular analysis and immunohistochemical stains on a tissue biopsy confirmed the diagnosis and reveal concurrent infections with Epstein‐Barr virus and human polyomavirus JC virus. Clinical and radiological correlations are reported, and the literature is reviewed. To the best of our knowledge, this is the first case report for CSF cytology of a PCNSPBL, demonstrating the utility of the cytological examination in the triage and diagnosis of this disease. Because of its dismal prognosis, it is critical for cytopathologists to be aware of the entity and recognize the neoplastic cells in CSF specimen. This report also emphasizes the importance of clinical and radiological correlation in the diagnosis of this lethal disease. Diagn. Cytopathol. 2011.

Cytologic findings in the differential diagnosis of C-cell hyperplasia and medullary carcinoma by fine needle aspiration. A case report.

BACKGROUND The cytologic features of C-cell hyperplasia of the thyroid have not been previously addressed in the literature. We describe the first case, to our knowledge, of C-cell hyperplasia that was suggested by fine needle aspiration. CASE Cellular material was obtained from a nonnodular region of the thyroid gland in a 67-year-old male with chronic diarrhea, unexplained elevated serum calcitonin, no clinically detectable thyroid mass and no known medical or family history of an endocrine disorder. Aspiration yielded a scant bimodal cell population composed of benign follicular cells and a second population of larger cells, later confirmed as C-cells via immunohistochemistry. Although the diagnosis of medullary carcinoma was entertained, the absence of a discrete mass clinically and the presence of two interspersed, distinct cell populations suggested the alternate diagnosis, C-cell hyperplasia, which was confirmed by subsequent thyroidectomy. CONCLUSION C-cell hyperplasia can mimic medullary carcinoma biochemically, and this case suggests the possible role of fine needle aspiration of the thyroid to distinguish between the two. In patients with elevated serum calcitonin and absence of a discrete thyroid nodule, the finding of clusters of calcitonin-positive cells intermixed with normal follicular cells by fine needle aspiration may provide a means of making a presurgical diagnosis of C-cell hyperplasia.