Frank Vuitch

Salivary duct carcinoma

Background. Salivary duct carcinoma (SDC) is a distinctive salivary gland neoplasm morphologically characterized by intraductal and infiltrating components. Most tumors occur in the major salivary glands and demonstrate a propensity for invasive growth with early regional and distant metastases. Therefore, SDC is regarded as a high‐grade malignancy in the current classification of salivary gland neoplasms.

Hyalinizing Clear Cell Carcinoma of Salivary Gland

We describe 11 patients with a distinctive salivary gland neoplasm. Most of the patients were adult women who presented with a painless mass. Nine tumors arose in minor salivary glands of the oral cavity (82%). Microscopically, they were characterized by the formation of trabeculae, cords, islands, and/or nests of monomorphic clear cells that were glycogen rich and mucin negative and were surrounded by hyalinized bands with foci of myxohyaline stroma. Cells with eosinophilic and granular cytoplasm were also noted. Both cell types showed minimal nuclear pleomorphism and a very low mitotic index. The neoplasms all had infiltrative borders. Immunohisto-chemically, the tumor cells expressed cytokeratins and epithelial membrane antigen, but not S-100 protein and smooth muscle actin. Ultrastructurally, the tumor cells contained abundant glycogen, desmosomes, peripheral tonofilaments, and prominent interdigitating microvilli without actin myofilaments or dense bodies. These im-munohistochemical and ultrastructural findings provide evidence of epithelial differentiation without myoepithelial differentiation. For these tumors, we propose the name, hyalinizing clear cell carcinoma (HCCC). These are low-grade malignant neoplasms. Two patients had ip-silateral cervical lymph node metastases at presentation, but with surgical excision and either preoperative or postoperative radiotherapy in three cases, eight of 10 patients with clinical follow-up are alive and well without evidence of recurrence. The mean clinical follow-up is 3.6 years, with a range of 6 months to 11 years. One patient died as a result of surgery, another died of unrelated causes, and one patient was lost to follow-up.

Computed tomography and magnetic resonance diagnosis of allergic fungal sinusitis

The objective of this study was to describe CT and MR findings in patients with allergic fungal sinusitis (AFS). CT and MR images were examined from 10 patients with histologically proven AFS. All patients demonstrated CT evidence of central sinus high attenuation and T2‐weighted MR signal void corresponding to surgically proven areas of thick inspissated allergic mucin. AFS is a distinct clinical entity with a highly specific radiographic appearance based on CT and MRI.

Allergic aspergillosis: A newly recognized form of sinusitis in the pediatric population

In 1983, Katzenstein, et al. first described a form of noninvasive sinusitis in adults, which was histologically identical to allergic bronchopulmonary aspergillosis, with mucin‐containing eosinophils, Charcot‐Leyden crystals, and fungal elements resembling Aspergillus species. The authors have treated six pediatric patients ages 8 to 16 who had findings typical of allergic Aspergillus sinusitis. All patients presented with nasal polyposis and progressive facial deformity. All patients had computed tomography findings of diffuse expansile sinus disease and four patients had evidence of bony erosion, raising the suspicion of malignancy. At surgery, all were found to have multiple sinuses densely packed with greenish‐black inspissated mucin. Therapy consisted of wide surgical drainage with careful follow‐up and nasal steroids.

Clear cell adenocarcinoma and nephrogenic adenoma of the urethra and urinary bladder: A histopathologic and immunohistochemical comparison

Because of histological similarities between nephrogenic adenomas and clear cell adenocarcinomas of the urinary tract, there is the potential for diagnostic confusion between these two entities. The histopathologic features of 13 nephrogenic adenomas and five clear cell adenocarcinomas of the urethra and urinary bladder are compared in this report, and detailed immunohistochemical staining profiles are provided for these tumors. Only 2 of the 13 nephrogenic adenomas contained clear cells, and these constituted less than 10% of the lesions. In contrast, four of the five clear cell adenocarcinomas contained prominent areas with clear cells. Nephrogenic adenomas generally showed only mild cytologic atypia, whereas four of the five clear cell adenocarcinomas showed severe atypia. A single mitotic figure was identified in only two of the nephrogenic adenomas, whereas the mitotic rate in the clear cell adenocarcinomas ranged from 2 to 14 per 10 high-power fields. None of the nephrogenic adenomas showed evidence of necrosis, but focal necrosis was noted in four of the five clear cell adenocarcinomas. In general, the nephrogenic adenomas and clear cell adenocarcinomas showed negative to weak staining with CK903 but strong staining with AE1, AE3, and Cam 5.2. Variable staining was observed with Brst-3 and antibodies to S-100, CEA (monoclonal and polyclonal), LeuM-1, and CA19.9. Nephrogenic adenomas and clear cell adenocarcinomas were all negative for prostate-specific acid phosphatase (PSAP), prostate-specific antigen (PSA), and estrogen and progesterone receptors (except for two nephrogenic adenomas, which showed only focal weak staining for estrogen receptor). Neither bcl-2 nor c-erbB-2 staining was able to discriminate between the tumors. However, strong staining for p53 was noted in each clear cell adenocarcinoma and in none of the nephrogenic adenomas. MIB-1 positivity in nephrogenic adenomas ranged from 0 to 13 (average of 5.5) per 200 cells, whereas the positive range for clear cell adenocarcinomas was 33 to 70 (average of 47) per 200 cells. In summary, histopathologic features that favor clear cell adenocarcinoma over nephrogenic adenoma include a predominance of clear cells, severe cytological atypia, high mitotic rate, necrosis, high MIB-1 positivity, and strong staining for p53.

Extensive areas of aneuploidy are present in the respiratory epithelium of lung cancer patients.

According to the field cancerisation theory the entire upper aerodigestive tract has been mutagenised, thereby placing the affected individual at risk for the development of one or more cancers. To investigate this concept we studied the respiratory epithelium in lungs bearing cancer, including bronchi, bronchioles and alveoli. After identifying preneoplastic and preinvasive lesions by light microscopy, we determined the DNA content of their nuclei in Feulgen-stained sections using a high-performance digitised image analyser. Archival material from 35 resected cases of non-small-cell lung cancer (NSCLC) was selected, including 16 central tumours (mainly squamous cell carcinomas) and 19 peripheral tumours (mainly adenocarcinomas) and five resected cases of metastatic tumour from extrathoracic primary sites. Of the NSCLCs, 31/35 (89%) were aneuploid, as were 60% of the metastases from extrathoracic sites. Multiple, focal areas of preneoplasia or preinvasive carcinoma were present in the selected cases. The lesions ranged in severity from hyperplasia through metaplasia and dysplasia to carcinoma in situ. Aneuploid preinvasive lesions were not noted in association with the four diploid tumours but were present only when the accompanying NSCLC was aneuploid. With both central and peripheral tumours, aneuploid preneoplastic lesions were more frequent in the peripheral parts of the lung (bronchioles or alveoli) than in the central bronchi. Both the degree and incidence of aneuploidy increased with progressive severity of morphological change. Aneuploidy was not found in preinvasive lesions accompanying the five metastatic cases. Our findings provide strong support for the concept of field cancerisation.

Sinus histiocytosis of pelvic lymph nodes after hip replacement. A histiocytic proliferation induced by cobalt-chromium and titanium.

Six men who had undergone hip replacements for degenerative joint disease or trauma subsequently had radical prostatectomies or cystoprostatectomies with bilateral pelvic lymph node dissections for adenocarcinoma of the prostate or transitional cell carcinoma of the urinary bladder. The hip prostheses implanted in three patients were known to contain cobalt-chromium alloy and titanium. The pelvic lymph nodes ipsilateral to the hip prosthesis in five patients and the bilateral pelvic nodes in the only patient with bilateral hip prosthesis had dark brown or black cut surfaces. These lymph nodes did not contain carcinoma but showed florid sinus histiocytosis characterized by large polygonal histiocytes filling and expanding sinuses and interfollicular regions. The foamy histiocytes contained cobalt-chromium and titanium micropar-ticles by light microscopy, ultrastructure, and energy-dispersive x-ray microanalysis. The lymph nodes uninvolved by the histiocytic reaction lacked the heavy metal microparticles. Four cases were found to have a small number of polyethylene particles, which might have contributed to the histiocytic response. By immunohis-tochemistry, the foamy cells displayed immunoreactivity for lysozyme, α-1-antitrypsin, α-1-antichymotrypsin, and cathepsin D, providing additional support for their histiocytic derivation. To our knowledge, this is the first time that microparticles of cobalt-chromium and titanium that migrate from hip prostheses to pelvic lymph nodes have been shown to elicit a distinctive type of florid sinus histiocytosis. Pathologists should be aware of this characteristic foreign-body tissue response to avoid confusion with other types of sinus histiocytosis or with metastatic carcinoma.

Testicular Tumors in Men with Human Immunodeficiency Virus

During a 2-year period 5 men positive for the human immunodeficiency virus (HIV) presented with 6 testis tumors among a total of 3,015 men seen at our hospital acquired immunodeficiency syndrome (AIDS) clinic. This testis tumor incidence of 0.2% is 57 times that of the United States average of 3.5 cases per 100,000 men. Two patients were only HIV positive and 3 others already had AIDS-related complex for 2 to 15 months at the time of tumor diagnosis. Tumor histology was mixed germ cell tumor in 4 patients, pure seminoma in 1 and Burkitts lymphoma in 1. Patients underwent routine staging evaluations. Three patients had low stage mixed germ cell tumor (clinical stage 1 or 2A) and underwent retroperitoneal lymphadenectomy, which revealed pathological stage 1 or 2A disease in 1 and 2, respectively. These patients did not receive adjuvant chemotherapy. Two patients had advanced mixed germ cell tumor (clinical stage 2C) or Burkitts lymphoma (clinical stage 4) and received combination chemotherapy from the onset. Outcome was evaluated with regard to progression of HIV disease and tumor status. The 2 patients who were only HIV positive remained so for 9 and 48 months. The 3 patients with AIDS-related complex had progression to AIDS within 1 to 9 months and 2 of these patients died 1 1/2 and 7 months after tumor diagnosis. All 3 patients with resected low stage disease had tumor recurrence within 1 to 9 months and were begun on platinum-based combination chemotherapy. The risk of false low clinical staging and early tumor progression may be higher in HIV positive men than in other testis tumor patients. Patient ability to tolerate chemotherapy and to obtain a satisfactory tumor response appeared to be primarily related to lack of progression of HIV disease to frank AIDS.

Loss of heterozygosity and microsatellite alterations in p53 and RB genes in adenoid cystic carcinoma of the salivary glands

Adenoid cystic carcinomas (ACC) constitute approximately 20% of malignant salivary gland tumors. Several histological types of ACC are recognized and may coexist in a single tumor. The authors divided ACC into lower grade (tubular and cribriform subtypes) and higher grade (trabecular and solid) subtypes. A preliminary analysis of 10 ACCs showed a relatively high incidence of loss of heterozygosity (LOH) at the p53 and RB genes and low or absent K-ras mutations and LOH at chromosomal loci 3p, 5q, 8p, and 9p. From 21 tumors, the authors carefully microdissected and analyzed 36 subtype foci. Three interrelated pieces of evidence indicate that the relatively poor prognosis higher grade subtype arises from one or more of the lower grade subtypes via progression events associated with mutations in the p53 or RB genes. First, the number of mutations (both LOH and microsatellite alterations) at either gene is greater in higher grade foci than in lower grade foci; second, multiple mutations (two and occasionally three) are present in only higher grade foci; and third, when lower and higher grade foci are present in the same tumors, identical mutations plus other mutations are present in the corresponding higher grade foci. These findings suggest that molecular analyses of ACCs may provide information of prognostic importance.

Telomerase activity in benign and malignant thyroid diseases.

BACKGROUND Telomerase, an enzyme associated with cellular immortality, is expressed by most malignant cells and is inactive in most normal somatic cells, with the excitation of proliferative stem cells, male germ cells, and activated lymphocytes. The measurement of telomerase activity in clinically obtained tissue samples may provide useful information as both a diagnostic and prognostic marker. In this study, we sought to determine whether telomerase activity might prove helpful in the assessment of benign and malignant thyroid tumors. METHODS A modified, semiquantitative polymerase chain reaction-based telomeric repeat amplification protocol assay was used for detection of telomerase activity in 59 samples obtained at thyroidectomy, including 15 thyroid cancers, 22 benign thyroid diseases, and 22 adjacent normal thyroid tissues. RESULTS Four of 13 differentiated thyroid carcinomas (30%) and 2 of 2 medullary carcinomas (100%) expressed telomerase activity. Unexpectedly, we also detected activity in 3 of 22 (14%) adjacent normal thyroid tissues and 6 of 22 (28%) benign thyroid diseases. Pathologic review of the telomerase-positive benign specimens revealed that many contained extensive lymphoid infiltrates with germinal centers (six of nine, 67%), as did two of four telomerase-positive papillary carcinomas. CONCLUSIONS In contradistinction to other epithelial carcinomas, telomerase does not appear to be frequently reactivated in differentiated thyroid carcinomas.