Proliferative activity in invasive breast carcinoma: a comprehensive comparison of MIB-1 immunocytochemical staining in aspiration biopsies to image analytic, flow cytometric and histologic parameters.

OBJECTIVE: To use MIB-1 antibody to assess proliferative activity in fine needle aspiration (FNA) samples of invasive breast carcinoma and compare these results to multiple other measures of proliferative activity. STUDY DESIGN: FNA slides from 62 patients with invasive breast carcinoma were subjected to staining with MIB-1. Quantitative MIB-1 values were compared to image analytic proliferative fractions (IPF) obtained from the same FNAs. MIB-1 values were also compared to flow cytometric S-phase fractions (SPF) and S + G2/M-phase fractions (FPF) and to histologic assessment of mitotic count (MC) in resected tumors. RESULTS: MIB-1 values, IPF, SPF, FPF and MC were suitable for evaluation in 55, 53, 50, 50 and 56 cases, respectively. MIB-1 values showed good correlation with IPF in FNAs (correlation coefficient = .57, P <.00001). MIB-1 values also showed correlation with SPF (correlation coefficient =.447, P = .003), FPF (correlation coefficient = .325, P = .023) and MC (correlation coefficient = .402, P = .01) in resected tumors. CONCLUSION: This study supports the use of MIB-1 values obtained from FNA samples for assessment of proliferative activity in invasive breast carcinoma, based on correlation of these values with multiple other parameters of proliferative activity. Assessment of these values can play a role in predicting prognosis and in selecting patients with invasive carcinoma of the breast for preoperative or adjuvant chemotherapy.

Cell proliferation in the growing human heart: MIB-1 immunostaining in preterm and term infants at autopsy.

Few studies of human cardiac myocyte proliferation in the perinatal period have been conducted. We measured the proliferative activity of left ventricular myocytes in tissue obtained at autopsy in three surgically induced abortuses, 20 preterm infants with gestational ages ranging from 12 to 35 weeks, eight term infants with ages ranging from 1 day to 11 months, and five adults. The preterm infants lived less than 24 h, thus simulating the in utero condition of developing hearts. To assess the proliferative activity of the myocytes, we measured immunoreactivity using the monoclonal antibody MIB-1 against the recombinant Ki-67 nuclear antigen. Immunostained sections were examined by light microscopy, and the results expressed as a staining index (SI) of 0-3, according to the percentage of positively stained myocyte nuclei. Myocyte proliferative activity remained constant during the early preterm period and decreased in the late preterm and early postterm periods. Adult myocytes, regardless of cardiac weight, did not reveal proliferative activity as assessed by immunostaining. This proliferation pattern is consistent with findings in most earlier studies in animal models.

Relationship between Epstein-Barr virus and lymphoepithelioma-like carcinoma of the lung: a clinicopathologic study of 6 cases and review of the literature.

Lymphoepithelioma-like carcinoma (LELC) is a rare form of lung cancer, usually encountered in Chinese patients. Similar to nasopharyngeal carcinoma, LELC of the lung is strongly associated with Epstein-Barr virus (EBV) infection in Asian patients, but there is controversy over whether an association exists in patients from Western countries. To determine whether such a relationship exists, we retrospectively studied 6 cases of primary LELC of the lung, all of which were in Western patients. There were 4 men and 2 women, ranging in age from 49 to 75 years. The tumors ranged from 1 to 4.5 cm in diameter. Four patients had stage I disease, 1 had stage IIb disease, and 1 had stage IIIa disease. All patients are alive without evidence of disease with a follow-up of 18 to 30 months. Formalin-fixed, paraffin-embedded tissue was stained with hematoxylin-eosin for routine evaluation and immunostained for keratin and leukocyte common antigen (LCA). LCA staining was performed to exclude large-cell lymphoma. Immunoperoxidase staining (1:500 clone CS1-4; Dako, Carpinteria, CA) and in situ hybridization were performed to detect EBV. Tumors consisted of solid nests of undifferentiated tumor cells in a syncytial arrangement surrounded by heavy lymphoplasmacytic infiltrate. Tumor cells stained positively for keratin but negative for LCA. All 6 cases were negative for EBV, suggesting no association between EBV and LELC in the Western population.

Aspiration biopsy findings in amyloid tumor of the cervical vertebra. A case report.

BACKGROUND: The differential diagnosis of destructive lytic lesions of the spine includes amyloid tumors. The diagnosis of amyloid tumor with fine needle aspiration biopsy (FNA) is challenging. Previous reports of FNA of osseous amyloid tumors have detailed the cytologic appearance of amyloid along with lymphocytes, plasma cells and histiocytes, occasionally multinucleate or forming granulomatous lesions. CASE: An 84-year-old man presented with neck pain. Radiologic studies showed a destructive, lytic lesion of C-6, with a large, soft tissue mass. FNA yielded many acellular smears containing abundant amyloid that was confirmed with special stains of corresponding tissue cores and subsequent surgical biopsies. CONCLUSION: Osseous amyloid tumors are destructive, lytic lesions that mimic other processes. Amyloid can be distinguished from other substances in FNA samples and amyloid tumor identified, even when amyloid is present without typical cellular components.

Aspiration biopsy of osseous metastasis of retroperitoneal paraganglioma. Report of a case with cytologic features and differential diagnostic considerations.

BACKGROUND: Paragangliomas are uncommon tumors, only 10% of which are malignant, as evidenced by metastatic disease. It is rare for paraganglioma to present with symptomatic osseous metastases. CASE: A retroperitoneal paraganglioma presented in a 52-year-old man as painful metastases in the rib and vertebrae. Fine needle aspiration (FNA) of a lumbar vertebral lesion showed cells arranged singly and in loose clusters with fragile, vacuolated or finely granular cytoplasm, marked anisonucleosis and mitoses. Rare zellballen-type structures and intranuclear inclusions were present. Immunohistochemical studies of a subsequent FNA core biopsy of the retroperitoneal mass showed strong immunoreactivity with chromogranin and negative staining for keratin; that was helpful in differentiating this tumor from others in the differential diagnosis. CONCLUSION: The cytologic diagnosis of paraganglioma is difficult as these tumors exhibit a plethora of features that overlap those of many other neoplasms. The diagnosis can be confirmed with appropriate immunohistochemical studies of corresponding core biopsies.

Cryptococcal osteomyelitis. Report of a case with aspiration biopsy of a humeral lesion with radiologic features of malignancy.

BACKGROUND: Osteomyelitis due to Cryptococcus neoformans typically exhibits lytic lesions on radiographs. Extensive periosteal reaction is an uncommon feature. CASE: A 68-year-old man presented with pain and swelling in the left elbow. Radiologic studies exhibited a lytic humeral lesion with extensive periosteal reaction, interpreted as a malignant neoplasm. Fine needle aspiration biopsy (FNA) revealed abundant cryptococcal organisms. CONCLUSION: Cryptococcus is an uncommon cause of lytic osseous lesions that may mimic malignant neoplasms. Extensive periosteal reaction may support a radiologic diagnosis of primary osseous malignancy in rare cases. FNA with examination of Diff-Quik-stained slides may be employed for distinguishing cryptococcal osteomyelitis from malignant tumors and for prompt identification of the organisms.

Low-grade intraosseous osteosarcoma with prominent lymphoid infiltrate.

Low-grade intraosseous osteosarcoma is an uncommon and well-differentiated osteosarcoma with a good prognosis. We report a proximal tibial low-grade intraosseous osteosarcoma with a prominent intratumoral lymphoid infiltrate, which led to an initial diagnosis of probable malignant lymphoma. The importance of this infiltrate, which exhibited reactive features on flow cytometric studies, is not known. Our patient is free of tumor 1 year after limb salvage surgery, without hematologic or lymphoid abnormalities.

Malignant chondroblastoma presenting as a recurrent pelvic tumor with DNA aneuploidy and p53 mutation as supportive evidence of malignancy.

We report a rare case of malignant chondroblastoma, which presented in a 47-year-old man as a recurrent tumor, 18 years following wide excision of a typical pelvic chondroblastoma. Radiologic studies of the recurrent tumor showed a large, lytic, destructive lesion of the right pelvic bones and femur, with a pathologic fracture of the latter, a large pelvic soft tissue mass, and multiple pulmonary metastases. Biopsy tissue showed typical features of chondroblastoma, but also increased nuclear atypia, hyperchromasia, and pleomorphism, compared to the original tumor, and, most significantly, abnormal mitotic figures. Immunohistochemical studies of the recurrent tumor revealed p53 mutation and extensive proliferative activity, and flow cytometric studies showed DNA aneuploidy, none of which was present in the original tumor. The patient received chemotherapy and radiation, but died of disease eight months after presentation. We also review chondroblastoma in general, to assign this unusual lesion to a tumor subtype.

Oncocytic mucoepidermoid carcinoma of the trachea.

We report a rare case of an oncocytic mucoepidermoid carcinoma of the trachea, which presented in a 78-year-old woman with hemoptysis. Oncocytic cells comprised the majority of this low-grade lesion and demonstrated granular cytoplasmic phosphotungstic acid-hematoxylin staining as well as strong immunohistochemical reactivity to antimitochondrial antibody. Most tracheobronchial tumors with oncocytic change are carcinoid tumors. To our knowledge, this is the first oncocytic mucoepidermoid carcinoma of the trachea reported. This diagnosis was facilitated by histochemical and immunohistochemical studies.

Detection of p53 protein accumulation in sputum and lung adenocarcinoma associated with indoor exposure to unvented coal smoke in China.

Lung cancer in Xuan Wei (XW), China has been linked to exposure to unvented coal smoke and adenocarcinoma, especially bronchioloalveolar carcinoma, is most common. p53 mutations occur commonly in lung cancers and usually generate detectable levels of p53 protein accumulation. Sputum is noninvasive to collect and ideal for screening p53 abnormalities. p53 protein accumulation was detected by immunohistochemistry in lung tumors and sputa from XW lung cancer patients to determine (1) the role of p53 in lung pathogenesis, and (2) feasibility of detecting p53 protein accumulation in sputum, p53 protein accumulation was detected in 73% (22/30) of lung adenocarcinomas from XW females exposed to coal emissions and significantly higher than the control cases (33%, p < 0.05). In sputum, we detected p53 overexpression in tumor cells in 54% (13/24) of XW cases and also in dysplastic cells (50% or 4/8). These findings suggest that p53 abnormalities is important in XW lung cancer etiology.

Oncocytic mucoepidermoid carcinoma of the salivary glands.

Two parotid mucoepidermoid carcinomas with predominant oncocytic features were initially assessed on frozen section. Because of extensive oncocytic change, it was inferred that the lesions were most likely benign. Permanent sections revealed low-grade mucoepidermoid carcinoma with prominent oncocytic change (in more than 75% of the neoplasms) in both cases. Review of 48 additional consecutive cases of mucoepidermoid carcinoma of the salivary glands revealed prominent oncocytic change (accounting for 60% of the neoplasm) in one high-grade lesion. Phosphotungstic acid-hematoxylin stains revealed strong granular cytoplasmic staining in the oncocytic elements; immunohistochemical stains for antimitochondrial antibodies also showed intense immunoreactivity in these cells. Oncocytic change is not typically a prominent feature of mucoepidermoid carcinoma of the salivary glands, and to our knowledge, only three such cases have been reported previously. Because most salivary gland lesions with oncocytic change are benign, it is important to distinguish mucoepidermoid carcinoma from other entities that may show prominent oncocytic change. We report three additional examples of this rare lesion, two low-grade tumors and one high-grade tumor, and review our experience with oncocytic change in mucoepidermoid carcinoma of the salivary glands.

Osseous Hodgkin disease.

BACKGROUND: Hodgkin disease rarely presents as an osseous lesion, and the majority of patients are found at staging to have concurrent disease in lymph nodes. Many cases of osseous Hodgkin disease have been misdiagnosed on initial biopsy. METHODS: All cases of Hodgkin disease diagnosed by open bone biopsy at the Mayo Clinic were identified. These included patients with primary osseous tumors, those presenting with multiple sites of involvement (with osseous lesions), and those with recurrence in bone. Recut sections were subjected to immunohistochemical stains to confirm the diagnosis. Clinical data and follow-up information were obtained from patients' charts. RESULTS: Twenty-five patients (15 males and 10 females with an average age of 37 years) with osseous Hodgkin disease were identified during the years 1927-1996. Three patients had solitary, osseous tumors and two had primary, multifocal, osseous Hodgkin disease without involvement of nonosseous sites. Twelve patients who presented with lesions in osseous sites also had nonosseous tumors detected at staging, and 8 patients had recurrent Hodgkin disease that presented in bone. The majority of patients with primary and recurrent tumors presented only with bone pain; >50% of patients with concurrent osseous and nonosseous disease also had B-type symptoms. Nearly all lesions were in the axial and proximal appendicular skeleton. Radiographic features included osteosclerotic, osteolytic, and mixed lytic/sclerotic patterns. Cortical destruction, periosteal new bone formation, and soft tissue masses were present in 50% of cases. The histologic diagnosis of osseous Hodgkin disease occasionally was problematic; osteomyelitis was the most frequent misdiagnosis. Immunohistochemical stains revealed expression of CD15 and CD30 in neoplastic cells (which were negative for CD45 and B-cell and T-cell antigens) in all but two cases. Involved lymph nodes typically exhibited nodular sclerosis Hodgkin disease. Three patients with primary solitary osseous Hodgkin disease received radiation treatment only; at last follow-up 2 patients were alive at 22 months and 10 years, respectively. Patients with concurrent osseous and nonosseous tumors exhibited a 60% overall survival rate, but at last follow-up all 4 patients diagnosed after 1986 still were alive; those with Hodgkin disease that recurred as osseous lesions had a 60% survival rate at 8 years, but only 1 of the 5 patients diagnosed since 1984 had died of disease. CONCLUSIONS: Osseous Hodgkin disease typically presents with bone pain, and the majority of patients have concurrent nonosseous lesions detected at staging. Radiographic features of osseous Hodgkin disease vary but indicate an aggressive malignant process. The histologic diagnosis may be problematic; immunohistochemical stains aid in establishing the diagnosis of Hodgkin disease in bone. Survival of patients with osseous Hodgkin disease has been found to be good for the last 10 years.

Tall cell variant of papillary thyroid carcinoma: cytologic features and differential diagnostic considerations.

The cytologic features of the tall cell variant (TCV) of papillary thyroid carcinoma may be confused with those of other thyroid neoplasms with different prognoses and treatment modalities. Elucidation of the cytomorphology of this variant would be useful in planning treatment for this fairly aggressive variant of papillary carcinoma. The cytologic features of 20 cases of TCV were compared with those of 23 cases of the usual variant (UV) of papillary thyroid carcinoma and of 10 Hürthle-cell neoplasms (HCN). After a set of features was defined, the efficacy of employing it to distinguish TCV from UV and HCN was assessed by three cytopathologists (J.D.T., I.R., and M.O.), was independently examined 15 unknown cases selected by the first author. Aspirates of TCV showed some specific cytologic features which included large cell size with abundant granular cytoplasm and variably sized nuclei with granular chromatin. The cells were sometimes columnar, but more often were polygonal, and prominent cytoplasmic borders were present in 50% of cases. Intra-nuclear inclusions were more prominent in TCV than in UV. There was some overlap in the cytomorphology of some TCV and UV cases, and variable numbers of cells with UV features were encountered in TCV cases. Employing the cytologic features of TCV listed above, three cytopathologists examined the unknown cases, which included 7 cases of TCV, 4 cases of UV, and 4 cases of HCN. TCV was recognized as such by all three cytopathologists in 6 of 7 cases, and all UV and HCN were correctly typed by all three examiners. The cytologic features of TCV are sufficiently distinctive to enable separation from HCN and most cases of UV. Although the diagnosis of TCV may be rendered employing fine-needle aspiration biopsy, material, this diagnosis should be limited, in our opinion, to specimens which contain at least 30% of cells with typical TCV features.

Lesions of the bones of the hands and feet.

Neoplasms and their simulators in the bones of the hands and feet include the majority of those found in other skeletal sites, and a disproportionate number of some. We examined the clinical, radiologic, and pathologic features of 240 lesions of the hand and foot bones. Benign tumors and lesions including reactive and reparative conditions comprised 203 cases. The largest single category of neoplasms was that with cartilaginous differentiation, with enchondromas (29 cases) and chondrosarcomas (15 cases) the most common. Noncartilaginous malignant tumors were infrequent and displayed typical radiologic and pathologic features. Florid reactive periostitis, bizarre parosteal osteochondromatous proliferations, and giant cell reparative granulomas made up a larger percentage of lesions in these locations than in other skeletal sites. Lesions of the bones of the hands and feet may frequently be biopsied or treated at hospitals without large orthopedic tumor services. Thus, it is important for the surgical pathologist to be aware of the frequency and characteristics of lesions which may present in these sites.

Localized thymic Langerhans' cell histiocytosis and its relationship with myasthenia gravis. Immunohistochemical, ultrastructural, and cytometric studies.

OBJECTIVE: It has been suggested that localized Langerhans cell histiocytosis may represent an exaggerated form of a proliferative process that has been reported in a few patients with myasthenia gravis. To evaluate the relationship between thymic Langerhans' cell proliferation and myasthenia gravis, we analyzed a rare case of localized thymic Langerhans' cell histiocytosis and examined thymic Langerhans' cell distribution in myasthenic and control patients. DESIGN: Immunohistochemical, ultrastructural, and image cytometric DNA analyses were performed on the index case. Immunostaining for S100 was performed on 20 additional thymuses, 10 from patients with myasthenia gravis and 10 from control patients. RESULTS: Immunohistochemical studies revealed no increase in Langerhans' cells in the surrounding thymic tissue of the index case. No difference was found between the number of Langerhans' cells in the remaining thymuses of myasthenia patients compared with the control group, and no micronodular proliferations were identified in either group. CONCLUSIONS: Localized thymic Langerhans' cell histiocytosis is an unusual lesion that is associated with myasthenia gravis in some patients. In the few cases reported at present, however, the lesion does not appear to be related pathogenetically to myasthenia gravis.

Tall cell variant of papillary thyroid carcinoma: a reassessment and immunohistochemical study with comparison to the usual type of papillary carcinoma of the thyroid.

A review of 92 consecutive cases of papillary thyroid carcinoma diagnosed at The Methodist Hospital revealed 11 tall cell variant (TCV) cases in nine women and two men. There was a greater average age and larger tumor diameter of TCV cases compared with papillary thyroid carcinoma of the usual type (UPTC), but these differences were not statistically significant. Extrathyroidal extension of tumor was noted in nine of 11 TCV cases and was intraoperatively evident in five cases. The presence of extrathyroidal extension represented a statistically significant difference between TCV and UPTC (p = 0.0001) in a multivariate stepwise logistic regression analysis, with controls for variables of age, sex, tumor size, and lymph node metastases. In 11 TCV patients, tumor recurrence was present in two cases, and there was one tumor-associated death with 1 to 4 years of follow-up. Immunohistochemical stains for thyroglobulin, vimentin, keratins, and Leu-7 were positive in all TCV cases and in 16 of 16 UPTC. Immunoreactivity with antibodies to Leu M1 antigen, a myelomonocytic marker included in cluster designation group (CD 15), which is present in many adenocarcinomas, was present diffusely in all TCV, in contrast to UPTC (with sparse immunostaining in only one of 16 cases). Immunoreactivity with antibodies to ZC-23, an anti-carcinoembryonic antigen (CEA) monoclonal antibody with cross-reactivity to nonspecific cross-reacting antigen and biliary glycoprotein antigen, was present in all TCV but was not present in UPTC. COL-1, a CEA-specific monoclonal antibody, was nonimmunoreactive with all TCV and UPTC cases. Epithelial membrane antigen (EMA) was present in all TCV but was also present focally in eight of 16 UPTC, sometimes in a membranous pattern in epithelium surrounding cystic or hemorrhagic spaces. Strong immunoreactivity with antibodies to Leu M1 and EMA in papillary carcinomas of the thyroid has been associated with advanced stages of disease and tumor-associated mortality. The pattern of immunoreactivity in TCV is dissimilar to that in UPTC and is supportive evidence that TCV is a neoplasm that is distinct from papillary thyroid carcinoma of the usual type.

Leu-7 immunoreactivity in cytologic specimens of thyroid lesions, with emphasis on follicular neoplasms.

Anti-Leu-7 (HNK-1, CD 57) antibody, a marker for natural killer lymphocytes, was employed by Ghali et al. (Hum Pathol 1992;23: 21-25) to study surgically resected formalin-fixed, paraffin-embedded thyroid lesions. They demonstrated strong immunoreactivity of this antibody with thyroid carcinomas, both follicular and papillary, and only occasional weak immunoreactivity with colloid goiters and follicular adenomas. We studied cytologic specimens (primarily fine-needle aspiration biopsy specimens) from 44 thyroid lesions, including 10 follicular carcinomas, 14 follicular adenomas, seven adenomatous nodules, six papillary carcinomas, and seven cases of Hashimoto's thyroiditis. All follicular carcinomas exhibited immunoreactivity to anti-Leu-7 antibody, usually of a moderate to strong degree (9/10); however, six of 14 follicular adenomas yielded similar results. The patterns of immunoreactivity in the other lesions were similar to those previously described (Ghali et al., Hum Pathol 1992;23:21-25). It does not appear that anti-Leu-7 antibody can be used as a specific marker of malignancy in the cytologic assessment of follicular neoplasms of the thyroid.

Quantitative image analysis of MIB-1 immunoreactivity. A comparison with flow cytometric assessment of proliferative activity in invasive carcinoma of the breast.

Proliferative activity, especially flow cytometrically determined S-phase fraction, is generally accepted as an important prognostic indicator in carcinoma of the breast. We studied cellular proliferation in 53 breast carcinomas using quantitative image analysis of immunoreactivity to a recently available monoclonal antibody, MIB-1, which is applicable to formalin-fixed, paraffin-embedded tissues. MIB-1 is a murine monoclonal antibody that reacts with the Ki-67 nuclear antigen expressed by proliferating cells in the late G1, and G2/M phases of the cell cycle. These results were compared to flow cytometric determinations of S-phase and S + G2/M phase fractions obtained from corresponding fresh tissue samples. There was a good correlation between quantitative immunoreactivity to MIB-1 as measured by image analysis and flow cytometric S-phase and S + G2/M phase fractions (r = .63, P < .00001; r = .607, P < .00001, respectively). Immunoreactivity to MIB-1 and flow cytometric S-phase and S + G2/M phase fractions were significantly increased in aneuploid tumors as compared to diploid tumors. Histologic grade correlated with flow cytometric S-phase and S + G2/M phase fractions and MIB-1 immunoreactivity as determined by image analysis. There was a correlation between tumor size and MIB immunoreactivity. No proliferative parameters significantly correlated with lymph node status. Assessment of proliferative activity by quantitative image analysis of immunoreactivity to monoclonal MIB-1 antibody may be employed in cases of invasive carcinoma of the breast in which flow cytometric analysis fails to result in quantitative proliferative values, or it may be used as an alternative measurement of such proliferative activity.

Tamm-Horsfall protein in bladder tissue. Morphologic spectrum and clinical significance.

Tamm-Horsfall protein (THP) is a high-molecular-weight glycoprotein synthesized exclusively by the ascending loop of Henle and the distal tubule of normal kidney. In pathologic conditions, THP may accumulate in renal parenchyma, perirenal soft tissue, or renal hilar lymph nodes. Our recent finding of a cystectomy specimen showing large mural deposits of THP prompted a pertinent literature search, which uncovered only a single article in which THP deposition in bladder is briefly mentioned. In the current study, the clinical and morphologic features of THP were studied in 247 consecutive bladder biopsies and 15 cystectomies obtained in a 1-year period. A total of 18 cases were found (an incidence of 6.9%), with cystectomy specimens being much more frequently affected than biopsy specimens (60 versus 3.6%). Most patients were elderly men (45-78 years, with a mean 61 years; a male/female ratio of 16:2). In seven cases, THP appeared as large, "waxy," pale or weakly eosinophilic masses, so characteristic that the diagnosis could be readily made without any special studies. THP in these cases was strongly positive by periodic acid-Schiff, pale blue on Masson's trichrome stain, and ultrastructurally composed of nonbranching 4-nm-wide fibrils arranged in a parallel fashion. In 11 cases, THP appeared as inconspicuous flecks or interconnecting strands of eosinophilic material obscured by a large amount of adjacent fibrinous exudate or necrotic tissue. In these cases, the PAS and trichrome stains were not always helpful in the diagnosis. Immunostaining using an anti-THP antibody clearly identified even small amounts of THP in all 18 cases. This immunostaining was not only sensitive but also specific, giving a negative result for 64 control cases containing such materials as amyloid, fibrin, dense fibrosis, tissue necrosis, and edema fluid, all of which can potentially simulate THP. Although diagnoses for the specimens with THP were variable (nine transitional cell carcinomas, one squamous cell carcinoma, two nephrogenic adenomas, and five cases of cystitis), the areas where THP was deposited in each of these cases invariably showed necrosis, inflammation, fibrinous exudate, ulcer, or crystalline material. The mechanism for THP precipitation is not clear but is probably related to the mucosal changes, including inflammation and necrosis, which is always seen in areas of THP deposition. Follow-up study did not show any bladder abnormalities pertinent to THP deposition. In summary, THP is frequently seen in bladder tissue and most probably represents an incidental finding of morphologic interest but of no clinical significance.

Clear cell epithelial-myoepithelial carcinoma arising in pleomorphic adenoma of the lacrimal gland.

BACKGROUND: A 63-year-old man had an 8-year history of painless proptosis, which had noticeably increased over the last 2 months. A mass was palpable in the left lateral canthus. Computed tomographic studies showed a globular mass with small foci of calcification involving the lacrimal gland. After an incisional biopsy, a histologic diagnosis of clear cell epithelial-myoepithelial carcinoma was made and an orbital exenteration was performed. FINDINGS: Results of histologic examination of the mass showed a partially encapsulated, clear cell epithelial-myoepithelial carcinoma with an associated pleomorphic adenoma (benign mixed tumor). Immunohistochemical studies disclosed strong immunoreactivity to cytokeratin (AE1/AE3), epithelial membrane antigen, S-100 protein, and alpha-actin. CONCLUSION: Although a clear cell myoepithelial carcinoma rarely has been reported in association with a pleomorphic adenoma of the submandibular gland, to the authors' knowledge, this combination has never been reported in the lacrimal gland, nor has a clear cell epithelial-myoepithelial carcinoma ever been reported in this anatomic location. The differential diagnosis of lesions with prominent clear cells involving the lacrimal gland is extensive and includes clear cell variants of acinic cell carcinoma and oncocytoma, mucoepidermoid carcinoma, and others.