Inhibition of the phosphoinositide 3-kinase pathway for the treatment of patients with metastatic metaplastic breast cancer.

BACKGROUND: Mesenchymal/metaplastic breast cancers (MpBCs) are often triple-negative (TNBC), and chemo-refractory, and can harbor phosphoinositide 3-kinase (PI3kinase) alterations; thus, therapy with mTor inhibitors may demonstrate activity. PATIENTS AND METHODS: Patients with mesenchymal/MpBC treated with temsirolimus-based regimens were evaluated. Mutational analyses [polymerase chain reaction (PCR)-based DNA sequencing method, mass spectrometric detection (Sequenom MassARRAY), or next-generation sequencing] as well as loss of phosphatase and tensin homolog (PTEN) (immunohistochemistry) were performed (archived tissue when available). RESULTS: Twenty-three patients (one of whom was on two separate trials) were treated using temsirolimus-containing regimens: temsirolimus alone (n = 1 patient) or combined with the following: liposomal doxorubicin and bevacizumab (DAT, n = 18); liposomal doxorubicin (DT, n = 1); paclitaxel and bevacizumab (TAT, n = 2); paclitaxel (TT, n = 1); carboplatin and bevacizumab (CAT, n = 1). Response rate [complete response (CR) + partial response (PR)] was 25% across all regimens; 32% in the anthracycline-based regimens [DAT and DT (CR = 2, PR = 4; N = 19)]. An additional two patients achieved stable disease (SD) ≥6 months [total SD ≥6 months/CR/PR = 8 (33%)]. Molecular aberrations in the PI3K pathway were common: PIK3CA mutation = 6/15 (40%), PTEN mutation = 3/11 (27%), and PTEN loss = 2/11 (18%). A point mutation in the NF2 gene (K159fs*16; NF2 alterations can activate mTor) was found in one patient who attained CR (3+ years). Of the eight patients who achieved SD ≥6 months/CR/PR, all 4 patients with available tissue had a molecular aberration that activate the PIK3CA/Akt/mTOR axis: PIK3CA mutation = 2; PTEN loss = 1; NF2 aberration = 1. CONCLUSIONS: DAT has activity in MpBCs including complete CRs. Molecular aberrations that can activate the PI3 K/Akt/mTOR axis are common in MpBC.

Metaplastic sarcomatoid carcinoma of the breast appears more aggressive than other triple receptor-negative breast cancers.

Metaplastic sarcomatoid carcinoma (MSC) of the breast is usually triple receptor (ER, PR, and HER2) negative and is not currently recognized as being more aggressive than other triple receptor-negative breast cancers. We reviewed archival tissue sections from surgical resection specimens of 47 patients with MSC of the breast and evaluated the association between various clinicopathologic features and patient survival. We also evaluated the clinical outcome of MSC patients compared to a control group of patients with triple receptor-negative invasive breast carcinoma matched for patient age, clinical stage, tumor grade, treatment with chemotherapy, and treatment with radiation therapy. Factors independently associated with decreased disease-free survival among patients with stage I-III MSC of the breast were patient age > 50 years (P = 0.029) and the presence of nodal macrometastases (P = 0.003). In early-stage (stage I-II) MSC, decreased disease-free survival was observed for patients with a sarcomatoid component comprising ≥ 95% of the tumor (P = 0.032), but tumor size was the only independent adverse prognostic factor in early-stage patients (P = 0.043). Compared to a control group of triple receptor-negative patients, patients with stage I-III MSC had decreased disease-free survival (two-sided log rank, P = 0.018). Five-year disease-free survival was 44 ± 8% versus 74 ± 7% for patients with MSC versus triple receptor-negative breast cancer, respectively. We conclude that MSC of the breast appears more aggressive than other triple receptor-negative breast cancers.

Loss of myoepithelium is variable in solid papillary carcinoma of the breast.

AIMS: Reports on the frequency of myoepithelial loss in solid papillary carcinoma (SPC) of the breast, an unusual variant of papillary carcinoma with a solid pattern of expansile growth, have been strikingly contradictory. The aim was to clarify the frequency of myoepithelial loss in cases of SPC diagnosed at our institution. METHODS AND RESULTS: Eleven cases of SPC with available blocks or unstained slides were retrieved from the M. D. Anderson archives or obtained from outside contributors. Immunohistochemistry for smooth muscle actin (SMA) and p63 was evaluated on the circumscribed nests that appeared to be non-invasive by haematoxylin and eosin morphology. Three of the 11 cases (27%) were positive for both SMA and p63 at the periphery of all such foci, whereas eight cases (73%) lacked staining for both myoepithelial markers in at least one focus. Of these eight cases, one was diagnosed with only microinvasion, yet metastatic tumour resembling the circumscribed primary SPC was identified in two ipsilateral axillary lymph nodes. CONCLUSIONS: SPC of the breast frequently lacks myoepithelial markers at the tumour-stromal interface in spite of a circumscribed non-invasive appearance. Metastases from such tumours are infrequent, but can occur in cases that lack myoepithelial marker expression by immunohistochemistry.

Aberrant methylation and simian virus 40 tag sequences in malignant mesothelioma.

Aberrant promoter methylation and resultant silencing of several genes plays an important role in the pathogenesis of many tumor types. We compared the methylation profile of 66 malignant mesotheliomas (MMs) and 40 lung adenocarcinomas using methylation-specific PCR for seven genes frequently methylated in lung cancer. We also compared the methylation frequencies of these genes as well as the methylation index, a reflection of all of the gene frequencies, with the presence of SV40 large T-antigen (Tag) sequences, histological subtype, and patient survival. Our major findings are: (a) with the exception of the RASSF1A promoter of the RASSF1 gene, frequencies of aberrant methylation were significantly lower in MMs than in adenocarcinomas; (b) the frequency of RASSF1A aberrant methylation and the value of the methylation index were significantly higher in SV40 sequence positive MM than in negative MM; and (c) the methylation index was higher in epithelial MM than in sarcomatous/mixed MM. Our results demonstrate a relationship between SV40 and aberrant methylation in MMs.

Aberrant methylation of the adenomatous polyposis coli (APC) gene promoter 1A in breast and lung carcinomas.

The adenomatous polyposis coli (APC) gene is a tumor suppressor gene associated with both familial and sporadic cancer. Despite high rates of allelic loss in lung and breast cancers, point mutations of the APC gene are infrequent in these cancer types. Aberrant methylation of the APC promoter 1A occurs in some colorectal and gastric malignancies, and we investigated whether the same mechanism occurs in lung and breast cancers. The methylation status of the APC gene promoter 1A was analyzed in 77 breast, 50 small cell (SCLC), and 106 non-small cell (NSCLC) lung cancer tumors and cell lines and in 68 nonmalignant tissues by methylation-specific PCR. Expression of the APC promoter 1A transcript was examined in a subset of cell lines by reverse transcription-PCR, and loss of heterozygosity at the gene locus was analyzed by the use of 12 microsatellite and polymorphic markers. Statistical tests were two-sided. Promoter 1A was methylated in 34 of 77 breast cancer tumors and cell lines (44%), in 56 of 106 NSCLC tumors and cell lines (53%), in 13 of 50 SCLC cell lines (26%), and in 3 of 68 nonmalignant samples (4%). Most cell lines tested contained the unmethylated or methylated form exclusively. In 27 cell lines tested, there was complete concordance between promoter methylation and silencing of its transcript. Demethylation with 5-aza-2'-deoxycytidine treatment restored transcript 1A expression in all eight methylated cell lines tested. Loss of heterozygosity at the APC locus was observed in 85% of SCLCs, 83% of NSCLCs, and 63% of breast cancer cell lines. The frequency of methylation in breast cancers increased with tumor stage and size. In summary, aberrant methylation of the 1A promoter of the APC gene and loss of its specific transcript is frequently present in breast and NSCLC cancers and cell lines and, to a lesser extent, in SCLC cell lines. Our findings may be of biological and clinical importance.

Loss of expression and aberrant methylation of the CDH13 (H-cadherin) gene in breast and lung carcinomas.

Expression of some members of the cadherin family is reduced in several human tumors, and CDH13 (H-cadherin), located on chromosome 16q24.2-3, may function as a tumor suppressor gene. In human tumors, loss of expression of many tumor suppressor genes occurs by aberrant promoter region methylation. We examined the methylation status of the CDH13 promoter in breast and lung cancers and correlated it with mRNA expression using methylation-specific PCR and reverse transcription-PCR. Methylation was frequent in primary breast tumors (18 of 55, 33%) and cell lines (7 of 20, 35%). In lung cancers, methylation was present more frequently in non-small cell lung cancer tumors (18 of 42, 43%) and cell lines (15 of 30, 50%) than in small cell lung cancer cell lines (6 of 30, 20%; P = 0.03). Only the methylated or unmethylated forms of the gene were present in most (73 of 80, 91%) tumor cell lines. CDH13 expression was present in 24 of 30 (80%) of nonmethylated tumor lines. All 18 methylated lines tested lacked expression irrespective of whether the unmethylated form was present, confirming biallelic inactivation in methylated lines. Gene expression was restored in all five methylated cell lines tested after treatment with the demethylating agent 5'-aza-2-deoxycytidine. Our results demonstrate frequent aberrant methylation of CDH13 in breast and lung cancers accompanied by loss of gene expression, although expression may occasionally be lost by other mechanisms.

Expression of protease-activated receptor 1 in oral squamous cell carcinoma.

Protease-activated receptor 1 (PAR-1) is a G-coupled membrane protein. In this study, we analyzed the expression of PAR-1 in oral squamous cell carcinomas (SCCs). PAR-1 was expressed in oral SCCs, but the level of PAR-1 protein was lower in non-metastatic cells than in metastatic cells. Thrombin stimulated the growth of metastatic cells, and both thrombin and thrombin receptor activation peptide (TRP) enhanced the adhesion of these cells to fibronectin, but had no effect on non-metastatic cells. Thrombin and TRP also induced matrix metalloproteinase (MMP)-2 and MMP-9 activities in metastatic cells. These results suggest that PAR-1 may contribute to the growth and invasive potential of oral SCC.

DNA methylation profiles of lung tumors.

Aberrant methylation of CpG islands in promoter regions of tumor cells is one of the major mechanisms for silencing of tumor suppressor genes. We determined the frequency of aberrant promoter methylation of the p16, adenomatous polyposis coli (APC), H-cadherin (CDH13), glutathione S-transferase P1 (GSTP1), O6-methylguanine-DNA-methyltransferase (MGMT), retinoic acid receptor beta-2 (RAR beta), E-cadherin (CDH1), and RAS association domain family 1A (RASSF1A) genes in 198 tumors consisting of small cell lung cancers [SCLCs (n = 43)], non-small cell lung cancers [NSCLCs (n = 115)], and bronchial carcinoids (n = 40). The profile of methylated genes in the two neuroendocrine tumors (SCLC and carcinoids) were very different from that of NSCLC. However, whereas the overall pattern of aberrant methylation of carcinoids was similar to that of SCLC, carcinoids had lower frequencies of methylation for some of the genes tested. There were also significant differences in the methylation profiles between the two major types of NSCLC, adenocarcinoma and squamous cell carcinoma. We performed cluster analysis and found that SCLCs clustered with other SCLCs and carcinoids but not with NSCLCs, whereas the NSCLCs tended to cluster together. Within NSCLCs, adenocarcinomas and squamous cell carcinomas clustered with their respective histological types. Finally, we compared the methylation profiles of SCLC and NSCLC tumors and their respective cell lines (n = 44). In general, methylation frequencies were higher in tumor cell lines, but these differences were seldom significant. Thus, tumor cell lines appear to be suitable models to study aberrant DNA methylation. We conclude that SCLC, carcinoids, squamous cell carcinomas, and adenocarcinomas of the lung have unique profiles of aberrant methylation. Our findings should help us understand differences in the pathogenetic mechanisms of lung cancers.

Adhesion of aspirated tumor cells to extracellular matrix proteins: a new methodology utilizing fine-needle aspiration.

BACKGROUND: Cell adhesion molecules mediate the interactions of cells with other cells and with extracellular matrix components. Such interactions may be important in the development of tumor invasion and metastasis. This article describes a new approach to the evaluation of tumor cell-matrix interactions by utilizing fine-needle aspiration of resected tumors. METHODS: Fine-needle aspiration was performed on 15 fresh surgical specimens of various types of carcinomas. After partial purification by isotonic Percoll centrifugation, tumor cell adhesion to collagen Type IV, laminin, and fibronectin was evaluated by counting cytologically malignant cells adhering to matrix-coated plastic substrates. Frozen tissue sections of the corresponding tumors were studied simultaneously for immunohistochemical expression of alpha-2, alpha-3, alpha-4, and alpha-5 integrin subunit expression. Results of the immunohistochemical staining then were compared with the adhesion data for particular tumors. RESULTS: In general, the majority of the tumors exhibited little or no adhesion to collagen or laminin, but several tumors showed marked adhesion to fibronectin. Striking differences were noted between some tumors of the same histologic subtype. Competitive inhibition studies performed with two of the tumors (a large cell carcinoma and a renal cell carcinoma) showed decreased adhesion to fibronectin in the presence of anti-alpha-5, suggesting at least a partial role for the alpha-5-beta 1 fibronectin receptor in mediating the adhesion of these tumors to fibronectin. All the tumors examined exhibited strong immunohistochemical expression of the alpha-2 and alpha-3 integrin subunits, and all were negative for alpha-4. Three of the tumors showed weak expression of alpha-5, two of which (a squamous cell carcinoma and a renal cell carcinoma) were the tumors that showed the greatest adhesion to fibronectin. CONCLUSIONS: Quantitative adhesion data can be obtained using cell suspensions prepared from fine-needle aspirates, and there are marked differences in adhesive properties between particular tumors. Although two of the tumors showed a correlation between adhesion to fibronectin and immunohistochemical expression of the alpha-5 integrin subunit, matrix adhesion does not necessarily correlate with immunohistochemical expression of adhesion molecule receptors. In the future, this methodology potentially could be of value in determining which patients may benefit from therapies aimed at modifying tumor cell-matrix interactions.

Extra-articular synovial chondromatosis of the temporomandibular joint: pitfalls in diagnosis.

Synovial chondromatosis is a benign disease that only rarely affects the temporomandibular joint. When it does, disease is usually confined to the joint space itself but can occasionally extend beyond the joint capsule into the parotid gland, temporal bone, or cranium. The local clinical behavior, radiographic appearance, and histopathologic features can combine to create the appearance of a malignant lesion. We report a case of synovial chondromatosis that affected the temporomandibular joint and presented as an external auditory canal mass. The lesion was thought to be a chondrosarcoma prior to the definitive resection. Pitfalls in the diagnosis and management of synovial chondromatosis are discussed.

Correlation of CD44S expression in renal clear cell carcinomas with subsequent tumor progression or recurrence.

BACKGROUND: Recent reports have shown altered expression of CD44 in renal cell carcinomas. However, to the authors' knowledge there are no data correlating CD44 expression in renal cell carcinomas with subsequent tumor progression or recurrence, nor is there information about the presence of particular splice variants of CD44 in these tumors. METHODS: The authors examined the immunohistochemical expression of CD44S, the standard isoform of CD44, in renal cell carcinomas from 43 patients using 2 different monoclonal antibodies, Mab2137 and Hermes-3. In addition, they stained the renal cell carcinomas with antibodies to 2 splice variants of CD44, CD44v3 and CD44v6. RESULTS: Increased staining of renal clear cell carcinomas with Mab2137 was observed in high grade versus low grade tumors (45% vs. 0%, P = 0.013), whereas increased staining of clear cell carcinomas with Hermes-3 was noted in high stage versus low stage tumors (40% vs. 0%, P = 0.006). Few tumors stained with antibodies to CD44v3. Although increased expression of the splice variant CD44v6 was noted in papillary versus clear cell carcinomas, and increased staining of papillary carcinomas with Mab2137 and with antibodies to CD44v6 was noted for low stage versus high stage tumors, these differences did not achieve statistical significance. Clinical follow-up of at least 43 months was available for 26 patients. Six of these patients (five with clear cell carcinoma and one with papillary carcinoma) developed progressive or recurrent disease. The primary tumors from all 5 patients with progressive or recurrent clear cell carcinoma showed staining with Mab2137, whereas the primary tumors from only 2 of the 15 patients with at least 43 months follow-up and no evidence of progressive or recurrent clear cell carcinoma (13%) showed staining with Mab2137 (P = 0.001). Alternatively, 5 of 7 clear cell carcinomas (71%) that stained with Mab2137 were from patients who subsequently developed recurrence or progression, compared with 0 of 13 clear cell carcinomas that did not stain. Similar findings were not observed for papillary carcinomas, which appeared to be biologically distinct from clear cell carcinomas. CONCLUSIONS: CD44S staining with Mab2137 correlates with progression or recurrence of clear cell renal cell carcinoma. CD44S may, therefore, play a pathogenetic role in tumor progression.

Intrasellar adenoid cystic carcinoma and papillary mucinous adenocarcinoma: two previously undescribed primary neoplasms at this site.

Most carcinomas involving the sella turcica are metastases. We report two previously undescribed carcinomas that appear to be primary at this site. The first occurred in a 44-year-old woman who presented with hemianopsia. A mass was noted by computed tomography to occupy the sella turcica, from which it appeared to originate. Transphenoidal biopsy showed the tumor to be an adenoid cystic carcinoma with a typical cribriform pattern. The patient died shortly after a subsequent attempt at tumor resection. The second tumor arose in a 55-year-old man who presented with diplopia. Computed tomography showed a mass in the sella turcica that was presumed to be a pituitary adenoma. However, transphenoidal resection revealed a mucinous adenocarcinoma composed of small papillae and glands lined by columnar epithelium. The tumor cells exhibited varying degrees of stratification with prominent interspersed mucin vacuoles. Focal solid areas showed a component of signet ring-type cells. In contrast to the apparent aggressive behavior of the adenoid cystic carcinoma, the papillary mucinous adenocarcinoma appeared much less aggressive, as the second patient was alive and without evidence of disease 5 years later. Both tumors may be derived from epithelial rests within the pituitary gland, either minor salivary gland rests or Rathke's cleft remnants.

Glomus tumor of the uterine cervix.

Two examples of glomus tumors of the cervix that were incidental findings in patients with uterine leiomyomas are described. The first occurred in a 52-year-old woman with two small uterine leiomyomas and an endometrial polyp. The second occurred in a 39-year-old woman with a large uterine leiomyoma. The glomus tumors were located deep in the cervical stroma and were 0.8 and 0.4 cm in maximal dimension, respectively. The tumors were composed of nests or trabeculae of small cells with round or ovoid hyperchromatic nuclei and eosinophilic or clear cytoplasm. The cells closely surrounded slitlike capillaries and were immunoreactive for smooth muscle actin and muscle specific actin. To our knowledge, no similar tumors have been reported in the cervix.

Fine needle aspiration of signet-ring cell lymphoma. A case report with differential diagnostic considerations.

BACKGROUND: Signet-ring cell lymphoma is an unusual morphologic variant of non-Hodgkin's lymphoma that, although well described histologically, is scarcely mentioned in the cytology literature. Its main significance lies in its potential for diagnostic confusion with more common lesions containing signet-ring cells. CASE: A 50-year-old, white male presented with a two-month history of persistent cervical lymphadenopathy and fatigue. Fine needle aspiration of a 2-cm, left, submandibular lymph node revealed classic signet-ring cells among small and large lymphoid cells. Also noted were multivacuolated cells. The background of the smears showed many vacuolated structures analogous to the lymphoglandular bodies seen in lymphoid proliferations without signet-ring cells. CONCLUSION: The differential diagnosis of signet-ring cell lesions by fine needle aspiration includes signet-ring cell lymphoma, sinus histiocytosis and metastatic adenocarcinoma, liposarcoma and melanoma. When confronted with such an aspirate, additional material should be obtained for immunocytochemical or flow cytometric analysis.

Salivary duct carcinoma. Is a specific diagnosis possible by fine needle aspiration cytology?

OBJECTIVE: To review the cytomorphologic features of salivary duct carcinoma and to evaluate the likelihood of definitive diagnosis by fine needle aspiration. STUDY DESIGN: The cytomorphologic features of two cases of salivary duct carcinoma, both occurring in the parotid gland in men over 80 years of age, were evaluated by fine needle aspiration and compared to cytologic features described in the literature. Additionally, previously reported diagnoses rendered by fine needle aspiration of salivary duct carcinomas were compiled from the cytology literature. The likelihood of arriving at a definitive diagnosis by fine needle aspiration was determined from the frequency of correct cytologic diagnoses reported in the literature. RESULTS: The most characteristic features of salivary duct carcinoma by fine needle aspiration appear to be flat sheets with a cribriform pattern and tumor cells in a necrotic background with pleomorphic, eccentric nuclei and granular cytoplasm. However, no definitive diagnoses of salivary duct carcinoma by fine needle aspiration have been recorded in the cytology literature. CONCLUSION: Because of the morphologic spectrum displayed by this tumor and the absence of definitive cytologic diagnoses in the literature to date, it is unclear whether a diagnosis of salivary duct carcinoma can be rendered by fine needle aspiration. Nevertheless, if cribriform groups are noted in a salivary gland aspirate, the diagnosis of salivary duct carcinoma should at least be considered.

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.

Testicular Sertoli cell tumor with a heterologous sarcomatous component: immunohistochemical assessment of Sertoli cell differentiation.

OBJECTIVE: Immunohistochemical staining is reported to be useful in distinguishing ovarian Sertoli-stromal cell tumors from carcinosarcomas. To assess Sertoli cell differentiation in a rare malignant biphasic testicular tumor, we compared the immunophenotypic profile of the tumor with that of Sertoli cell nodules and adenomas and mullerian carcinosarcomas. DESIGN: Immunohistochemical staining was performed on 6 testes (4 with hyperplastic Sertoli cell nodules, 2 with Sertoli cell adenomas) and 7 carcinosarcomas (6 involving the uterus, 1 involving the uterus and ovary) using primary monoclonal antibodies AE1/AE3, CAM 5.2, CA 19.9, and antibodies directed against epithelial membrane antigen, carcinoembryonic antigen (monoclonal and polyclonal), S100, placental alkaline phosphatase, and inhibin. These staining results were compared with those of the index case. RESULTS: All testes showed positive staining for inhibin and vimentin in the Sertoli cells of the nodules and adenomas. One Sertoli cell nodule showed focal staining with AE1/AE3 and CAM 5.2. Both adenomas showed focal positive staining for S100. All nodules and adenomas were negative for epithelial membrane antigen, monoclonal and polyclonal carcinoembryonic antigen, CA 19.9, and placental alkaline phosphatase. In contrast, the carcinomatous areas of the carcinosarcomas were all negative for inhibin but exhibited positive staining for AE1/AE3, CAM 5.2, and epithelial membrane antigen. The carcinosarcomas showed variable expression of vimentin, S100, carcinoembryonic antigen, CA 19.9, and placental alkaline phosphatase. The epithelial component of the tumor from the index case showed strong diffuse staining for inhibin and vimentin and only very faint focal staining with AE1/AE3 and CAM 5.2. The epithelial component was negative for epithelial membrane antigen, monoclonal and polyclonal carcinoembryonic antigen, S100, CA 19.9, and placental alkaline phosphatase. CONCLUSIONS: The immunohistochemical findings in the index case support the diagnosis of Sertoli cell tumor with a heterologous sarcomatous component over carcinosarcoma. Inhibin seems to be the best single marker for Sertoli cell differentiation. To our knowledge, only 1 other case of this rare testicular tumor has been reported in the literature.

Fine-needle aspiration of basaloid squamous carcinoma: a case report with review of differential diagnostic considerations.

Basaloid squamous carcinoma is a distinct variant of squamous carcinoma with a particularly poor prognosis. To our knowledge, there are only two papers in the cytopathology literature which describe this entity. We report the fine-needle aspiration findings of an additional case of metastatic basaloid squamous carcinoma in a cervical lymph node and compare its cytomorphologic features to those observed on touch imprints of the subsequent surgical specimen. Smears of the aspirate showed a mixed lymphoid background with interspersed cohesive clusters of small cells roughly 3 times the size of small mature lymphocytes. Some cells were angulated and others exhibited irregular nuclear contours. The cells were generally hyperchromatic with evenly staining dense chromatin or irregularly distributed coarse chromatin. Focally there was evidence of nuclear molding. On Diff-Quik staining, irregular globules of magenta-stained extracellular dense material were noted within or adherent to the periphery of some clusters or as somewhat linear formations with small epithelial cells clinging to the edges. Abundant mitotic figures and clumps of necrotic tumor were more apparent on touch preps of the subsequent surgical specimen. The differential diagnosis by fine-needle aspiration includes adenoid cystic carcinoma, basal-cell adenocarcinoma, adenosquamous carcinoma, and small-cell carcinoma. If a fine-needle aspirate of a cervical lymph node shows the features described above and the primary tumor is unknown, suggesting the possibility of metastatic basaloid squamous carcinoma may aid clinicians in the search for a primary site, as basaloid squamous carcinoma occurs most frequently at the base of the tongue, hypopharynx, and supraglottic larynx.

Tyrosine-rich crystals associated with oncocytic salivary gland neoplasms.

OBJECTIVE: Crystalloids have been identified ultrastructurally within the epithelial cells of Warthin's tumors, but there have been no studies characterizing crystals or crystalloids in Warthin's tumors by light microscopy. The finding of abundant needle-shaped crystals in a fine-needle aspirate of a cystadenoma of the parotid prompted us to examine the prevalence of crystals and crystalloids in oncocytic salivary gland neoplasms. DESIGN: Ninety-seven oncocytic neoplasms (93 Warthin's tumors, 3 cystadenomas, and 1 oncocytoma) excised at our institution between 1950 and 1996 were examined, to identify crystals. Neoplasms with crystals were further characterized by means of a variety of histochemical stains and electron microscopy. Ninety-nine pleomorphic adenomas were similarly reviewed. RESULTS: Seven cases with crystals were identified. Five of these were Warthin's tumors, 1 was a cystadenoma, and 1 was an oncocytoma. The crystals were noted within tumor cysts but were not limited to the neoplasms. The crystals were predominantly either needle-shaped or tabular, but some cases contained mixtures of both as well as intermediate forms. They stained pink with hematoxylin-eosin, although the tabular forms also exhibited a focal yellow hue. The crystals were not discernible under polarized light. They stained a red-brown color with Millon's reagent, which indicated the presence of tyrosine. Trichrome, periodic acid-Schiff stain with diastase, alcian blue (pH 2.5), and Congo red stains were negative. Electron microscopy revealed sharply defined, elongate, electron-dense structures with periodicity, both extracellular and within epithelial cells. No crystals or crystalloids were identified in any of 99 pleomorphic adenomas reviewed. CONCLUSIONS: The findings indicate that tyrosine-rich crystals associated with several oncocytic salivary gland neoplasms are morphologically, histochemically, and ultrastructurally distinct from previously described tyrosine-rich crystalloids and collagenous crystalloids of pleomorphic adenomas. Although the crystals appear to form by the assembly of small units within epithelial cells, the exact mode of formation remains unclear.