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Objectives: Wegener's granulomatosis is a granulomatous and necrotizing vasculitis that classically involves the respiratory and renal systems. The goal of the study was to define clinical and pathological characteristics in a subgroup of patients with the changes of Wegener's granulomatosis involving the orbit. Study Design: Retrospective study. Methods: A database search identified 15 patients with the histological changes of Wegener's granulomatosis of the orbit presenting over a 23-year period. A review of the histological specimens, radiological studies, and patient charts was performed. Additional follow-up data were obtained through patient interviews. Results: Of 15 patients (median age, 54 y) with Wegener's granulomatosis of the orbit identified, the disease was limited to the orbit in 12 patients; 3 patients had additional sinonasal involvement. All patients underwent various surgical procedures followed by medical treatment (cyclophosphamide and prednisone). Specimens showed characteristic histopathological features of Wegener's granulomatosis. Follow-up data were available for 12 patients with a median period of 5 years. In the group with only orbital involvement, none of the patients developed systemic progression of Wegener's granulomatosis. Only one patient had multiple local recurrences and later developed contralateral orbital Wegener's granulomatosis. Conclusions: Wegener's granulomatosis limited to the orbit is a localized form of the disease without systemic progression. Diagnostic surgical procedures followed by aggressive medical treatment results in good outcome, although local recurrence may occur. [ABSTRACT FROM AUTHOR]

Aims: Extranodal NK/T cell lymphoma, nasal type (ENKTCL) is usually composed of medium- to large-sized lymphoid cells showing prominent angiotrophism and tumour cell necrosis. We report 13 cases composed predominantly of small lymphocytes diagnosed in the United States and Western Europe., Methods and Results: Patients included seven females and six males aged 17-75 years. Ten presented with sinonasal and three with buccal disease. Nine had stage IE/IIE and four had stage IV disease. In five of seven patients with multiple biopsies at different time-intervals, the lymphoma was misinterpreted as representing chronic inflammation on an earlier biopsy. In all cases morphology showed a dense infiltrate of small lymphoid cells with minimal cytological atypia. Necrosis, angioinvasion and angiodestruction were each seen in 17%, 22% and 17% of biopsies. Median Ki67 was 5%. Four patients died of lymphoma 4-16 months after diagnosis, including three of four patients with stage IV disease; seven (54%) are alive with no evidence of disease at a median of 39 months; one patient with stage IV disease is alive at 10 months and one recurred at 17 months., Conclusions: In sinonasal biopsies with predominantly small lymphocytic infiltrates with admixed chronic inflammation, focal hypercellularity, focal surface ulceration or microscopic bone invasion by small lymphoid cells should alert pathologists to the possibility of small-cell predominant ENKTCL. Awareness of the full histological spectrum of ENKTCL, particularly in non-endemic areas, is important in avoiding a delay in diagnosis and ensuring timely initiation of therapy., (© 2016 John Wiley & Sons Ltd.)

Background: Chronic sclerosing sialadenitis is a fibroinflammatory disease of the salivary glands, characteristically of the submandibular gland. One prior Asian study proposed that chronic sclerosing sialadenitis is a part of the spectrum of IgG4-associated disease. This association has not been confirmed in Western populations. We therefore, investigated the relationship between IgG4 and chronic sclerosing sialadenitis, and compared the histomorphologic features of this condition with those of chronic sialadenitis-not otherwise specified, Sjögren syndrome, and lymphoepithelial sialadenitis., Materials and Methods: We evaluated 13 cases of chronic sclerosing sialadenitis and compared them with 15 cases of chronic sialadenitis-not otherwise specified, 8 lip biopsies from individuals with Sjögren syndrome, and 4 cases of lymphoepithelial sialadenitis. Immunohistochemistry for IgG, and IgG4 was carried out. IgG4-positive plasma cells were quantified and the IgG4/IgG ratio was calculated., Results: Seven patients with chronic sclerosing sialadenitis were female and 6 were male. Their mean age was 61 years (range: 27 to 80). Twelve chronic sclerosing sialadenitis cases involved the submandibular gland (bilaterally in 3) and in 1 there was a parotid lesion. Three of these 12 cases had manifestations of IgG4-associated systemic disease. Morphologically these specimens had preservation of lobular architecture, hypercellular interlobular fibrosis, florid lymphoid hyperplasia, and numerous plasma cells. Obliterative phlebitis was observed in 6 cases. The histologic features of chronic sclerosing sialadenitis were reminiscent of autoimmune pancreatitis, and were either not observed or were present only focally in cases of chronic sialadenitis, Sjögren syndrome, and lymphoepithelial sialadenitis.Eleven of 12 evaluable cases showed an increased number of IgG4 plasma cells with a mean of 229/high-power field (HPF) (range 75 to 608) and an overall IgG4/IgG ratio of 0.86 (range 0.5 to 1). The only patient whose biopsy lacked IgG4-positive plasma cells had pathologic evidence of cytomegalovirus infection. Chronic sclerosing sialadenitis cases, in comparison with the other 3 groups studied, showed a significantly higher number of IgG4 positive plasma cells (P<0.05). Patients with chronic sialadenitis-not otherwise specified had a median number of only 16 IgG4-positive plasma cells/HPF (range 2 to 44), with an IgG4/IgG ratio of 0.14 (range 0.02 to 0.28). The Sjögren syndrome patients had a median of 1 IgG4-positive plasma cell/HPF (range 0 to 3), with an IgG4/IgG ratio of 0.02 (range 0 to 0.07). Patients with lymphoepithelial sialadenitis had a median of 0 IgG4-positive plasma cells per HPF., Conclusion: Chronic sclerosing sialadenitis has a characteristic morphologic appearance. This morphologic appearance, in conjunction with the elevated IgG4 expression, distinguishes chronic sclerosing sialadenitis from other inflammatory diseases of the salivary glands. Chronic sclerosing sialadenitis belongs to the spectrum of IgG4-related diseases.

The anatomy of the distal incus, including the lenticular process, was examined in histological sections from 270 normal cadaveric human temporal bones aged between less than 1 month and 100 years. All but nine of these sectioned specimens showed signs of a bony connection between the long process of the incus and the flattened plate of the lenticular process, and in 108 specimens a complete bony attachment was observed in a single 20 microm section. In these 108 ears, the bony lenticular process consisted of a proximal narrow "pedicle" connected to a distal flattened "plate" that forms the incudal component of the incudo-stapedial joint. A fibrous joint capsule extended from the stapes head to the pedicle of the lenticular process on all sides, where it was considerably thickened. Three-dimensional reconstructions made from serial 20 microm sections of four bones provided views from all directions that easily convey the anatomical features of this region. Morphometric measurements of the bony architecture of the distal incus in 103 temporal bones were made, including lengths and cross-sectional areas, estimates of the percentage of lacunae containing osteocytes, and the degree of bone resorption. These measurements, analyzed as a function of age, provided an anatomic description over a large age range that can serve as a normal baseline against which structural pathology can be compared. Although none of the bony dimensions showed significant age dependence, the estimated percentage of bony lacunae that contain osteocytes decreased significantly with age. The results have implications for the roles of specific components on the coupling of ossicular motion across the incudo-stapedial joint, and provide insights regarding bone resorption at the level of the distal incus, which occurs clinically in some patients with chronic otitis media or after stapedectomy.

Sclerosing polycystic adenosis (SPA) is a recently described, rare lesion of the salivary gland analogous to fibrocystic disease of the breast. Recognition of this benign entity is important since the differential diagnosis includes other more common benign and malignant salivary gland neoplasms, particularly mucoepidermoid carcinoma and tumors with cystic and oncocytic features. While the histomorphology of SPA is well documented, there is only one other cytologic description of SPA in the English-language literature. Here we describe the fine-needle aspiration biopsy findings in a case of SPA of the parotid gland in an 84-year-old woman. The aspirate was characterized by flat cohesive sheets of epithelial cells with moderate amounts of finely granular oncocytic cytoplasm and enlarged round nuclei with indistinct nucleoli. Some epithelial groups formed glandular structures with lumens, and the background contained small amounts of delicate mucoproteinaceous material. Occasional markedly vacuolated cells were present as well as many cells with apocrine change manifested by well-defined apical snouting. Familiarity with the cytomorphologic features of SPA, including its characteristic apocrine changes, is important for distinguishing it from other more clinically significant salivary gland lesions.

Endocrine mucin-producing sweat gland carcinoma (EMPSGC) is an underrecognized low-grade carcinoma with predilection to the eyelid. Only 4 cases of this entity have been described in the literature. Here, we describe 12 cases of EMPSGC. The lesions were twice as frequent in females than males with an average age of 70 years (range, 48-84 years). Clinically, they presented as a slowly growing cyst or swelling. The most common site of occurrence was the lower eyelid (8 cases). Two lesions occurred on the upper eyelid and 2 on the cheek. Histologically, they were well-circumscribed, typically multinodular tumors with solid or partially cystic nodules, frequently showing areas of papillary architecture. Focal cribriform arrangements were also present. The nodules were formed by uniform small- to medium-sized oval to polygonal epithelial cells with lightly eosinophilic to bluish cytoplasm. The nuclei were bland with diffusely stippled chromatin and inconspicuous nucleoli. Intracytoplasmic and extracellular mucin was usually present. Mitotic activity was present but never brisk. All tumors examined immunohistochemically expressed at least one neuroendocrine marker, synaptophysin or chromogranin. CD57 and neuron specific enolase, secondary markers of neuroendocrine differentiation, were expressed in most cases. All tumors tested expressed estrogen and progesterone receptors, cytokeratin 7, low molecular cytokeratin Cam5.2, and epithelial membrane antigen and were negative for cytokeratin 20 and S-100 protein. Calponin, smooth muscle actin, and p63 immunohistochemical stains did not disclose myoepithelial cells around larger tumor nests in most cases, supporting the notion that EMPSGC is an invasive carcinoma. In 10 cases, cystic areas lined by benign epithelium indistinguishable from eccrine ducts were present. In some foci, the benign ductal epithelium was undermined or replaced by carcinoma in situ with similar cytologic features to the solid or papillary areas of EMPSGC. Myoepithelial cells were preserved in the areas of in situ carcinoma. In 6 cases, EMPSGC was associated with invasive mucinous carcinoma. In situ carcinoma and mucinous carcinoma also expressed neuroendocrine markers. Clinical follow-up showed no recurrences or metastases, consistent with low-grade carcinoma. The series provides histologic evidence for a multistage progression of noninvasive sweat gland neuroendocrine carcinoma to EMPSGC and then to mucinous carcinoma of the eyelid. Although the data from this series support the notion that the prognosis of EMPSGC and mucinous carcinoma is good, longer follow-up is needed for better understanding of their pathogenesis and clinical behavior.

EBV infection is associated with virtually all cases of undifferentiated NPC, and the EBV-encoded LMP1 is expressed in a proportion of cases. LMP1 has transforming functions similar to members of the TNF receptor family and activates intracellular signaling cascades through interaction with TRAFs. In B cells, expression of TRAF1 is in turn upregulated by LMP1. LMP1 signaling in epithelial cells may be affected by the presence or absence of TRAF1. By immunohistochemistry, we detected TRAF1 expression in 17 of 42 (40%) EBV+ undifferentiated NPCs. All 7 LMP1+ NPC biopsies were also TRAF1+. Using an RNAse protection assay, high-level TRAF1 expression was detected in an LMP1-expressing NPC-derived cell line (C15) and expression was weaker in 2 LMP1- cell lines (C17, C19). Finally, LMP1 upregulated TRAF1 expression in an EBV- keratinocyte cell line. Our results demonstrate that TRAF1 is expressed in NPC tumor cells in vivo and suggest that TRAF1 expression may be upregulated by LMP1 in NPC. An antiapoptotic function has been proposed for TRAF1, and this may be relevant for the pathogenesis of NPC., (Copyright 2004 Wiley-Liss, Inc.)

Ligneous (pseudomembranous) inflammation of the female genital tract is a rare and unusual condition characterized by extensive subepithelial fibrin deposition and associated inflammation. Ligneous inflammation in extragenital sites, predominantly the conjunctiva, has been linked to plasminogen deficiency. Individuals with plasminogen deficiency are unable to remove fibrin deposited in injured mucosal tissue. Severe systemic ligneous inflammation involving the female genital tract that is linked to hypoplasminogenemia has not previously been described. We present a patient with ligneous inflammation of her genital, middle ear, and oral mucosa that was associated with type-1 homozygous plasminogen deficiency due to a novel missense mutation in the plasminogen gene.

The Epstein-Barr virus (EBV) is associated with virtually all cases of undifferentiated nasopharyngeal carcinoma (NPC) and has been classified as a group I carcinogen. In addition to its potential role in the pathogenesis of NPC, EBV also provides a possible target for immunotherapy of NPC, since a limited number of viral genes are expressed in the neoplastic cells. The EBV-encoded latent membrane protein 2A (LMP2A) is considered a promising target since it provides epitopes recognized by EBV-specific T-cells. Using immunohistochemistry, the present study shows that LMP2A is expressed at the protein level in the neoplastic cells of 16 of 35 (45.7%) NPC biopsies. This finding provides further evidence suggesting that NPC tumour cells may be susceptible to lysis by cytotoxic T-cells directed against LMP2A and should encourage efforts to develop immunotherapeutic approaches for the treatment of NPC., (Copyright 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.)

Adenoid cystic carcinoma is an indolent salivary gland malignancy that is associated with a poor long-term prognosis. The distinction of adenoid cystic carcinoma from other head and neck neoplasms can occasionally be problematic, particularly in small biopsies. Recent studies suggest that KIT (CD117) might be useful as an ancillary marker for adenoid cystic carcinoma; however, the expression of KIT in other benign and malignant head and neck neoplasms, including those that might mimic adenoid cystic carcinoma, has not been well studied. Here we use two different antibodies against KIT to evaluate its expression in a series of 66 adenoid cystic carcinomas compared with its expression in 98 other neoplasms of the head and neck. Overall, 94% (n = 62) of adenoid cystic carcinomas from various anatomic sites and of various histologic subtypes were positive for at least one of the KIT antibodies, and 77% (n = 50) of adenoid cystic carcinoma cases were positive for both antibodies. This contrasted with only 8% (n = 8) of other head and neck neoplasms that were positive for both KIT antibodies (P <.001). It was of note that certain neoplasms, including pleomorphic adenoma, basal cell adenoma, polymorphous low-grade adenocarcinoma, and basal cell carcinoma, that can show histologic overlap with adenoid cystic carcinoma had significantly less KIT immunoreactivity than did adenoid cystic carcinoma (P <.001). In contrast, KIT expression did not reliably distinguish adenoid cystic carcinoma from basal cell adenocarcinoma and basaloid squamous carcinoma (P >.05). The overall sensitivity of the two KIT antibodies for adenoid cystic carcinoma was 82-89%, and the specificity was 87-88%. The findings in this study support the potential use of KIT immunoexpression for distinguishing adenoid cystic carcinoma from many other benign and malignant head and neck neoplasms.

Although fine-needle aspiration biopsy (FNAB) is a highly accurate tool for the diagnosis of pleomorphic adenomas, even this common salivary gland neoplasm can be diagnostically challenging and cause pitfalls in cytodiagnosis. In particular, the presence of either cystic degeneration or squamous and mucinous metaplasia can lead to a false positive diagnosis of malignancy. Here we present the case of a 16-year-old female who presented with a painless, slowly growing mass in the superficial lobe of the right parotid gland. Magnetic resonance imaging of the parotid demonstrated a mass with heterogeneous postcontrast enhancement and a central, nonenhancing area suggestive of necrosis. FNAB of the lesion yielded proteinaceous debris and numerous whorls of keratin, small cohesive clusters of basaloid and squamoid epithelial cells, and many vacuolated and foamy cells. Initially and after consultation at an outside institution, the FNAB was reported as an "atypical neoplasm, cannot exclude mucoepidermoid carcinoma." A total, nerve-sparing parotidectomy and level II neck dissection revealed a pleomorphic adenoma with central cystic degeneration and extensive mixed appendageal differentiation. While foci of squamous metaplastic changes may occur in pleomorphic adenomas, the combination of cystic degeneration and extensive appendageal differentiation with numerous keratotic cysts is rare, and it presents the potential for misinterpretation of the FNAB as indicative of malignancy in general, and mucoepidermoid carcinoma in particular., (Copyright 2003 Wiley-Liss, Inc.)

We report a case of extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type of the salivary gland arising in a background of chronic sclerosing sialadenitis. Chronic sclerosing sialadenitis is a common fibrosing chronic inflammatory lesion of the submandibular gland, which is thought to be the result of sialolithiasis, and is not associated with a systemic autoimmune disease. Salivary MALT lymphomas are typically associated with lymphoepithelial sialadenitis (LESA) in a patient with or without Sjögren's syndrome. Our case of salivary MALT lymphoma was neither preceded by Sjögren's syndrome nor accompanied by LESA. This case suggests that chronic inflammatory processes other than Sjögren's syndrome may provide a substrate for the development of MALT lymphoma.

Background: Successful surgical management of primary hyperparathyroidism requires the ability to identify and distinguish normal from abnormal parathyroid tissue. Microscopic pathologic confirmation often helps with the diagnoses and decisions regarding the extent of parathyroid resection. Confocal reflectance microscopy (CRM) is an optical method of noninvasively imaging tissue without fixation, sectioning, and staining as in standard histopathology. The goal of this study was to determine if CRM imaging could be used to distinguish normal from diseased parathyroid tissue intraoperatively., Methods: In this study, 44 parathyroid glands from 21 patients undergoing operations for primary hyperparathyroidism were imaged immediately after excision. CRM images were compared with conventional hematoxylin-and-eosin stained sections obtained from the same gland. The percentage area occupied by fat cells was calculated in images of both normal and diseased glands., Results: Characteristic microscopic features of parathyroid glands were distinguishable by CRM and correlated well with histopathology. The stromal fat content of normal and diseased glands could easily be determined. The percentage area occupied by fat cells differed significantly (P <.00001) in normal glands (average, 23.0% +/- 10.9%) and adenomatous glands (average, 0.4% +/- 0.7%)., Conclusions: CRM imaging rapidly revealed microscopic features that reliably differentiated normal and diseased parathyroid glands. The success of this preliminary ex vivo study promotes interest in further development of an in situ probe for in vivo clinical diagnostic use.

Background: Papillary thyroid carcinoma is the most common malignant neoplasm of the thyroid gland, and fine-needle aspiration biopsy (FNAB) often is the initial diagnostic method used in its detection. Prior studies have shown that immunohistochemical staining for various cytokeratins in general, and cytokeratin 19 (CK19) in particular, can be applied as an ancillary technique for diagnosing papillary thyroid carcinoma in histologic specimens. In the current study the authors assessed the diagnostic utility of CK19 to detect papillary carcinoma effectively in cytologic preparations of thyroid FNABs., Methods: Immunocytochemical staining with CK19 was performed on cytologic aspirates from 37 papillary thyroid carcinomas and 36 other lesions of the thyroid (14 follicular adenomas, 10 multinodular goiters, 5 cases of Hashimoto thyroiditis, 6 oncocytic [Hürthle cell] neoplasms, and 1 follicular carcinoma). All cases included in the study had a corresponding histopathology specimen., Results: Positive immunocytochemical reactivity for CK19 was identified in 34 of 37 papillary carcinomas and in 1 of 36 other thyroid lesions (sensitivity of 92% and specificity of 97%). Although the strongest reactivity was obtained in methanol fixed thin layer preparations, the antibody also was effective in detecting papillary carcinoma in alcohol fixed and air-dried smears. The single false-positive case was a follicular adenoma with focal areas of papillary hyperplasia. All other aspirates including those from cases of Hashimoto thyroiditis, multinodular goiter, follicular adenoma, oncocytic neoplasms, and follicular carcinoma were negative., Conclusions: CK19 is an effective, highly sensitive, and specific ancillary tool for the diagnosis of papillary carcinoma in thyroid FNABs.

Purpose: This study attempted to identify differential cytokeratin expression in cystic jaw lesions using immunohistochemical staining., Patients and Methods: The charts from selected patients treated between 1983 and 1994 for jaw cysts were evaluated. Twenty-four paraffinized specimens were selected randomly for investigation with 5 immunohistochemical stains. The 4 diagnostic categories included ameloblastoma, dentigerous cyst, odontogenic keratocyst (OKC), and recurrent odontogenic keratocyst in patients with nevoid basal cell carcinoma (NBCC) syndrome. The 5 immunohistochemical stains included antibodies to cytokeratins 13, 17, and 18; CAM 5.2; AE 1/3; and carcinoembryonic antigen (CEA)., Results: Differential staining of OKCs from patients with and without NBCC syndrome was found only with the antibody to cytokeratin 17. Furthermore, staining of OKCs in syndromic patients appeared to be stronger and more uniform than in nonsyndromic patients., Conclusions: These findings suggest that immunohistochemical staining for cytokeratin 17 may aid in the diagnosis of OKCs and may be used to further subdivide these lesions based on the presence or absence of NBCC syndrome.

We present a case of dedifferentiated chondrosarcoma of the larynx in which the dedifferentiated component was initially diagnosed by fine-needle aspiration (FNA). The patient was a 74-yr-old man who presented with difficulty breathing and an anterior neck mass. A CT scan demonstrated a 4.5-cm cartilaginous lesion involving the left thyroid cartilage, with an anterior soft-tissue component. Nine years prior, the patient had an incomplete resection of a low-grade chondrosarcoma at the same site. FNA was performed on the current lesion, demonstrating a high-grade spindle-cell sarcoma with a storiform pattern. The cytomorphology together with immunocytochemistry and electron microscopy were diagnostic of malignant fibrous histiocytoma (MFH), and synthesis of the clinical, radiographic, and cytomorphologic features resulted in a diagnosis of dedifferentiated chondrosarcoma. The cytologic diagnosis was histologically confirmed by laryngectomy. Although rare, dedifferentiated chondrosarcoma should be included in the differential diagnosis of high-grade sarcomas of bone and cartilage assessed by FNA., (Copyright 2000 Wiley-Liss, Inc.)

Few large series compare lymphomas of the nasal cavity with those of the paranasal sinuses. We studied the cases of 58 patients, 34 males and 24 females, aged 7 to 92 years (mean, 57 years), who had lymphoma involving the nasal cavity or paranasal sinuses. Thirty-three patients had diffuse large B-cell lymphoma (DLBCL). Twenty-three were male and 10 were female, with an age range of 7 to 91 years (mean, 63 years); two were HIV-positive. Only 2 of 11 cases tested (one in an HIV-positive patient and one of lymphomatoid granulomatosis type) were Epstein-Barr virus (EBV)-positive. Thirty (91%) involved paranasal sinuses, 10 with nasal involvement, whereas three cases had nasal, but not sinus, involvement. At last follow-up, 16 (67%) were free of disease 7 to 169 months later (mean, 65 months), and 8 (33%) had died of disease 2 to 166 months later (mean, 45 months). Seventeen patients had nasal-type natural killer (NK)/T-cell lymphoma. There were 10 women and 7 men, aged 27 to 78 years (mean, 48 years). Thirteen of 14 were EBV-positive. Sixteen patients had nasal involvement, eight with sinus involvement. Eleven (73%) of 15 were alive and well 6 to 321 months later (mean, 139 months), three (20%) died of lymphoma 1, 11, and 12 months later, and one (7%) is alive with disease. There was one case each of marginal zone B-cell lymphoma, Burkitt's lymphoma, Burkitt-like lymphoma, peripheral T-cell lymphoma of unspecified type, and adult T-cell lymphoma/leukemia. In an additional three cases, the lymphomas were composed predominantly of large cells, but no immunophenotyping could be performed for subclassification. In 19 cases (17 DLBCLs, 1 Burkitt-like lymphoma, and 1 lymphoma of uncertain lineage), presenting symptoms included complaints related to the eyes. In 16 cases (13 DLBCLs, 1 Burkitt-like lymphoma, 1 nasal NK/T-cell lymphoma, and 1 lymphoma of uncertain lineage), the orbit was invaded by lymphoma. In our series, the most common lymphoma to arise in the sinonasal area is DLBCL, followed by nasal NK/T-cell lymphoma. Comparison of these two types of lymphoma showed that lymphomas involving sinuses without nasal involvement were predominantly DLBCLs (20 of 21), whereas nasal cavity lymphomas without sinus involvement were usually NK/T-cell type (8 of 11) (p = 0.000125). Compared with patients with DLBCL, patients with nasal NK/T-cell lymphoma were overall younger, with a lower male-to-female ratio. Lymphomas of B-cell lineage were more likely to be associated with symptoms related to the eyes (p < 0.0005) and to have extension to the orbit (p < 0.01) than were lymphomas of T- or NK-cell lineage. In contrast to results of Asian studies in which nasal NK/T-cell lymphoma has a very poor prognosis, our nasal NK/T-cell lymphomas had an outcome similar to that of DLBCL.

Microscopic evaluation of all adult tonsillar specimens has been considered essential despite the low incidence of unsuspected pathologic conditions. We evaluate whether routine histologic examination of clinically benign adult tonsillar specimens is indicated. We retrospectively reviewed pathology results from all tonsillectomies performed on patients ages 18 years or older at our institution from 1989 through 1996. Three groups were created on the basis of indications for tonsillectomy: (1) routine tonsillectomies for benign disease, (2) asymmetric tonsils, and (3) search for unknown primary lesions. Demographic data and pathologic findings in each group were analyzed. In 1280 tonsillectomies performed for benign disease there were no malignancies (0%) and 32 cases (2.50%) with clinically unsuspected benign pathologic conditions. In 31 cases of tonsillar asymmetry, two cases with malignant lymphoma (6.5%) and three cases with benign pathology (9.7%) were identified. In nine patients with squamous cell carcinoma metastatic to the neck, two occult primary lesions were identified in the ipsilateral tonsil. Our results suggest that histologic evaluation of adult tonsils removed for benign disease may be clinically unnecessary. The elimination of microscopic examination of tonsils removed from patients whose clinical presentation is entirely consistent with benign disease poses minimal risk of missing clinically significant pathologic conditions. Substantial costs for negative examinations may be avoided.

Increased expression of the cell adhesion molecule, CD44 standard form (CD44s), has been associated with papillary epithelial tumors, and decreased expression has been linked to tumor invasion and metastasis. Sinonasal inverted papillomas (SIPs) are the most common papillary tumors of the sinonasal tract. This study tests whether the development of squamous cell carcinoma (SCC) in situ and invasive SCC in SIP is associated with altered expression of CD44s. Seventy-six specimens of SIP from 68 patients, 2 specimens of SIP with focal SCC in situ, and 10 specimens of invasive SCC arising in SIP were studied. Automated immunohistochemistry was performed for CD44s expression on paraffin-embedded tissue sections using mouse antihuman CD44 antibody. All 76 SIPs (100%) expressed CD44 (strong membranous staining, 83%; moderate staining, 12%; weak staining, 5%). Two (100%) of 2 SIPs with SCC in situ maintained strong expression in benign and severely dysplastic foci. Six (60%) of 10 SIPs with SCC showed complete loss of CD44s expression, while 4 (40%) of 10 cases of SIP with SCC showed weak expression. Two SIPs with SCC (20%) featured weak diffuse staining of the SCC component, and 2 SIPs with SCC (20%) featured weak focal staining of the SCC component. The non-SCC SIP components of the 10 SIPs with SCC uniformly featured intact membranous CD44 staining. As in other papillary epithelial neoplasms, the typical benign SIP features diffuse membranous CD44s expression. In cases of SIP developing an invasive SCC, CD44s expression in the SCC component is frequently lost.

We describe two cases of a distinctive in situ and invasive cutaneous adnexal neoplasm occurring in the eyelid. Mucinous carcinoma represented the invasive portion of the tumor in one case, whereas the other infiltrated in small solid nests. The in situ component is identical to the recently described solid papillary carcinoma of the breast (endocrine ductal carcinoma in situ). Both tumors produced intra- and extracellular mucin, exhibited endocrine differentiation by immunohistochemistry and ultrastructural analysis, and were positive for estrogen and progesterone receptors.

Eosinophilic angiocentric fibrosis (EAF) is a rare condition of unknown etiology that causes stenosis of the upper respiratory tract. We report one case in which immunohistochemical studies were performed that involved the mucosa of the lateral nasal wall and septum of a 54-year-old woman. The lesion showed areas with vascular proliferation, small-vessel vasculitis, and dense inflammatory infiltrate consisting of T lymphocytes, macrophages, polyclonal plasma cells, and numerous eosinophils and neutrophils. Other areas were hypocellular and fibrotic, and in those, the collagen bundles showed perivascular onion-skin whorling. The clinical and histologic similarities between our case and those previously described, in addition to the immunohistochemical findings, support the hypothesis that eosinophilic angiocentric fibrosis is a chronic inflammatory condition with a peculiar and striking stromal response.

Aggressive papillary tumors of the temporal bone, occurring sporadically or as part of von Hippel-Lindau disease, have been shown to originate within the endolymphatic sac or duct. Also implicated as a potential precursor from which some of these tumors may arise is ectopic choroid plexus epithelium. To aid in the differentiation between papillary tumors of endolymphatic sac and duct origin and those arising from choroid plexus, an immunohistochemical study using stains for transthyretin (TTR), cytokeratins, S-100 protein, epithelial membrane antigen (EMA), and glial fibrillary acidic protein (GFAP) was carried out on archival specimens of normal and neoplastic endolymphatic sac and duct and choroid plexus epithelium. Transthyretin, a marker for choroid plexus epithelium, was found to show differential expression between choroid plexus papillomas and aggressive papillary tumors of the endolymphatic sac or duct. Therefore the use of TTR in concert with other immunohistochemical stains appear to aid in the differentiation between intracranial and intratemporal papillary tumors arising from choroid plexus and endolymphatic sac or duct epithelium.

A 31-year-old woman had bilateral swelling of the parotid glands at 4 months of pregnancy. MR imaging showed marked enlargement of the parotid glands with increased signal on images with long repetition times. A diagnosis of polycystic disease of the parotid gland was made after biopsy and histologic examination. The radiographic and histologic features of this rare disease are discussed.

Although intraepithelial pigment in the prostate gland has been termed melanosis, the nature of the pigment is not entirely clear, and many pathologists are not aware of its existence. We examined 863 hematoxylin and eosin (H + E) stained slides from 150 surgical specimens of prostate (69 needle biopsies, 66 transurethral resections, 14 radical prostatectomies, and 1 suprapubic prostatectomy) from 149 patients (age range, 47 to 90 years; mean 70 years) in an effort to characterize this pigment. The 1-3 microns in diameter, predominantly subnuclear, yellow-brown to gray-brown granules with a dark blue rim (by H + E) stained positively with Fontana-Masson, periodic acid-Schiff with diastase, Congo red, luxol fast blue, and oil-red-O and exhibited yellow autofluorescence consistent with lipofuscin. H + E stained slides revealed pigment in the benign epithelium in 86 of 150 cases (57%), within stromal macrophages in eight cases, and in atypical epithelium in two cases of high-grade prostatic intraepithelial neoplasia. Ten cases of invasive adenocarcinoma without recognizable pigment in H + E stained sections were stained by the Fontana-Masson technique, and pigment was identified in malignant epithelium in three of these cases. Ultrastructural examination of intraepithelial pigment in KII-fixed tissue from three radical prostatectomy specimens demonstrated the typical appearance of lipofuscin. Although intraepithelial pigment in prostatic biopsy or resection specimens is usually considered characteristic of seminal vesicle epithelium, our study demonstrates that lipofuscin is commonly present in epithelial cells of benign prostatic hyperplasia and less frequently in those of prostatic intraepithelial neoplasia and adenocarcinoma. The recognition of this pigment is important in preventing diagnostic confusion with seminal vesicle epithelium and with melanocytic lesions.

We report three cases of an orbital soft tissue lesion that fulfills the histologic, immunohistochemical, and electron microscopic criteria for solitary fibrous tumor, an entity previously described as a pleural tumor, but recently reported to occur in other locations. All three patients presented with proptosis. Two of the patients were cured by simple excision, and one patient had two recurrences, the last recurrence incompletely excised. The findings indicate that solitary fibrous tumor can occur in the orbit and, like solitary fibrous tumors of other anatomic sites, may behave in a nonaggressive or occasionally, locally aggressive fashion, with as yet no metastatic potential demonstrated in orbital lesions.

Hamartomas are easily diagnosed entities when occurring in the lung and gastrointestinal tract. In the nose and nasopharynx, where such lesions are rare, biopsy of a hamartoma containing epithelial proliferation may lead to a misdiagnosis of cancer, with resultant radical and deforming surgery, particularly if they present in adulthood. We encountered three such lesions over 2 years in the Massachusetts Eye Ear Infirmary, and another was retrieved from the recent files. All presented with nonspecific obstructive symptoms of the nose or nasopharynx, and were treated by resection. Follow-up is short, (4 months to 1 year), but in no case has there been recurrence. The clinical diagnosis was malignancy in 2 cases, inflammatory polyp in one.

We report two solitary fibrous tumors of the nasal cavity and paranasal sinuses that were histologically and immunohistochemically virtually identical to solitary fibrous tumors (fibrous mesotheliomas) of the pleura. One tumor arose in a 48-year-old woman and the other in a 45-year-old woman. Both patients presented with nasal symptoms, and both patients are alive without evidence of disease 6 months and 1 year after excision. The tumors had a disorganized or "patternless" arrangement of spindle cells in a collagenous background and prominent vascular channels of varying size. Immunoperoxidase stains on paraffin sections showed staining of the cells for vimentin only; there was no staining for keratin, S-100 protein, desmin, and actin. Both cases presented some degree of diagnostic difficulty and had to be distinguished from other spindle cell tumors of the nasal cavity and paranasal sinuses, such as hemangiopericytoma, angiofibroma, and fibrous histiocytoma.

Two cases of olfactory neuroblastoma mixed with other neoplastic elements are reported. One tumor contained foci of adenocarcinoma and of ganglioneuroblastoma in addition to an undifferentiated small cell component consistent with neuroblastoma; the other tumor histologically resembled small cell undifferentiated carcinoma with foci of squamous differentiation, but was shown by electron microscopy to be neuroblastoma. The histogenesis and treatment of mixed tumors of this type are discussed.

Sixty-three serum specimens from American patients with nasopharyngeal carcinoma were examined for antibodies to antigens associated with Epstein-Barr virus (EBV) and compared with 98 specimens from patients with other head and neck cancers, 133 from patients with benign head and neck diseases, and 96 from healthy donors. The level of antibody titers to EBV-associated antigens was correlated with nasopharyngeal carcinoma. The anti-EBV profile of elevated antibody titers directed against viral capsid antigen and early antigen was seen in undifferentiated and nonkeratinizing tumors but usually not in squamous cell tumors. Titers tended to rise with large increases in total tumor burden caused by distant metastases, often before clinical evidence of metastases. At the time of diagnosis, antibody-dependent cellular cytotoxicity testing was performed on serum samples from 46 of the patients with nasopharyngeal carcinoma. Pretreatment titers were usually low in patients in whom recurrence developed and were high in most of the patients who had a good response to treatment and have remained free of recurrence.

Laryngeal paraganglioma, carcinoid tumor, and small-cell carcinoma are rare. Histologically they are similar to analogous tumors in other locations but may be difficult to identify in small biopsy specimens. We compared the light microscopic, histochemical, immunohistochemical, and electron microscopic features of two laryngeal paragangliomas, one carcinoid tumor, and six small-cell carcinomas. The paraganglioma chief cells stained with Grimelius stain and for chromogranin and neuron-specific enolase. The carcinoid tumor cells stained with Grimelius stain and for chromogranin, serotonin, neuron-specific enolase, and keratin. The small-cell carcinoma cells stained for keratin and neuron-specific enolase. The patients with paragangliomas and carcinoid tumor remain healthy through 20 months of follow-up. Four of the patients with small-cell carcinomas have died. Distinction between these tumors is warranted by differing histologic appearances, staining characteristics, and biologic behavior.

Mucoepidermoid carcinoma of the lacrimal sac was diagnosed in a 62-year-old woman who presented with epiphora and a fixed painless mass in the area of the lacrimal sac. Histopathologic findings included nests and islands of neoplastic cells in a fibrotic stroma. The tumor nests contained both glandular spaces and solid epithelial areas. Treatment entailed dacryocystectomy with silastic intubation and subsequent medial maxillectomy and ethmoidectomy. The patient was tumor free on 1-year follow-up. Clinical features, histopathological findings, prognosis, and management of this rare tumor are reviewed in this article.

From 1978 to 1981, 151 patients with nasopharyngeal carcinoma (NPC) were enrolled in a prospective, collaborative study of North American patients, most of them white. Thirty-seven had World Health Organization (WHO) type 1 tumors, and 114 had WHO types 2 and 3 tumors. The anti-Epstein-Barr virus (EBV) profile of elevated antibody titers directed against viral capsid antigen and early antigen was seen in 85% of the patients with WHO types 2 and 3 tumors but in only 16% of the patients with WHO type 1 tumors. Geometric mean titers tended to be higher in higher stages of the disease in several staging systems. Low antibody-dependent cellular cytotoxicity at diagnosis appears to reflect a poorer prognosis, and the determination of antibody titers by this assay may prove to be useful for identifying persons in whom recurrent disease is likely to develop after conventional therapy. Anti-EBV titers can aid in diagnosis and treatment planning in patients with NPC, particularly those with occult primary NPC.

A patient had fetal cellular rhabdomyoma of the larynx confirmed histologically and by electron microscopy. The literature on laryngeal rhabdomyomas is reviewed. Adult and fetal rhabdomyomas demonstrate no clinical differences in the larynx, unlike rhabdomyomas described elsewhere in the body. Most patients are middle-aged men with less than three years' history of hoarseness. The diagnosis is established pathologically by using routine histologic criteria, special stains, and electron microscopy. Treatment consists of local surgical excision. The tumors rarely recur.

Immunohistochemical staining for keratin proteins may be useful as a diagnostic parameter in head and neck neoplasms. Our study evaluates the keratin antibody staining properties of normal tissues as well as neoplastic and non-neoplastic head and neck lesions from surgical procedures performed on 100 patients. The results indicate that the anti-keratin antibody technique can be helpful in several areas of head and neck pathology.

Heterotopic cervical salivary gland tissue was found in a 4-yr-old girl with branchial and otologic abnormalities. Her mother and sister also had heterotopic cervical salivary tissue in association with anomalies that suggest the branchio-otorenal (BOR) syndrome. Heterotopic cervical salivary gland tissue may result from abnormal branchial development.

The distinction between benign and malignant lymphoid infiltrates of the orbit may be impossible on routine histopathologic sections. However, the detection of monotypic immunoglobulin is useful in distinguishing neoplastic from benign infiltrates. Since diagnostic frozen sections are often performed on biopsies of orbital masses to determine the adequacy of the biopsy and to provide a preliminary diagnosis, we stained additional frozen sections of 20 predominantly lymphoid infiltrates by an immunoperoxidase technique with antisera to immunoglobulin heavy and light chains. On routine sections, nine cases were malignant lymphoma, three were follicular hyperplasia, and eight (42%) were dense lymphocytic infiltrates of indeterminate nature. The nine lymphomas had monotypic immunoglobulin staining. The three histologically benign lesions had polytypic immunoglobulin. Six of the eight indeterminate lesions had monotypic immunoglobulin, supporting a diagnosis of lymphoma; two had polytypic staining. There was evidence of disseminated lymphoma at the time of diagnosis in five of nine patients with histologically malignant lesions and three of five with monoclonal indeterminate lesions for whom the information was available. Staining with monoclonal antibodies to T-cells revealed variable numbers of T-cells in all cases; their number and distribution did not distinguish benign from malignant lesions. The immunoperoxidase technique on frozen sections permits optimal use of small biopsy specimens for both morphologic and immunologic diagnosis. The majority of histologically indeterminate orbital lymphoid infiltrates were shown to be monoclonal.

Nasopharyngeal carcinoma (NPC) provides a unique opportunity to evaluate distinctive epidemiologic features and a possible etiologic relationship with Epstein-Barr virus (EBV) in human malignancy. The lack of a uniformly accepted pathologic classification for NPC has limited the application of this data, although the World Health Organization (WHO) developed a classification that may solve this problem. Monoclonal keratin antibodies were used for staining of NPC for evaluation of its assistance in diagnosis and classification. In the present immunohistochemical study, monoclonal keratin antibodies, designated AE1, AE2, and AE3, and a polyclonal keratin antibody (RAK) were used for study of the presence of keratin in 121 cases of NPC obtained from China and the United States. AE1 monoclonal antibody, which recognizes keratin protein classes 56.5K, 50K, and 40K, was shown to be the most sensitive and specific for NPC tumor cells among the keratin antibodies studied. In addition, some different keratin expression patterns could be identified between different kinds of epithelium and different tumor groups, with possible relevance to the histogenesis of the histologic subtypes of NPC.