Adenoid cystic carcinoma of the lacrimal gland is frequently characterized by MYB rearrangement.

PurposeAdenoid cystic carcinoma (ACC) represents ~10-15% of salivary neoplasms and almost universally exhibits a lethal clinical course. ACC is also known to occur in the lacrimal gland. ACC is characterized by its heterogeneous morphology and may demonstrate tubular, cribriform, and/or solid architectural patterns. Unfortunately, these histopathological features are not specific to ACC and can be seen in other salivary gland-type neoplasms, introducing a diagnostic dilemma. The discovery of fusion transcripts has revolutionized the diagnosis, surveillance, and treatment of epithelial malignancies. In several anatomic subsites ACC is frequently characterized by a fusion transcript involving genes MYB and NFIB; more specifically, t(6;9)(q22-23;p23-24). This study explores the incidence of MYB rearrangement in cases of lacrimal gland ACC using fluorescent in situ hybridization.Materials and methodsRetrospective clinical and histopathological review of 12 cases of lacrimal gland ACC seen at Mayo Clinic over a 25-year period (1990-2015) was performed. Demographic and clinical data were obtained from medical records. Surgical pathology archival material including H&E slides and immunostains was re-examined. Formalin-fixed paraffin-embedded material was further evaluated using immunohistochemistry when appropriate. Fluorescent in situ hybridization (FISH) using a MYB break-apart probe was applied to all histologically confirmed cases of ACC and benign salivary gland parenchyma.ResultsThe median patient age was 53.6 years (range 12-64) and distributed equally by gender (six male and six female). Rearrangement of MYB was identified using FISH in seven cases (58%). Twenty-five sections of benign salivary gland parenchyma showed no evidence of MYB rearrangement. Primary surgical resection was most common treatment, and 78% of the patient received adjuvant radiation therapy. Median overall survival (OS) was 11 years. Rearrangement of MYB did not affect OS.ConclusionsIn summary, our results indicate that the MYB rearrangement defines a significant subset of lacrimal gland ACCs. Importantly, FISH for MYB rearrangement may be used as a diagnostic tool during pathological examination of lacrimal gland neoplasms. Our results showed no relationship between rearrangement status and clinical outcome. Lastly, the presence of t(6;9) in ACC may provide a platform for molecular-targeting strategies in the future.

Immunoglobulin G4-related disease of the orbit: imaging features in 27 patients.

BACKGROUND AND PURPOSE: Immunoglobulin G4-related disease is a systemic fibroinflammatory process of unknown etiology, characterized by tissue infiltration by immunoglobulin G4 plasma cells. The purpose of this study was to retrospectively identify the spectrum of imaging features seen in immunoglobulin G4-related disease of the orbit. MATERIALS AND METHODS: This study included 27 patients with biopsy-proved immunoglobulin G4-related disease of the orbit and either a CT or MR imaging of the orbits. These CT or MR imaging examinations were evaluated for the following: extraocular muscle size, extraocular muscle tendon enlargement, lacrimal gland enlargement, infiltrative process in the orbital fat (increased attenuation on CT or abnormal signal on MR imaging), infraorbital nerve enlargement, mucosal thickening in the paranasal sinuses, and extension of orbital findings intracranially. RESULTS: Extraocular muscles were enlarged in 24 of 27 (89%) patients, 21 (88%) bilaterally. In 32 of 45 (71%) affected orbits, the lateral rectus was the most enlarged muscle. In 26 (96%) patients, the tendons of the extraocular muscles were spared. Nineteen (70%) patients had lacrimal gland enlargement. Twelve (44%) patients had an infiltrative process within the orbital fat. Infraorbital nerve enlargement was seen in 8 (30%) patients. Twenty-four (89%) patients had sinus disease. Cavernous sinus or Meckel cave extension was seen in 3 (11%) patients. CONCLUSIONS: In patients with extraocular muscle enlargement, particularly when the tendons are spared and the lateral rectus is the most enlarged, and even more so when other noted findings are present, immunoglobulin G4-related disease should be a leading differential consideration, even over more commonly known etiologies of extraocular muscle enlargement.

Dermal and conjunctival melanocytic proliferations in diffuse uveal melanocytic proliferation.

AIM: The goal of this case report is to describe the dermatologic and conjunctival findings in a case of bilateral diffuse uveal melanocytic proliferation (BDUMP), a paraneoplastic syndrome usually associated with gynecologic cancers. There is little information about other dermatologic melanocytic findings in these patients. METHODS: Histologic and fluorescent in situ hybridization (FISH) analysis of three separate skin biopsies, one of which was separated by 21 months from the others, were performed in a 71-year-old patient with BDUMP to assess for histologic and chromosomal abnormality. Conjunctival histologic evaluation was also done. RESULTS: Dermal melanocytic proliferation was seen in each specimen. The cells were spindle type with mitotic activity. FISH analysis showed a normal copy of chromosomes. The conjunctival sample also showed normal FISH analysis. CONCLUSION: BDUMP is associated with multifocal dermal and conjunctival melanocytic proliferation.

Chorioretinitis and vitreitis due to Tropheryma whipplei after transplantation: case report and review.

Whipple's disease is a very rare chronic multisystemic bacterial disease characterized by diarrhea, malabsorption, fever, and polyarthritis. Ocular manifestations occur very rarely. Previous reports have suggested that the use of immunosuppressive drugs appears to accelerate or exacerbate the clinical course of Whipple's disease; however, the illness has yet to be reported in the setting of transplantation. Herein, we describe what we believe is the first reported case of Whipple's disease after transplantation. The patient is a 51-year-old woman who developed progressive visual floaters and blurring of vision 30 years after living-related kidney transplantation for an autosomal-dominant polycystic kidney disease. Her allograft was functioning well on maintenance immunosuppressive therapy with azathioprine and prednisone when she developed visual abnormalities. Transient weight loss, gastrointestinal symptoms, and migratory polyarthralgia predated the onset of ocular disease by several years. The diagnosis of Whipple's bilateral vitreitis and chorioretinitis was confirmed by polymerase chain reaction analysis demonstrating Tropheryma whipplei nucleic acid in vitreous fluid and peripheral blood sample as well as by demonstration of the bacilli by cytopathology. Intraocular vancomycin, intravenous ceftriaxone, and prolonged course of oral trimethoprim-sulfamethoxazole therapy led to clinical improvement and recovery of visual acuity.

Intraocular use of rituximab.

PURPOSE: To evaluate the toxicity of 1 mg of intraocular rituximab and to present a small case-series of patients treated with intravitreal rituximab. METHODS: Rituximab (1 mg/0.1 ml) was injected in the vitreous of one eye of three Dutch-belted rabbits. Two animals were injected with balanced salt solution as controls. At 1 month the rabbits were killed and the eyes examined by light microscopy. Three patients (five eyes) with intraocular lymphoma were also treated with a 1 mg injection of rituximab. RESULTS: The treated rabbit eyes and the control eyes showed no light microscopic evidence of ocular toxicity at 1 month following injection. The five human eyes of three patients have shown no evidence of intraocular toxicity with a median follow-up time of 3.6 months (range 2.0-6.4 months). One patient received a total of four injections in the right eye and three injections in the left eye. CONCLUSION: Intravitreal rituximab at a dose of 1 mg does not appear to cause toxicity in rabbit eyes and in the five eyes of three patients.

Radiation-induced meningiomas involving the orbit.

PURPOSE: To review the clinical features and outcomes of patients with radiation-induced meningiomas involving the orbit. DESIGN: Retrospective case series. PARTICIPANTS: Eight patients with radiation-induced meningiomas affecting the orbit. METHODS: Clinical and pathologic data of the patients were reviewed. MAIN OUTCOME MEASURES: Age at diagnosis, mean interval between radiation therapy and meningioma diagnosis, tumor recurrence, histologic atypia, and mean follow-up time after initial diagnosis. RESULTS: The mean age at diagnosis was 42 years (range, 21 years to 70 years). The mean interval between radiation therapy and meningioma diagnosis was 26 years (range, 3 years to 54 years). All patients underwent gross total resection or subtotal resection of the meningioma. Five tumors (62.5%) recurred, based on clinical findings and CT imaging. The mean interval between resection of the meningioma and recurrence was 3 years (range, 9 months to 9 years). Three patients (37.5%) had atypical meningiomas. One patient (12.5%) had multiple tumors. The mean follow-up interval was 7 years after initial diagnosis of the meningioma (range, 15 months to 19 years). CONCLUSIONS: This series of radiation-induced meningiomas, the first in the ophthalmic literature, illustrates the aggressive nature of this tumor.

Characterization of a spontaneously arising murine squamous cell carcinoma (SCC VII) as a prerequisite for head and neck cancer immunotherapy.

BACKGROUND: To develop novel therapeutic approaches for patients with head and neck malignancies, poorly immunogenic murine models of squamous cell carcinoma (SCC) need to be defined. METHODS: The phenotype, growth characteristics, and responsiveness to tumor-specific T-cell transfer of a spontaneously arising murine SCC (SCC VII) were characterized. RESULTS: SCC VII expresses major histocompatibility complex (MHC) class I molecules yet is resistant to tumor-specific T-cell killing and relatively insensitive to killing mediated by lymphokine-activated killer (LAK) cells. Intradermal tumors are reproducibly established after vaccination of 5 x 10(4) cells, and systemic micrometastases are apparent after intravenous administration of 2.5 x 10(4) cells. Immunotherapy of 3-day lung metastases using tumor-specific T cells and systemic interleukin-2 (IL-2) was ineffective in reducing the number of metastases in vivo. CONCLUSIONS: SCC VII is a poorly immunogenic murine squamous cell cancer, which represents an ideal model for preclinical testing of immunotherapeutic approaches for patients with SCC of the upper aerodigestive tract.

Solitary fibrous tumor: a study of cytologic features of six cases diagnosed by fine-needle aspiration.

Solitary fibrous tumor (SFT) is a spindle-cell neoplasm most often presenting as a pleural-based tumor but increasingly recognized in other locations. Few reports have described the cytologic features of SFTs. Six cases of SFT diagnosed by fine-needle aspiration (3 pleura, 2 retroperitoneum, and 1 orbit) were identified in the Mayo Clinic files. The smears (Papanicolaou-stained) and corresponding histologic specimens were reviewed. Immunohistochemical staining for CD34 was performed in all cases. The cytologic findings were similar in all cases. The tumor cells were oval to polygonal, with cellularity ranging from scant to moderate. The background contained irregular ropy fragments of collagen and a few inflammatory cells. Most cells were dispersed singly, but all cases contained irregular, loose aggregates of cells enmeshed in a collagenous matrix. The nuclei were uniformly bland, with evenly distributed, finely granular chromatin. All cases were immunoreactive for CD34. SFT has distinctive cytologic features that allow diagnosis in cytologic specimens with the help of appropriate immunocytochemical stains on accompanying tissue biopsy specimens. Distinctive cytologic findings predictive of clinical behavior were not identified.

Adrenocortical carcinoma metastatic to the orbit.

PURPOSE: To describe the clinical course and histopathologic features of a patient with adrenocortical carcinoma metastatic to the orbit. METHODS: Case report and literature review. RESULTS: A 24-year-old man first came to medical attention because of symptoms referable to a 4.47-kg, nonfunctioning carcinoma of the left adrenal cortex. Several metastases ensued, including a large tumor to the right superior lateral bony orbit with extension to the brain, temporalis fossa, and orbit proper. The tumor was resected with the use of a combined neurosurgical, ophthalmic, and craniofacial approach. The patient died of widespread metastatic disease 15 months after the orbital operation. CONCLUSIONS: Metastasis to the orbit from adrenocortical carcinoma is rare. Surgical resection is the treatment of choice, with adjunctive radiation therapy and chemotherapy in some cases. The prognosis is poor.

Paraneoplastic and metastatic neurologic complications of Merkel cell carcinoma.

Merkel cell carcinoma is a rare primary cutaneous neuroendocrine tumor that is locally aggressive and frequently accompanied by distant metastases. Neurologic complications of Merkel cell carcinoma are rare. We describe a 69-year-old man who presented with Lambert-Eaton myasthenic syndrome and was found to have Merkel cell carcinoma. The paraneoplastic syndrome improved with initial treatment of the malignancy. He subsequently developed a solitary brain metastasis and died of leptomeningeal carcinomatosis.

Small cells in cervical-vaginal smears of patients treated with tamoxifen.

BACKGROUND: "Small cells" have been described in the cervical-vaginal (Papanicolaou [Pap]) smears of patients receiving tamoxifen. The current study determined the frequency of this finding and its implications for the differential diagnosis. METHODS: A computer-based search of the cytopathology files from January 1994 to December 1998 was performed for Pap smears from patients with a history of tamoxifen treatment. All smears were reviewed for the presence of "small cells" and endometrial cells. Pap smears from an age-matched control group that was not treated with tamoxifen also were screened for "small cells." RESULTS: Five hundred forty-eight Pap smears were identified from 425 patients (mean age, 62 years; average duration of treatment, 43 months). Clusters of these "small cells" were present in 104 Pap smears from 86 patients (19%). The background pattern was proliferative in the majority of the Pap smears (83%). In five Pap smears (5%), these "small cells" were interpreted originally as endometrial cells. In the remaining Pap smears, no reference to the presence of the cells was made in the original report. "Small cells" were identified in 79 Pap smears (18%) in the control group (n = 443 smears). CONCLUSIONS: The incidence of "small cells" is similar in the Pap smears of patients with or without a history of tamoxifen treatment. These cells are similar to reserve cells noted in atrophic smears. However, as a result of the proliferative effect of tamoxifen in the cervical epithelium, these cells are prominent when admixed with superficial and intermediate cells in patients treated with tamoxifen. These cells need to be differentiated from endometrial cells to avoid unnecessary follow-up procedures. Cancer (Cancer Cytopathol)

Myofibroblastoma and solitary fibrous tumour of the breast: histopathologic and immunohistochemical studies.

Thirteen mesenchymal tumours of the breast were reviewed histologically and immunohistochemically. Nine tumours (male:female ratio 5:4, average age 64 years) were classified as myofibroblastomas and presented as a single nodule (four) or a multilobular mass (five). They were composed of elongated cells with vesicular nuclei showing grooves, intranuclear inclusion, and small but conspicuous nucleoli resembling myofibroblasts seen in scar tissue. In six tumours, hypercellular zones alternated with paucicellular, hyalinized areas. The collagen pattern was dense, diffuse, and brightly eosinophilic in all neoplasms. The tumour cells were positive for desmin, actin, and vimentin in all nine lesions, and in six tumours a focal CD 34 positivity was also demonstrated. Four tumours (four female patients, average age 75 years) were classified as solitary fibrous tumours and consisted of well-circumscribed nodules. They were characterized by a monomorphic population of thin, spindled to ovoid cells with finely dispersed chromatin and inconspicuous nucleoli. The pattern of the collagen in these tumours was one of thick, brightly eosinophilic bands. These four tumours were negative for all markers tested except vimentin and CD 34. Although myofibroblastomas and solitary fibrous tumours of the breast share many morphologic features, there are enough differences in their cytologic composition and, most importantly, in their immunohistochemical profile to consider them as distinct entities.

Papillary thyroid cancer with pulmonary metastases in children: long-term prognosis.

BACKGROUND: Papillary thyroid cancer (PTC) in young patients may rarely be encountered with pulmonary metastases. Previous studies have suggested that, in the pediatric population, this may not portend a lethal outcome. Our present study, children with pulmonary metastases, was designed to clarify this issue. METHODS: Fourteen children and young adolescents (mean age, 13.5 years; range, 9.8-17 years) with PTC and pulmonary metastases were treated at our institution between 1937 and 1998. Surgical treatment consisted of total thyroidectomy (n = 10 patients), subtotal thyroidectomy (n = 3 patients), and a biopsy only procedure (n = 1 patient). All patients who underwent thyroidectomy also underwent a variety of cervical lymph node dissections, and all patients proved to have regional nodal disease. After the operation, 12 patients were treated with ablative doses of (131)I, 1 patient was treated with external beam irradiation, and all patients were placed on suppressive thyroid hormone therapy. The mean length of follow-up was 19.3 years (range, 1-45 years). RESULTS: Regional recurrent disease developed in 2 patients (15%). No patient experienced the development of worsening pulmonary disease or extra-pulmonary metastases. All patients with recurrent disease underwent selective nodal resections. No patient died of metastatic PTC. Seven patients (50%) remain completely free of disease and are probably cured; 7 patients (50%) are asymptomatic with residual pulmonary disease. CONCLUSIONS: A stepwise treatment approach allows long-term survival and frequent cure for young patients with PTC and concomitant pulmonary metastases.

Laser pointers and the human eye: a clinicopathologic study.

We report the absence of photic retinal injury after exposing the retina to light from class 3A laser pointers for durations of up to 15 minutes. Three patients with uveal melanomas were scheduled to have an enucleation. Each agreed to have his or her retina exposed to laser light from a class 3A laser pointer prior to enucleation. Continuous exposure was directed to the fovea for 1 minute, to the retina 5 degrees below fixation for 5 minutes, and to the retina 5 degrees above fixation for 15 minutes. Ophthalmoscopic evaluation of the cornea, lens, and retina and fluorescein angiographic studies of the retina were conducted before, 24 hours after, and 11 days after laser exposure in the first case; before and 86 hours after exposure in the second case; and before, 96 hours after, and 15 days after exposure in the third case. Other than transient afterimages that lasted only a few minutes, we were unable to document any functional, ophthalmoscopic, fluorescein angiographic, or histologic evidence of damage to any structures of the eyes. Transmission electron microscopic studies of retinal sites targeted by the laser pointers in the second and third cases revealed ultrastructural abnormalities in the outer retina and the pigment epithelium that were similar to abnormalities seen in the retina approximately 8 mm away from the targeted sites. The risk to the human eye from transient exposure to light from commercially available class 3A laser pointers having powers of 1, 2, and 5 mW seems negligible.

Effect of clinical history on diagnostic accuracy in the cytologic interpretation of bronchial brush specimens.

There has been little study of the effect of clinical history on pathologic diagnostic accuracy. Five pathologists retrospectively examined 97 bronchial brush specimens with and without clinical historic information. Forty-nine patients had a biopsy-proven malignant lesion, and 48 had a benign lesion. Diagnostic accuracy with and without history for each pathologist was determined with likelihood ratios and receiver operating characteristic curves. The overall diagnostic accuracy with and without history was 0.84 and 0.76, respectively. The average negative predictive value of a benign diagnosis decreased from 89.2% (with history) to 74.0% (without history). Overall, the cytopathologists were more reluctant to make a definitive malignant diagnosis without history compared with history. The average positive predictive value of a malignant diagnosis with and without history was almost identical. The absence of history leads to lower diagnostic accuracy in the cytologic interpretation of bronchial brush specimens partly because pathologists underdiagnose malignant lesions.

Cytologic changes in the conjunctiva mimicking malignancy after topical mitomycin C chemotherapy.

PURPOSE: To describe the epithelial changes observed in the conjunctiva secondary to the use of topical mitomycin C (MMC) for treatment of primary acquired melanosis with atypia. DESIGN: Retrospective comparative case series. PARTICIPANTS AND CONTROLS: Conjunctival biopsy specimens (18) were taken during the follow-up of ten patients treated with MMC drops (0.02% or 0.04%) during 14 or 21 days for primary acquired melanosis with atypia. An equal number of age- and sex-matched patients with normal conjunctival biopsy findings were included for control. Conjunctival biopsy specimens from patients treated with MMC were compared with the morphologic changes already described in the urothelium following the use of the same chemotherapeutic agent. METHODS: Hematoxylin and eosin-stained biopsy samples were evaluated for recurrent neoplasm and chemotherapeutic effect in the epithelium using the following criteria: nuclear enlargement, nuclear hyperchromasia, smudging of the chromatin, presence of nucleoli, cytoplasmic eosinophilia, and individual cell necrosis. MAIN OUTCOME MEASURES: The presence or absence of morphologic changes in the conjunctival epithelium related to the use of MMC. RESULTS: Morphologic features consistent with chemotherapy effect were seen in the biopsy specimens of nine patients. Nuclear enlargement and chromatin smudging-hyperchromasia localized in the superficial layers of the epithelium were the main features observed (9 patients). Cytoplasmic eosinophilia, single cell necrosis, and occasionally subepithelial chronic inflammation were also seen. CONCLUSIONS: Secondary changes with the topical use of MMC are seen in the conjunctival epithelium and are similar to the changes described in the urothelium. These changes are important to recognize and to differentiate from recurrent neoplasm. The localization of the described features in the superficial layers of the conjunctival epithelium is the key feature in the differential diagnosis.

Fine-needle aspiration cytology of esophageal leiomyomatosis.

Leiomyomata are the most common benign neoplasms of the esophagus, but they are still very rare in comparison to malignant tumors of this organ. We report on the aspiration cytology findings of a case of esophageal leiomyomatosis in a 19-yr-old man. Diagn. Cytopathol. 1999;21:197-199.

Cellular schwannoma mimics a sarcoma: an example of a potential pitfall in aspiration cytodiagnosis.

Cellular schwannoma, a variant of benign schwannoma, is characterized by marked nuclear pleomorphism and hyperchromasia and may be overdiagnosed as a malignancy in fine-needle aspiration specimens. We report the aspiration cytology findings of a case of cellular schwannoma that arose in the parapharyngeal region of a 50-yr-old woman.

Rhabdomyosarcoma presenting as a parotid gland mass in pediatric patients: fine-needle aspiration biopsy findings.

BACKGROUND: The head and neck region is one of the most common locations of rhabdomyosarcoma. Salivary gland involvement is usually secondary to advanced disease, and presentation as a primary salivary gland tumor is very rare. METHODS: Three cases of rhabdomyosarcoma presenting as parotid masses, in 2 boys (ages 3 and 7 years) and a girl (age 5 years), were retrieved from the files of 2 institutions. RESULTS: The three patients presented with parotid gland enlargement. Clinically, the enlargements appeared to be inflammatory, and they were treated unsuccessfully with antibiotics. Fine-needle aspiration biopsy (FNAB) was performed on all three patients. The cytologic features varied from one case to another; one case had features of a small round cell tumor, another was composed of a monomorphic population of spindle cells in a metachromatic stroma, and the third case was composed mostly of spindle cells with moderate cellular pleomorphism. Immunohistochemical studies performed in two of the cases confirmed the diagnosis of rhabdomyosarcoma, and ultrastructural studies were confirmatory in the other case. The patients are alive; 2 of them have had no evidence of disease after 6 and 9 years of follow-up, and the third, the most recent patient, has just finished adjuvant chemotherapy. CONCLUSIONS: With the increased use of FNAB for the evaluation of salivary gland masses in children, the authors believe that it is important to recognize the occurrence of rhabdomyosarcoma in this location. Immunohistochemical studies have proved helpful in differentiating rhabdomyosarcoma from other parotid gland tumors and can be readily done on cytologic preparations.

Pancreatic cystic neoplasms: the role and sensitivity of needle aspiration and biopsy.

BACKGROUND: The proper evaluation of patients with pancreatic cystic neoplasms remains controversial. Although computed tomography (CT) and sonography can differentiate the majority of these tumors, needle aspiration and biopsy can be helpful in selected patients. The purpose of this study was to (1) determine the sensitivity of needle aspiration and biopsy of cystic pancreatic neoplasms, (2) assess the complications after needle aspiration and biopsy, and (3) assess the indications for needle aspiration and biopsy by using the radiographic appearance as a guide. METHODS: The histories, imaging studies, and pathologic specimens of 18 patients with serous cystadenoma (10 patients) or mucinous cystic tumor (eight patients) of the pancreas who also underwent CT-guided (n = 16), sonographically guided (n = 3), or intraoperative (n = 4) needle biopsy (n = 23 total biopsies) between 1976 and 1996 were retrospectively reviewed. RESULTS: The histologic diagnosis of the serous subtype was made with needle aspiration and biopsy in five of 10 patients with serous cystadenoma. The histologic diagnosis of the mucinous subtype was made with needle aspiration and biopsy in six of eight patients with mucinous cystic neoplasms. Of the 23 biopsies performed, one patient experienced significant intraperitoneal hemorrhage. Indications for needle biopsy include an atypical cystic mass on diagnostic imaging studies, confirmation of a serous cystadenoma before observation, and confirmation of mucinous cystadenocarcinoma in patients with nonresectable disease. CONCLUSION: Needle biopsy and aspiration is a helpful and safe procedure to aid in the diagnosis of cystic pancreatic neoplasms before surgery.