Phase I/IB study of immunization with autologous tumor cells transfected with the GM-CSF gene by particle-mediated transfer in patients with melanoma or sarcoma.

The objective of this Phase I study is to assess the acute and long-term toxicities of intradermal vaccination of cancer patients with lethally-irradiated tumor cells that have been transfected by particle-mediated gene transfer (PMGT) with gold particles coated with human granulocyte-macrophage colony stimulating factor (GM-CSF) DNA in a plasmid expression vector. The GM-CSF DNA-coated gold particles are delivered to tumor cells using helium pressure with a hand held gene delivery device. Preclinical studies have demonstrated that vaccination of mice with irradiated, GM-CSF-transfected melanoma cells provided protection from subsequent challenges with non-irradiated, non-transfected tumor cells. Ongoing human tumor immunotherapy studies use patients' melanoma or renal carcinoma cells transfected with a retroviral vector containing GM-CSF cDNA as a vaccine to elicit anti-tumor immune responses. PMGT transfection, unlike retroviral transfection, does not require tumor cells to proliferate in vitro to undergo gene transfer. Instead, tumor tissue can be dissociated into small tissue clumps or cell aggregates and then immediately transfected using the gene gun. PMGT physically inserts the DNA without the need for cell surface interaction with viral components or exposure of the patient to viral antigens. As described in this protocol, fresh human sarcoma and melanoma specimens can be transfected with the GM-CSF DNA-coated gold particles with subsequent production of biologically active GM-CSF protein. In this study tumor tissue will be obtained from patients with melanoma or sarcoma. Tumor tissue will be dissociated, irradiated, and transfected with GM-CSF DNA by PMGT. In this ascending dosage study, two dose levels of GM-CSF DNA will be studied in 2 groups of 6 patients each. Patients will receive two intradermal injections of the irradiated, transfected tumor in a single extremity. On days 3 and 14 post-vaccination, patients will undergo surgical excision of the vaccination sites to assess GM-CSF production and infiltration of immune effector cells. On Day 25, patients will undergo DTH testing with intradermal injection in their opposite extremity of 5 x 10(6) irradiated non-transfected autologous tumor cells cryopreserved at the time of vaccine preparation. This injection site will be assessed on day 28 post-vaccination and surgical excision of the DTH testing site will be performed on day 28 if a positive reaction is noted. The patients will be observed for local and systemic toxicity on days 2, 3, 5, 8, 14, 25, and 28 after the vaccination. Restaging of the patients' disease and long term toxicity evaluation will be performed at 3, 6, and 12 months and then yearly.

Heteropagus conjoined twins due to fusion of two embryos: report and review.

We report on a case of conjoined twinning (CT) consistent with fusion of two embryos followed by resorption of the cranial half of one of them, resulting in a normal male baby with the lower half of a male parasitic twin fused to his chest. Fluorescent in situ hybridization (FISH) studies suggested that the parasitic twin was male, and DNA typing studies demonstrated dizygosity. Although incomplete fission is the usual explanation for conjoined twins, the unusual perpendicular orientation of the parasite to the autosite supports a mechanism observed in mares in which early fusion of two embryos is followed by resorption due to compromised embryonic polarity.

Serous cystadenoma of the pancreas with papillary features: a diagnostic pitfall on fine-needle aspiration biopsy.

Serous cystadenoma of the pancreas is an uncommon neoplasm that occasionally exhibits papillary differentiation. The cytomorphologic structure of pancreatic serous cystadenoma has been rarely described, and, to our knowledge, such papillary morphologic structure has never been reported on fine-needle aspiration cytologic examination. We present a case of serous cystadenoma of the pancreas in a 77-year-old woman. Endoscopic ultrasonography showed a well-demarcated solid/cystic mass in the midbody of the pancreas, suggestive of solid pseudopapillary tumor. Aspiration cytologic examination, performed under endoscopic ultrasound guidance, showed a predominantly papillary epithelial neoplasm consistent with the radiologic impression. Gross and histologic examination of the excised specimen revealed a pancreatic serous cystadenoma with multifocal papillae. This case illustrates the cytomorphologic structure of serous cystadenoma that presents with prominent papillary differentiation on aspiration cytologic examination. The unusual cytologic appearance of this tumor introduces significant diagnostic challenges to the pathologist. Serous cystadenoma must be included in the differential diagnosis of pancreatic neoplasms with papillary morphologic structure as evaluated by fine-needle aspiration cytologic examination.

Diagnosis of primary fibrosarcoma of the lung by fine-needle aspiration and core biopsy.

Primary pulmonary sarcomas are uncommon neoplasms. Primary fibrosarcoma of the lung is extremely rare, and only 53 cases have been documented in the literature to date. To our knowledge, the diagnosis of primary lung fibrosarcoma by fine-needle aspiration cytology has never been reported. We report a case of pulmonary fibrosarcoma diagnosed by fine-needle aspiration cytology and core biopsy. The neoplasm consisted of interweaving fascicles of minimally atypical spindle cells with slender nuclei and scant cytoplasm. Positive immunohistochemistry for vimentin along with nonreactivity of tumor cells for keratin, S100 protein, desmin, alpha-smooth muscle actin, and CD34 supported the the diagnosis. The diagnosis was later confirmed by histologic and ultrastructural findings following lobectomy. A meticulous clinical search for a possible primary neoplasm elsewhere was unsuccessful, and lung was established as the primary site. Fine-needle aspiration cytology and core biopsy are reliable methods for establishing a diagnosis of fibrosarcoma.

Analysis of false-negative diagnoses on endoscopic brush cytology of biliary and pancreatic duct strictures: the experience at 2 university hospitals.

CONTEXT: Endoscopic brush cytology is a valuable technique for the diagnosis of pancreatobiliary malignancy. Despite its widespread use, the sensitivity of this method has been reported as approximately 50%. The specificity is usually higher than 95%. Few reports have systematically analyzed the reasons for this relatively low sensitivity. OBJECTIVES: To determine the rate and reasons for false-negative diagnoses in endoscopic brushing cytology of biliary and pancreatic ducts based on the results of sensitivity, specificity, accuracy, and positive and negative predictive values. DESIGN: Retrospective analysis of laboratory data and slide review of false-negative cases. SETTING: Two tertiary care state university hospitals. PATIENTS: A total of 183 pancreatobiliary brushing specimens obtained from patients undergoing endoscopic retrograde cholangiopancreatography for biliary or pancreatic duct disease for a 4- to 5-year period. INTERVENTION: Endoscopic retrograde cholangiopancreatography brushings. MAIN OUTCOME MEASURES: Determination of sensitivity, specificity, accuracy, and positive and negative predictive values. Analysis of false-negative results. RESULTS: The sensitivity, specificity, accuracy, and positive and negative predictive values, overall, were 48%, 98%, 79%, 92%, and 76%, respectively. Sampling error was a major cause of false-negative diagnoses (67%), followed by interpretive (17%) and technical errors (17%). CONCLUSIONS: Improvements in sensitivity and diagnostic accuracy for cancer of the pancreatobiliary tract can be achieved by optimizing slide preparatory techniques. Also, enhancement of the cytologist's diagnostic skills enables the identification of the morphologic features of premalignant lesions. Repeat brushings are indicated for suspicious or negative results not consistent with the clinical or radiologic findings.

Cytomorphology of gastrointestinal stromal tumor: diagnostic role of aspiration cytology, core biopsy, and immunochemistry.

Gastrointestinal stromal tumors (GISTs) comprise a heterogeneous group of neoplasms of the gastrointestinal tract previously referred to as leiomyomas, leiomyosarcomas, or schwannomas. GISTs derive from the interstitial cell of Cajal and, in addition to variable expression of smooth muscle and neural markers, they characteristically express CD34 and CD117. To our knowledge, the cytologic appearance of gastric neoplasms designated as GISTs has never been reported. We illustrate the fine-needle aspiration (FNA) cytology findings of a gastric stromal tumor having spindle cells with delicate cytoplasm and prominent nuclear palisading. Consistent core biopsy and immunochemistry findings further supported the diagnosis of GIST. Pathologic evaluation of the resected tumor confirmed the cytologic diagnosis. In the appropriate clinical and radiologic setting, a confident diagnosis of GIST can be established by FNA cytology and core biopsy. The roles of immunochemical stains and other ancillary techniques in reaching the correct diagnosis are addressed.

Fine-needle aspiration cytology and core biopsy of malignant peripheral nerve sheath tumor of the uterus: a case report.

Malignant peripheral nerve sheath tumor (MPNST) is an uncommon mesenchymal neoplasm of neural origin. MPNST arising in the uterus is extremely rare. Its histologic appearance on this anatomical location has been only rarely reported. A 62-yr-old woman with a previous history of partial hysterectomy presented with a large pelvic mass in the uterine stump. Fine-needle aspiration (FNA) and core biopsy were obtained under ultrasonographic guidance, and the diagnosis of MPNST was established. The cytologic and histologic findings were consistent with a spindle-cell neoplasm suggestive of MPNST. The tumor cells were focally positive for S-100 protein immunostain, thus providing further support for the neoplasm's nerve sheath differentiation. The patient had no history of von Recklinghausen's disease. Resection of the mass confirmed the diagnosis of MPNST. To our knowledge, the FNA cytology of MPNST in this unusual location has not been previously reported. FNA cytology, along with core biopsy and immunochemistry, is a reliable tool in the diagnosis of MPNST.

Microcystic adenoma of the pancreas: cytologic appearance on percutaneous and endoscopic ultrasound-guided fine-needle aspiration: report of a case.

Microcystic adenoma is an uncommon neoplasm of the pancreas usually affecting older people. Its histologic features have been well characterized. The cytologic appearance of this tumor has been described only rarely, however, Microcystic adenomas may enlarge considerably and often produce symptoms related to their compression to adjacent anatomic structures. The fact that this neoplasm is almost always benign indicates the need for accurate preoperative diagnosis to differentiate it from other, more common, malignant or potentially malignant tumors of the pancreas. We present a case of pancreatic microcystic adenoma initially diagnosed by percutaneous image-guided fine-needle aspiration cytologic examination and core biopsy and further evaluated by endoscopic ultrasound-guided fine-needle aspiration on follow-up. This case report illustrates that microcystic adenoma of the pancreas can be accurately diagnosed by aspiration cytology. Fine-needle aspiration--percutaneous, guided by computerized tomography, or endoscopically guided by ultrasonography--constitutes a reliable and cost-efficient diagnostic tool associated with minimal trauma to the patient.

Diagnosis of fibromatosis colli by fine-needle aspiration.

Fibromatosis colli is a benign disorder presenting as a neck mass in neonates and older children. The differential diagnosis includes malignancies such as rhabdomyosarcoma. Neck masses in ten infants, discovered between the second and sixth week of age, were evaluated by fine-needle aspiration (FNA). The male to female ratio was 7:3. In 8 patients there was good obstetrical history. Six of the 8 patients had a difficult delivery, as indicated by breech presentation or the need for forceps. Diagnostic aspirations were performed between the second to ninth week of age. The major cytologic finding was benign spindle fibroblasts, usually arrayed in clusters. The cells possessed plump, ovoid nuclei. There were also multinucleated cells consistent with degenerating skeletal muscle fibers. Only one case demonstrated significant inflammation. FNA can provide a rapid and reliable diagnosis in fibromatosis colli. There is support for the idea that in this setting, the disorder is related to perinatal muscular trauma.

Leiomyosarcoma metastatic to the orbit: diagnosis of fine-needle aspiration.

A 47-yr-old man with history of metastatic low-grade rectal leiomyosarcoma presented with progressive protrusion of his left eye due to an enlarging orbital mass. The differential diagnosis included tumor metastasis or orbital infection due to an unknown infectious agent. Diagnostic fine-needle aspiration (FNA) of the orbit was performed on an urgent basis to institute proper therapy and to save the patient's eyesight. Cytomorphologic examination of the material demonstrated a spindle-cell neoplasm consistent with metastatic leiomyosarcoma. It is a rare event for leiomyosarcoma to occur in the orbit. On our review of the literature, the cytology of primary orbital leiomyosarcoma on FNA has only been reported once. To our knowledge, this is the first report of the FNA cytomorphology of metastatic leiomyosarcoma to the orbit.

Olfactory neuroblastoma (esthesioneuroblastoma): appearance on fine-needle aspiration: report of a case.

Small round-cell tumors can arise from several anatomic sites in children and adults, and their primary diagnosis and clinical course often present challenges to physicians. We present a case of a rare adult-onset round-cell tumor, esthesioneuroblastoma, of nasal epithelial origin, which spread into the brain and subsequently to cervical lymph nodes. The report describes how fine-needle aspiration cytology identified the metastatic spread and contributed to its clinical management. The use of ancillary procedures in differential diagnosis of small round-cell tumors is reviewed.

Immunocytochemistry controls using cell culture.

A continuing problem in cytology laboratories is the lack of adequate control material for immunocytochemical testing. Usual control procedures involve testing paraffin-embedded control materials along with the patient specimens. These control materials are fundamentally unlike cytologic preparations. We have developed a method to make control preparations for immunocytochemical analysis using cultured anaplastic cells with known antigenic features from commercial sources. Cell lines included melanoma, rhabdomyosarcoma, T-cell leukemia, and squamous-cell carcinoma. Modified Saccomano and acetone fixation coupled with the cytospin technique enabled good-quality preparations. Cell lines were tested with antibodies for HMB-45, actin, leukocyte common antigen (LCA) and cytokeratin, which avidin-biotin immunoperoxidase and diaminobenzidine (DAB) as chromogens. Our final preparations were easily interpretable with excellent morphologic preservation of cellular detail. Cultured cells provide a superior method for preparing almost unlimited numbers of control slides for immunocytochemistry for laboratories with access to a tissue culture facility.

Diagnosis of recurrent uterine carcinosarcoma by fine-needle aspiration cytology: report of a case.

Uterine carcinosarcomas are uncommon, aggressive neoplasms usually afflicting postmenopausal women. Histologically, they are characterized by the presence of both malignant epithelial and stromal cells. The latter may be either homologous or heterologous in nature. The cytologic diagnosis of carcinosarcoma via fine-needle aspiration (FNA) was previously described for primary tumors arising in the parotid gland, breast, lung, and ovary. Although the diagnosis of uterine carcinosarcoma via cervicovaginal, endometrial, and peritoneal fluid cytology has been described, the FNA cytology diagnosis of recurrent uterine carcinosarcoma has only been rarely described. We present a case of recurrent uterine carcinosarcoma in a 59-yr-old woman, diagnosed by ultrasound-guided FNA cytology. Cytologic smears showed a biphasic neoplasm consisting of both malignant columnar epithelial and spindle cells, in a background of tumor diathesis. This case illustrates the diagnostic utility of aspiration cytology in the investigation of recurrent carcinosarcoma in clinically suspicious lesions arising postsurgery.

Fine-needle aspiration cytology of hemangiopericytoma: report of two cases.

The fine-needle aspiration biopsy (FNAB) findings in two cases of hemangiopericytoma (HP), arising in the parotid gland and on the inner chest wall, respectively, are reported. Smear preparations in each case showed cytologic features of an undifferentiated spindle-cell neoplasm, whereas a core needle biopsy specimen of the chest wall mass showed a spindle-cell tumor with a "staghorn-like" arrangement of endothelium-lined vascular channels. Immunostains performed on this core biopsy, and on the surgical resection specimens in both cases, showed positive staining of tumor cells for vimentin and CD34, with negative staining for a variety of smooth muscle, epithelial, neural, and neuroendocrine markers. Electron microscopy performed in one case further supported the diagnosis of HP. With adequate sampling and appropriate use of ancillary studies, a diagnosis of HP can be reliably suggested on the basis of FNAB and core biopsy of a soft-tissue mass.

Multidisciplinary approach to deep-seated lesions requiring radiologically-guided fine-needle aspiration.

Fine-needle aspiration (FNA) is a diagnostic modality that continues to improve in accuracy as training and experience accumulate. With increasing operator expertise and improved localization techniques, greater numbers of patients are able to benefit from FNAs performed on sites that are otherwise difficult or dangerous to reach by conventional surgery. We present a retrospective review of a 2-yr experience with radiologically-guided deep-seated FNA. In 115 cases involving transthoracic and transabdominal sites, we achieved the following overall figures: 91.9% sensitivity, 100% specificity, 93.9% diagnostic accuracy, 100% positive predictive value, and 80.6% negative predictive value. Our results are compared to those in other series. When properly applied, FNA of deep-seated lesions through image guidance is equivalent to tissue diagnosis obtained by laparotomy or surgical procedures. The benefits of FNA with or without core biopsy vs. scalpel biopsy are readily apparent when one considers the morbidity, cost, turnaround time, and trauma to the patient.

Fine needle aspiration cytology of fibrous dysplasia: a case report.

BACKGROUND: Fibrous dysplasia (FD) is a benign disorder of bone consisting of intramedullary proliferation of fibrous tissue and irregularly distributed, poorly developed bone. Although tumorlike in appearance, FD is probably a condition resulting from failure of maturation from woven to lamellar bone. The histology of FD has been well characterized since Lichtenstein first reported it, in 1938; however, the cytologic appearance has been described only rarely. To our knowledge, this is the first case report of fine needle aspiration (FNA) cytomorphology of FD. CASE: A 30-year-old female with breast carcinoma, diagnosed a month earlier, underwent computed tomography-guided FNA of a rib lesion radiologically thought to represent FD, although metastatic cancer could not be excluded. The smears contained blood, occasional osteoclastic multinucleated giant cells and frequent C-shaped fibrillary structures with dark central areas and lighter peripheries, representing woven bone. The cytologic/radiologic impression of FD was confirmed histologically. CONCLUSION: FNA cytodiagnosis of FD is possible in the setting of consistent clinical and radiologic findings.

FNAC in the diagnosis of recurrent dermatofibrosarcoma protuberans of the forehead. A case report.

BACKGROUND: Dermatofibrosarcoma protuberans is a rare cutaneous soft tissue tumor of intermediate malignant potential with a characteristic tendency for recurrence. Metastases are unusual. This tumor usually occurs in the trunk and extremities and, infrequently, on the face and scalp. Its cytologic appearance on fine needle aspiration has only been rarely reported. It is characterized by numerous fibroblastlike cells that arrange as single cells or in clusters of spindle cells arrayed in a storiform pattern. CASE: A 42-year-old male presented with a one-year history of an enlarging left forehead mass (lateral brow) that was adjacent to an old surgical scar. Fine needle aspiration revealed a low grade spindle cell neoplasm morphologically identical to a dermatofibrosarcoma protuberans excised 15 years earlier, indicating tumor recurrence. CONCLUSION: Distinguishing dermatofibrosarcoma protuberans from other spindle cell tumors and fibrohistiocytic lesions may pose significant challenges to the pathologist. However, in the appropriate clinical setting and applying strict diagnostic criteria, fine needle aspiration cytology is a reliable tool in establishing the diagnosis of this neoplasm.

Fine needle aspiration cytology and core biopsy in the diagnosis of alveolar soft part sarcoma presenting with lung metastases. A case report.

BACKGROUND: Alveolar soft part sarcoma is a rare soft tissue tumor of uncertain origin usually affecting young adults. This neoplasm has early metastatic potential. Its cytologic features, particularly when presenting with metastases, have rarely been described. CASE: A 23-year-old male presented with shortness of breath and scapular pain. Routine chest roentgenograms revealed multiple lung nodules. Malignancy was established by percutaneous fluoroscopically guided fine needle aspiration on a lung nodule. Possible metastatic alveolar soft part sarcoma was suggested by cytology among few considerations in the differential diagnosis. Alveolar soft part sarcoma was confirmed by lung core biopsy and further supported by immunohistochemistry and electron microscopy. Tumor cells expressed muscle-specific actin and myoglobin, and contained diastase-resistant inclusions with periodic acid-Schiff stain. Ultrastructurally, peculiar, elongated intracytoplasmic crystalline bodies typical of this neoplasm were identified. A meticulous clinical search led to finding the primary tumor deeply located in the right posterior thigh. CONCLUSION: Aspiration cytology is a reliable, cost-efficient technique in the diagnostic workup of masses suspicious for malignancy.

Diagnosis of recurrent desmoplastic small round cell tumor by fine needle aspiration. A case report.

BACKGROUND: Desmoplastic small round cell tumor (DSRCT) is a recently described neoplasm characterized by aggressive biology, occurrence in body cavities, expression of antigens from multiple cell lineages and a specific translocation between chromosomes 11 and 22. Most of the published information on this neoplasm is histologic. The case presented here enabled presentation of the cytomorphologic and immunocytochemical features of aspirated cytologic material obtained from this unique tumor. CASE: The cytologic, histologic, radiologic and clinical features of a DSRCT from a 17-year-old patient are presented. Although the initial diagnosis in this case was made on histology, recurrence was proven by fine needle aspiration biopsy (FNAB). CONCLUSION: The presence of sheets or clusters of small round malignant cells, associated with shards of dense fibroconnective tissue, in FNAB should lead the cytologist to consider the diagnosis of DSRCT.

Primary empty sella syndrome in childhood: association with precocious puberty.

Primary empty sella syndrome has been considered an infrequent finding in childhood. One hundred and twelve cases have been reported in children ages 0.7 to 18 years. The frequency of primary empty sella ranged from 1% to 58%. Endocrine abnormalities were described in nearly all children while visual abnormalities were noted in only 6%. Growth hormone deficiency was the single most common hormonal dysfunction noted in children with primary empty sella. Precocious puberty has been rarely reported in association with primary empty sella. We report the case of a 7-1/2 year old girl with gonadotropin dependent central precocious puberty and a partially empty sella who had no other hypothalamic-pituitary dysfunction. We suggest that pubertal abnormalities be included among the endocrine disorders potentially associated with the primary empty sella syndrome.