Expression of monocarboxylate transporter MCT1 in normal and neoplastic human CNS tissues.

Expression of monocarboxylate transporter MCT1 was studied in archival tissues from human CNS using antibodies to the carboxyl-terminal end of MCT1. Sections of neocortex, hippocampus and cerebellum of brains from 10 adult autopsy patients who died from other than CNS disease, and from archival surgical biopsy specimens of 83 primary CNS and eight non-CNS tumors were studied. MCT1 immunoreactivity was present in microvessels and, ependymocytes of normal CNS tissues similar to that reported for MCT1 expression in rat brains. MCT1 immunoreactivity was strongest in ependymomas, hemangioblastomas and high grade glial neoplasms, and weakest in low grade gliomas. Increased MCT1 expression in high grade glial neoplasms may provide a potential therapeutic target for treatment of some CNS neoplasms.

Changes in blood flow in locally heated intestine of rats.

Male Fischer rats were surgically castrated through a lower midline incision and a 5-8 cm long segment of small intestine was fixed to the interior of the right scrotum. Two weeks after the surgery, the herniated intestine was heated by immersing the scrotum into a water bath at different temperatures and the blood flow in the intestine was measured with the radioactive microsphere method. The blood flow in the herniated intestine increased 1.5-2.0 times when the scrotum was heated with 42.5 and 43.5 degrees C water baths for 60-90 min, but began to decrease when heated longer, although the blood flow after heating for 120 min at these temperatures was still slightly larger than the blood flow before heating. Upon heating the scrotum with 44.5 degrees C water bath, the blood flow in the herniated intestine increased to 3-fold of control by 90 min and then rapidly recessed. Massive histological damage was observed 24 h after heating with 44.5 degrees C water bath for 60 min. The blood flow in the intestine measured 1 day after 60 min heating with 43.5 degrees C and 44.5 degrees C water bath was found to be only slightly decreased. Given the relatively small decrease in blood flow, the severe damage in the intestine 24 h after heating may be attributed to direct damage to parenchymal cells.

Intra-abdominal desmoplastic small round cell tumor: immunohistochemical evidence for up-regulation of autocrine and paracrine growth factors.

Desmoplastic small round cell tumors (DSRCT) are highly aggressive tumors typically involving the serosal surfaces of the peritoneum. Patients often present with abdominal pain, an abdominal mass, ascites or signs of intestinal obstruction. Cytogenetic and molecular studies have identified a characteristic t(11;22)(p13;q12) translocation within the tumor cells. The fused gene product apparently aligns the NH2-terminal domain (NTD) of the EWS gene to the zinc finger DNA-binding domain of the WT1 gene. This product could lead to loss of the tumor suppressor effect of the WT1 gene as well as to an increase in EWS driven expression of growth factors normally repressed by WT1. We investigated this latter possibility by performing immunohistochemical studies on formalin fixed tissue from 10 cases of DSRCT and five Wilms' tumors using antibodies to insulin-like growth factor (IGF)-II, the latency associated peptide of transforming growth factor (TGF)-beta1, platelet-derived growth factor (PDGF)-AB chain and PDGF-alpha receptor, respectively. In general, tumor cells were strongly positive for these growth factors in DSRCT, while stromal cells were negative for IGF-II and positive for the other growth factors in parallel with the tumor cells. Wilms' tumor cells were essentially negative for PDGF-AB chains, but positive for IGF-II, and the latency associated peptide of TGF-beta1 and variably positive for PDGF-alpha receptor. These findings support the proposed molecular mechanism of tumorigenesis for DSRCT and may help explain this tumor's poor prognosis.

Intra-abdominal desmoplastic small round cell tumor: immunohistochemical evidence for up-regulation of autocrine and paracrine growth factors.

Desmoplastic small round cell tumors (DSRCT) are highly aggressive tumors typically involving the serosal surfaces of the peritoneum. Patients often present with abdominal pain, an abdominal mass, ascites or signs of intestinal obstruction. Cytogenetic and molecular studies have identified a characteristic t(11;22)(p13;q12) translocation within the tumor cells. The fused gene product apparently aligns the NH2-terminal domain (NTD) of the EWS gene to the zinc finger DNA-binding domain of the WT1 gene. This product could lead to loss of the tumor suppressor effect of the WT1 gene as well as to an increase in EWS driven expression of growth factors normally repressed by WT1. We investigated this latter possibility by performing immunohistochemical studies on formalin fixed tissue from 10 cases of DSRCT and five Wilms' tumors using-antibodies to insulin-like growth factor (IGF)-II, the latency associated peptide of transforming growth factor (TGF)-beta 1, platelet-derived growth factor (PDGF)-AB chain and PDGF-alpha receptor, respectively. In general, tumor cells were strongly positive for these growth factors in DSRCT, while stromal cells were negative for IGF-II and positive for the other growth factors in parallel with the tumor cells. Wilms' tumor cells were essentially negative for PDGF-AB chains, but positive for IGF-II, and the latency associated peptide of TGF-beta 1 and variably positive for PDGF-alpha receptor. These findings support the proposed molecular mechanism of tumorigenesis for DSRCT and may help explain this tumor's poor prognosis.

Cryosurgery of dunning AT-1 rat prostate tumor: thermal, biophysical, and viability response at the cellular and tissue level.

This study investigates cryodestruction of the Dunning AT-1 rat prostate tumor at the single cell, tissue slice, and in vivo levels. The thermal history around a 3-mm-diameter cylindrical cryosurgical probe was predicted by solving the bioheat equation in a one-dimensional cylindrical geometry. At various radial positions in the iceball this thermal history was approximated by a constant cooling rate and a final, steady-state temperature (or end-temperature). The predicted cooling rates and end temperatures ranged from > or = 1000 degrees C/min to 5 degrees C/min and -196 degrees C to -20 degrees C, respectively. These cooling rates and end-temperatures were then imposed on single AT-1 cells, AT-1 tissue slices in vitro and AT-1 tumors in vivo. The single cells and tissue slices were frozen by LN2 immersion, copper block slam-freezing, or controlled cooling on a cryomicroscope or a directional solidification stage. LN2 immersion is lethal to AT-1 cells (presumably due to intracellular ice formation), while cooling at 5-100 degrees C/min leaves some viable cells (at end-temperatures ranging between -20 and -40 degrees C). AT-1 tumor slices show extensive intracellular ice formation due to slam cooling, extensive dehydration at 100 degrees C/min, and total dehydration at rates < or = 10 degrees C/min to end temperatures below -10 degrees C. Postfreeze culture and histology of the AT-1 tissue show that extensive intracellular ice formation is lethal, while cellular dehydration and vascular engorgement leave viable cells (at end-temperatures between -20 and -40 degrees C). Based solely on the single cell and in vitro tissue damage achieved by cooling rates and end-temperatures, a sizable portion of a cryosurgically frozen tumor would be expected to survive. However, in vivo cryosurgery performed on AT-1 tumors demonstrated that the tissue was damaged throughout the cryolesion, even at the periphery where the thermal history would be expected to allow single cells and tissue slices to survive in vitro. Taken together, these results suggest that damage mechanisms other than those due to cooling rate and end-temperature may be responsible for the increased cellular destruction at the periphery of the iceball in vivo and that cooling rate is less important than end-temperature in determining cryosurgical damage in AT-1 tumors. Experiments are ongoing to determine if the time held at an end temperature, thawing rate, vascular response, or other mechanisms are primarily responsible for the enhanced destructive capability in vivo.

Outcome of renal transplantation or dialysis in patients with a history of renal cancer.

BACKGROUND: Therapeutic options for patients with bilateral renal cancer or cancer in a solitary kidney are limited to partial nephrectomy or bilateral radical nephrectomy with subsequent renal transplantation or dialysis. The outcome after partial nephrectomy is well documented, but few reports discuss the long-term survival of patients receiving chronic dialysis or after renal transplantation. Information regarding the long-term prognosis for these patients is important when deciding on the appropriate treatment. METHODS: The authors retrospectively evaluated the long-term prognosis of 23 patients who lost renal function because of surgery for renal cell carcinoma or Wilms' tumor between 1970 and 1990. RESULTS: Twelve patients had renal transplantation (Tx group), and 11 had chronic dialysis (DS group). In the Tx group, four patients had Wilms' tumor and eight had renal cell carcinoma (Stage I, 5 patients; Stage II, 2 patients; Stage III, 1 patient). In the DS group, three patients had Wilms' tumor, and eight had renal cell carcinoma (Stage I, 5 patients; Stage III, 2 patients; Stage IV, 1 patient). Unexpectedly, 9 of 11 (82%) patients from the DS group died of cancer, compared with 1 of 12 (8%) patients who had transplantation (P = 0.0133) despite comparable stages of renal cell carcinoma and Wilms' tumor in the two groups. CONCLUSIONS: For patients who have had bilateral nephrectomy or removal of a solitary kidney, the authors recommend waiting at least 12 months, during which time the patient receives dialysis, before proceeding with transplantation if there is no evidence of recurrent tumor.

Effective immunochemotherapy of CALLA+C mu+ human pre-B acute lymphoblastic leukemia in mice with severe combined immunodeficiency using B43 (anti-CD19) pokeweed antiviral protein immunotoxin plus cyclophosphamide.

A highly aggressive human CALLA+C mu+ pre-B acute lymphoblastic leukemia (ALL) cell line (NALM-6-UM1) causes disseminated and invariably fatal leukemia in CB.17 mice with severe combined immunodeficiency (SCID). We used this SCID mouse model of human pre-B ALL to evaluate and compare, in a total of 434 SCID mice, the antileukemic efficacy of B43 (anti-CD19)-pokeweed antiviral protein (PAP) immunotoxin and cyclophosphamide (CPA) as individual reagents and as combined immunochemotherapeutic regimens. B43-PAP plus CPA was superior to either the immunotoxin or drug alone, and combined immunochemotherapy markedly improved the event-free survival (EFS) of SCID mice challenged with NALM-6-UM1 pre-B ALL cells. Notably, 90% to 100% of SCID mice challenged with 1 x 10(6) leukemia cells and then treated with B43-PAP plus CPA combined immunochemotherapy regimens became long-term survivors, a result not achieved with B43-PAP alone or CPA alone. The advantage was particularly evident in mice inoculated with 5 x 10(6) leukemia cells. While neither 15 micrograms B43-PAP (median survival, 58 days) nor 1 mg CPA (median survival, 49 days) resulted in long-term EFS of SCID mice challenged with 5 x 10(6) NALM-6-UM1 pre-B ALL cells, the probability of EFS at 6 months was 50% +/- 16% for SCID mice treated with 15 micrograms B43-PAP plus 1 mg CPA (median survival, greater than 180 days) (P less than .0001). The probability of long-term EFS was only 14% +/- 7% for mice treated with 30 micrograms B43-PAP and 0% +/- 0% for mice treated with 1 mg CPA, but 40% +/- 16% for mice treated with 30 micrograms B43-PAP plus 1 mg CPA (P less than .0001). Similarly, the probability of EFS at 6 months was 40% +/- 16% for mice treated with 2 mg CPA alone, 70% +/- 15% for mice treated with 2 mg CPA plus 15 micrograms B43-PAP, and 70% +/- 15% for mice treated with 2 mg CPA plus 30 micrograms B43-PAP. Ten SCID mice in the B43-PAP plus CPA combined immunochemotherapy arms surviving long term after the inoculation of 5 x 10(6) NALM-6-UM1 pre-B ALL cells were electively killed at 174 to 181 days to assess their leukemia burden. We found no evidence of leukemia in any of the bone marrow specimens by two-color immunofluorescence and multiparameter flow cytometry.(ABSTRACT TRUNCATED AT 400 WORDS)

In vivo efficacy of B43 (anti-CD19)-pokeweed antiviral protein immunotoxin against human pre-B cell acute lymphoblastic leukemia in mice with severe combined immunodeficiency.

A highly aggressive subclone of the human CALLA+C mu+ pre-B acute lymphoblastic leukemia (ALL) cell line NALM-6 (designated NALM-6-UM1) caused disseminated and fatal leukemia in CB.17 mice with severe combined immunodeficiency (SCID). An intravenous challenge with 1 x 10(6) (NALM-6-UM1 cells caused 15 of 27 (56%) SCID mice to become paraplegic at 31 +/- 2 days (median = 33 days) and 27 of 27 (100%) mice to die of disseminated leukemia at 38 +/- 1 days (median = 39 days). We used this SCID mouse model of aggressive human pre-B ALL to evaluate the in vivo antileukemic efficacy of B43 (anti-CD19)-pokeweed antiviral protein (PAP) immunotoxin. A 3-day treatment with nontoxic doses of B43-PAP markedly reduced the incidence of paraplegia and improved event-free survival (EFS) in SCID mice challenged with 1 x 10(6) NALM-6-UM1 pre-B ALL cells, as reflected by significantly higher cumulative proportions of mice free of paraplegia or alive at 1 to 7 months, as compared with phosphate-buffered saline (PBS) treated control mice. The Kaplan-Meier estimates and standard errors of the probability of developing paraplegia after inoculation of 1 x 10(6) NALM-6-UM1 cells was 64% +/- 10% for PBS-treated mice (median time to paraplegia = 37 days) (N = 27), 18% +/- 8% for mice treated with 15 micrograms B43-PAP (5 micrograms/mouse/d x 3 days) (N = 23) and 5% +/- 5% for mice treated with 30 micrograms B43-PAP (10 micrograms/mouse/d x 3 days) (N = 21). While 27 of 27 PBS-treated control SCID mice died of leukemia at 38 +/- 1 days (range = 24 to 54 days), only 16 of 44 B43-PAP-treated mice developed leukemia at 74 +/- 12 days (range = 30 to 182 days), consistent with greater than or equal to 6 logs kill of clonogenic NALM-6-UM1 cells in 64% of SCID mice. The Kaplan-Meier estimates and standard errors of the probability of long-term EFS after inoculation of 1 x 10(6) NALM-6-UM1 cells were 65% +/- 10% for mice treated with 15 micrograms B43-PAP and 60% +/- 11% for mice treated with 30 micrograms B43-PAP with a median survival time of greater than 7 months for both groups. In contrast, neither unconjugated B43 monoclonal antibody nor the anti-T-cell immunotoxin G17.2 (anti-CD4)-PAP decreased the incidence of paraplegia or improved EFS.(ABSTRACT TRUNCATED AT 400 WORDS)

The solid variant of adenoid cystic carcinoma of the cervix.

We studied seven examples of the solid variant of adenoid cystic carcinoma of the uterine cervix in postmenopausal women who presented with vaginal bleeding and a large ulcerated or polypoid cervical mass. The tumors lacked the characteristic cribriform pattern of conventional adenoid cystic carcinoma. The neoplastic cells were small, undifferentiated, or basaloid and grew in cords, nests, trabeculae, and nodules. Foci of squamous cell carcinoma were seen in three tumors and areas of necrosis in four. A characteristic feature was the production of abundant periodic acid-Schiff's procedure (PAS)-positive basement membrane material that was immunoreactive for collagen IV and that in some areas compressed tumor cells. Electron microscopy on three cases showed globules and cylinders of redundant basal lamina. The tumor cells were joined by desmosomes and contained bundles of tonofilaments. Material similar to basement membrane material appeared to be intracytoplasmic in two tumors. No neurosecretory granules or myoepithelial cells were found. Four deaths were tumor related. Two patients are currently alive, but with local recurrence or metastases; another is alive and well 19 months after surgery. We believe that the solid variant of adenoid cystic carcinoma of the cervix is a distinctive neoplasm that should be separated from small cell carcinomas with or without endocrine features, adenoid basal cell carcinoma, and squamous cell carcinoma.

The role of ilioinguinal lymphadenectomy and significance of histological differentiation in treatment of carcinoma of the penis.

We reviewed retrospectively the medical records of 58 patients treated for squamous cell carcinoma of the penis who were followed for more than 3 years or until they died. Tissue sections from all patients were reviewed. Of 15 patients with stage I disease 11 underwent partial penectomy, and 4 underwent partial penectomy and immediate ilioinguinal lymphadenectomy; none died of cancer. Nine patients with stage II and 9 with stage III disease underwent partial or total penectomy and immediate ilioinguinal lymphadenectomy, and 5-year survival was 100 and 75%, respectively. Of 20 patients with clinical stage II disease who did not undergo immediate ilioinguinal lymphadenectomy 18 had metastasis to the groin. Of these 18 patients 12 underwent delayed ilioinguinal lymphadenectomy but only 1 survived more than 5 years. We evaluated the possible significance of the degree of histological differentiation of the primary tumor to the course of the disease. Of the 23 cases of carcinoma in situ or well differentiated disease only 1 became metastatic, while of the 35 cases of moderately to poorly differentiated disease 31 metastasized to the groin. Vascular invasion of cancer cells in the primary tumor was another indicator for poor prognosis.

Sarcomas of the retroperitoneum and genitourinary tract.

A total of 62 patients with retroperitoneal or genitourinary sarcoma was treated at our institutions during the last 46 years. Of the patients 51 were followed for at least 5 years or until they died (median followup 11 years); 5 patients were lost to followup. The most common site was the retroperitoneum. Liposarcoma, leiomyosarcoma and malignant fibrous histiocytoma were the most common tumors (74 per cent). Tumors were completely resected in 42 patients (68 per cent) and incompletely resected in 11, while a biopsy only was performed in 9. Some patients also received adjuvant radiation therapy and/or chemotherapy. There were no long-term survivors among patients with unresectable tumors. Over-all 3 and 5-year survival rates were 68 and 39 per cent, respectively. The histological type of the tumor appeared to have prognostic significance. The highest 5-year survivals were for liposarcoma (70 per cent), malignant fibrous histiocytoma (33 per cent) and leiomyosarcoma (13 per cent). The mean survival for patients after adjuvant radiation therapy or chemotherapy was similar to that after a radical operation alone. The primary cause of treatment failure was local recurrence (45 per cent of the patients), which was detected within 3 years of complete resection in most cases (82 per cent). Complete extirpation that provided adequate margins free of tumor was the most effective initial treatment and provided the best chance for cure.

Wilms tumor and the VATER association.

We describe an infant with the VATER association in whom a Wilms tumor was noted when she was 5 months old. The lower pole tumor arose near the pelvis and grew into an adjacent calix producing a cystic and solid mass with numerous papillary projections resembling sarcoma botryoides. Histopathologically, the tumor was a classical Wilms tumor but it was unusual in that the papillary projections of the tumor were covered by intestinal-like epithelium, which was interpreted as metaplastic urothelium. The margins were free of tumor and the patient is being treated according to the National Wilms Tumor Study Protocol for stage I lesions. She is currently without evidence of recurrence.

Neuropathic arthropathy as a possible cause of failure of a whole joint allograft. A case report.

This report illustrates the fate of a whole joint allograft in a 23-year-old male with chondrosarcoma of the right hip. An extraarticular resection of the right proximal femur and surrounding pelvis was performed. Reconstruction was carried out with a fresh-frozen cadaveric allograft of articulated proximal femur and acetabulum with the capsule intact. Excellent union at the junction of host bone with the allograft was demonstrated roentgenographically 12 months later. Nineteen months after the operation, as weight bearing proceeded, sudden onset of instability of the joint occurred without pain. Collapse of the allograft with partial dissolution of the femoral head and acetabulum were observed roentgenographically. Reconstruction was achieved with a prosthetic implant. The roentgenographic and pathologic features of the allograft are suggestive of neuropathic arthropathy; however, the possibility of allograft rejection cannot be excluded but seems unlikely.

Adrenal myelolipoma: fine-needle aspiration of an asymptomatic retroperitoneal mass.

We report a case of myelolipoma of the adrenal gland diagnosed by ultrasound-guided fine-needle aspiration in a patient with bronchogenic carcinoma who was noted to have a 5-cm adrenal mass on computerized tomography during evaluation for metastatic disease. The cytologic features are characteristic and consist of mature adipocytes and bone marrow elements that are most clearly demonstrated on Wright-stained cytospin material. This case illustrates the importance of fine-needle aspiration in the evaluation of radiologically detected adrenal masses in patients with known malignancies. A cytologic diagnosis of benign or metastatic disease can eliminate the need for formal surgical exploration in selected cases.

Primary adenocarcinoma of urinary bladder. Clinicopathologic study of 16 cases.

The clinicopathologic and immunohistochemical features of 16 pure adenocarcinomas primary in the urinary bladder were reviewed. Only 3 patients were found to have disease confined to the urinary bladder. Of 13 cases with follow-up only 3 are free of disease. Histologically, the tumors were classified as signet ring cell (3), colloid (3), colonic type (5), clear cell (1), and not otherwise specified (NOS, 4). Immunohistochemically, all tumors but one colloid carcinoma were immunoreactive for cytokeratin and epithelial membrane antigen, and most tumors were likewise immunoreactive for carcinoembryonic antigen. Eight cases were immunoreactive for Leu M1 antigen. Prostate specific antigen, S-100 protein, and placental alkaline phosphatase were uniformly negative. No correlation between immunohistochemical profile and histologic type or clinical outcome was found. The utility of immunohistochemistry and other pathologic findings is reviewed.

Adenocarcinoma with neuroendocrine differentiation of the urinary bladder. Clinicopathologic, immunohistochemical, and ultrastructural study.

We describe a primary mixed adenocarcinoma-neuroendocrine carcinoma of the urinary bladder of probable urachal origin. Neuroendocrine differentiation was confirmed by ultrastructural (neurosecretory granules) and immunohistochemical studies (chromogranin and neuron-specific enolase). Two local recurrences and multiple metastases consisted exclusively of the neuroendocrine component. The patient died 30 months after diagnosis with widely metastatic neuroendocrine carcinoma.

The occurrence of sarcomatous components in primary mediastinal germ cell tumors.

The occurrence of a sarcomatous component in germ cell tumors is an uncommon phenomenon; seven cases with such an association are presented. The sarcomatous elements were rhabdomyosarcomatous in four cases, angiosarcomatous in two, and a combination of these two types in one case. Immunohistochemical studies supported the endothelial and skeletal muscle differentiation of the sarcomatous components. All patients were treated surgically, and some received various chemotherapeutic agents and radiation. On follow-up, four patients had died of their disease, one developed recurrence and pulmonary metastases, one was free of disease after 4 years, and one is a recent case. Chemotherapy protocols may need to be altered to include sarcoma-oriented drugs for this particular group of patients.

Neuroendocrine differentiation in müllerian neoplasms. An immunohistochemical study of a "pure" endometrial small-cell carcinoma and a mixed müllerian tumor containing small-cell carcinoma.

Two neoplasms of the endometrium exhibiting histologic features of small cell carcinoma (SCC) were studied immunohistochemically for the presence of antigens indicative of neuroendocrine differentiation. The first case, a pure SCC, was positive for neuron-specific enolase (NSE), Leu-7, and chromogranin. The second case, a mixed müllerian tumor, had an extensive SCC component; the latter element was reactive for NSE and Leu-7. The first patient has had an unexpectedly long survival, while the second patient died with multiple distant metastases, containing only SCC.

Nephroblastoma. A comparative immunocytochemical and lectin-histochemical study.

Nephroblastomas (Wilms' tumors) from a dog, a bird, a pig, and a child were subjected to comparative immunocytochemical and lectin-histochemical analysis along with normal renal tissues from the same animals. Primary rabbit and mouse anti-human antibodies directed at intermediate-filament proteins, neuron-specific enolase, S100 protein, and epithelial membrane antigen were employed, as were biotinylated peanut agglutinin, soybean agglutinin, wheat germ agglutinin, and lectins from Dolichos biflorus and Ulex europaeus. The human neoplasm showed positivity for cytokeratin and epithelial membrane antigen and bound peanut, soybean, and wheat germ agglutinins in epithelial areas. Among the animal tumors, the porcine and canine nephroblastomas showed immunoreactivity for cytokeratin and vimentin in epithelial and blastematous areas, respectively. In addition, they were positive for S100 protein in epithelial foci. All of these results were substantiated by staining patterns in nonhuman kidneys. None of the neoplasms or renal tissues showed reactivity to the other antigens that were assessed. In the porcine tumor, endothelial cells bound D biflorus lectin, and epithelial areas were stained by U europaeus lectin. The avian nephroblastoma bound peanut, soybean, and wheat germ agglutinins, while the canine neoplasm showed no lectin-histochemical reactivity. These data appear to reflect limited immunohistological and histochemical similarities between nephroblastomas of different vertebrates.

Cystosarcoma phyllodes of the prostate. A pathologic and immunohistochemical study.

We treated two patients who had lesions in the prostate with histologic features similar to those of cystosarcoma phyllodes of the breast. In one case, the stroma progressed to a clearly sarcomatous appearance, whereas the other tumor had a cellular stroma that was mitotically inactive. This element was immunoreactive for vimentin and desmin in both cases but was negative for epithelial markers. In contrast, the epithelial component was immunoreactive for prostate-specific antigen and epithelial membrane antigen. Following surgical resection, both patients were well two and three years later, without local recurrence or distant metastasis. The histogenesis of these tumors is unknown.