Perineurial abnormalities in the spontaneously diabetic dog

OBJECTIVE: The authors describe the salient clinical, radiologic, and histopathologic features of an orbital primitive neuroectodermal tumor in a 28-year-old man. This is an extremely rare tumor of the orbit, previously reported exclusively in children. DESIGN: Case report. INTERVENTION: Excisional biopsy of the tumor en bloc was performed. MAIN OUTCOME MEASURES: Histopathologic examination was performed by standard techniques and immunohistochemical stains on formaldehyde-fixed, paraffin-embedded tumor tissues. RESULTS: Histologic examination of the sections of the tumor showed small, blue, round cells with occasional Homer-Wright rosette formations. The tumor cells stained positively with neuron-specific enolase and vimentin. CONCLUSIONS: This newly recognized, highly unusual peripheral primitive neuroectodermal tumor should be considered in the differential diagnosis of hypercellular, small, round cell tumor of the orbit in adults.     

Fine needle aspiration cytologic findings in malignant small cell tumor of the thoracopulmonary region (Askin tumor)

From 1980 to 1992, five cases of Askin tumor were diagnosed by fine needle aspiration cytology at the Shiraz University Hospitals, Namazi, Faghihi and Beheshti, Iran. All patients were female, their ages ranging between 15 and 22 years. Three of them had a mass on the right side and two on the left side of the chest. Chest roentgenography revealed no bone involvement. Two tumors involved the lungs and pleura. Urinary catecholamine levels were within normal limits. The fine needle aspiration smears revealed many small, round malignant cells with indistinct cytoplasm, a high nuclear/cytoplasmic ratio and prominent, multiple nucleoli. Homer-Wright rosettes were seen frequently. The cells were often arranged in rows simulating rouleaux formation. They were positively stained by periodic acid-Schiff stain. The histologic sections confirmed the cytologic diagnosis of Askin tumor. Four of the patients died within 7-11 months after treatment began.     

An autopsy case of extraskeletal Ewing's sarcoma followed up for 24 years

A long-term (24 years) follow-up case of extraskeletal Ewing's sarcoma is reported. The light microscopic examination showed features hardly indistinguishable from Ewing's sarcoma of the bone, that is, the tumor cells were diffusely arranged and uniform in size and shape, and possessed glycogen in the cytoplasm. Homer-Wright rosettes were found only in the autopsy material. An immunohistochemical study using a neural marker (neuron-specific enolase) demonstrated positive staining in most tumor cells. An ultrastructural study revealed intracytoplasmic glycogen particles and incomplete neural characters as follows: the cytoplasmic processes resembled neural processes without neurosecretory granules, microtubules or neurofilaments. These findings suggest that this case finally acquired an incomplete neural character with repeated recurrence. This tumor was diagnosed extraskeletal Ewing's sarcoma, but in future it may be categorized as primitive neuroectodermal tumor (PNET).     

Pain in the family

A case is reported of atypical glomus tumor occurring in the posterior inferior mediastinum of a 26-year-old woman complaining of severe back pain. The tumor was composed of atypical small, round tumor cells with scattered mitotic figures. In addition to sheet-like, diffuse proliferation of the tumor cells, some areas of the tumor contained small "glomoid" cells arranged in organoid and hemangiopericytomalike patterns. Immunohistochemically, many tumor cells were positive for muscle-type actins and a few cells were focally positive for desmin. Ultrastructural studies revealed smooth muscle features of tumor cells, that is, pinocytotic vesicles, external laminas, dense plaques, and occasional thin filaments with dense bodies. The patient remained well for 5 years and 4 months after the operation without additional radiation and chemotherapy. The tumor was diagnosed as an atypical, or low-grade malignant, glomus tumor morphologically. It seems important to recognize the presence of this type of tumor in sites other than extremities and to differentiate it from other malignant small, round cell tumors.     

Conformational study of a collagen peptide by 1H NMR spectroscopy: observation of the 14N-1H spin-spin coupling of the Arg guanidinium moiety in the triple-helix structure

A 36-month-old girl had a 3-week history of proptosis of the right eye. Computed tomography showed an ill-defined homogeneous mass filling the intraconal space. Histopathologic examination and immunohistochemistry findings of an incisional biopsy specimen were consistent with malignant undifferentiated tumor with rhabdoid features. Despite chemotherapy (a combination of vincristine sulfate and dactinomycin) and radiotherapy, massive orbital recurrence occurred 6 months later and orbital exenteration was performed. The recurrent tumor was composed entirely of pleomorphic epithelial cells with prominent nucleoli and many filamentous cytoplasmic inclusions. Immunohistochemical staining showed positive immunoreactivity for vimentin, cytokeratin, and epithelial membrane antigen, and negative immunoreactivity for muscle-specific antigen, melanoma, neural, and histiocytic markers. Electron microscopy excluded myogenic differentiation and showed that the filamentous cytoplasmic inclusions were composed of whorls of intermediate filaments. Aggressive chemotherapy with a combination of vincristine, doxorubicin, cyclophosphamide, ifosfamide, and etoposide phosphate was continued after exenteration. At 17 months' follow-up, orbital debulking surgery with externalization of the maxillary sinus was performed because of massive tumor recurrence in the right orbit and growth into the maxillary sinus. The child died 23 months after initial diagnosis from tumor invasion into the central nervous system. Extrarenal rhabdoid tumor is a rare orbital mass that carries a poor prognosis.     

Small round and spindle cell sarcoma with neuronal differentiation and oncocyte-like features of the thoracic wall: a case report with histological, immunohistochemical and ultrastructural examinations

A case of small round and spindle cell sarcoma with neuronal differentiation and oncocyte-like features is presented. The tumor was encountered in a 32 year old Japanese woman with an initial presentation of palpable tumor in the left lateral region of the thorax. The resected tumor was a partially well encapsulated whitish medullary one and consisted of small round and spindle tumor cells, together with so-called rhabdoid cells in the small round cell area. Although pseudorosettes were often observed, true rosette formation could not be detected anywhere. Ultrastructurally, despite a histologic variety of tumor cells, most tumor cells possessed numerous mitochondria, some of which occasionally contained abnormal filamentous or crystalloid structures. Various amounts of microfilaments were present in most tumor cells and microtubules were present in a few. A minority of small round cells possessed a small number of neurosecretory granules, especially in short cytoplasmic processes. A positive immunoreaction for neuron specific enolase was found by immunohistochemical examination in several small round tumor cells and for neurofilaments in lesser numbers. Despite the lack of S-100 protein, MB2 was detected in both small round and spindle cells. On the basis of these findings, the tumor of the present case corresponds to malignant peripheral nerve sheath tumor with neuronal differentiation and oncocytic features.     

Peripheral primitive neuroectodermal tumor in parietal pleura]

A 19-year-old woman was admitted to Kushiro city general hospital due to chest pain and dyspnea. Chest radiographs and computed tomographic scan showed a large intrathoracic mass adjacent to the pleura. Angiographs disclosed feeding veins of the tumor arising from lateral thoracic artery. Fine-needle aspiration cytology of the tumor revealed small round cells with a large nuclear/cytoplasmic ratio. Immunocytochemical study demonstrated that the tumor cells were positive for neuron-specific enolase and MIC 2 gene product. The diagnosis was primitive neuroectodermal tumor of the parietal pleura (also known as Askin tumor). Chemotherapy combined with peripheral blood stem cell transplantation reduced the size of the tumor significantly. However, multiple bone metastasis recurred, and the patient died 35 months after the start of therapy.     

Alpha-chain disease in a non-Mediterranean climate. A case report

The clinical, biochemical, immunological and histopathological features in a patient with alpha-chain disease are described. The patient, a 20-year-old Coloured man, presented with severe steatorrhoea, malabsorption, abdominal pain and progressive general deterioration. An heterogeneous abnormal band with IgA immunochemical specificity was detected on electrophoresis of the patient's serum and urine. This protein was identified as free alpha-chain and was present in serum, urine, saliva and jejunal juice. A jejunal mucosal biopsy specimen showed distinctive appearances associated with alpha-chain disease. Bone marrow involvement was found and abnormal lymphoid cells were seen in the circulation together with an increased B lymphocyte population derived from bone marrow. This is the third South African patient with alpha-chain disease to be diagnosed. The patient has shown a partial remission after 12 months' chemotherapy. There was rapid symptomatic response and normalisation of protein parameters which were not paralleled by an objectively discernible response as assessed by haematological examination, intestinal absorption studies and histology of the jejunal mucosa.     

Adrenal pheochromocytoma mimicking small cell carcinoma on fine needle aspiration biopsy. A case report

BACKGROUND: Fine needle aspiration biopsy (FNAB) is a sensitive and specific technique in the diagnosis of adrenal tumors. However, in rare cases the cytomorphologic features may mimic small cell neoplasms. CASE: A 54-year-old male presented with a history of hypertension and left flank pain of recent onset. Abdominal computed tomography (CT) showed a 4-cm mass involving the left adrenal gland. Fine needle aspiration biopsy (FNAB) showed groups of small round cells with hyperchromatic nuclei. The findings were highly suspicious for metastatic small cell carcinoma. Subsequently it was learned that the mass had been noted three years earlier on CT studies but had grown from 2.5 to 4 cm. A chest radiograph was unremarkable. The clinical findings were more in keeping with a primary adrenal tumor. Immunohistochemical staining done retrospectively on the cell block showed positive reactivity for chromogranin and neuron-specific enolase. These findings, correlated with the clinical features, were in keeping with a diagnosis of pheochromocytoma. Left adrenalectomy revealed a pheochromocytoma. CONCLUSION: Adrenal pheochromocytoma should be included in the differential diagnosis of small round cell neoplasms seen on FNAB of the adrenal gland. Immunohistochemistry and clinical findings are helpful in reaching the correct diagnosis.     

Activity of pentamidine-loaded methacrylate nanoparticles against Leishmania infantum in a mouse model

Polyvinylpyrrolidone (PVP), formerly a plasma expander, has continued to be inappropriately used in Taiwan for intravenous injection as a "blood tonic." Five cases of PVP storage disease with cutaneous involvement were studied. Two patients presented with cutaneous eruptions mimicking collagen vascular disease and chronic pigmented purpuric dermatosis. Two other cases were found incidentally: one was with a metastatic tumor and the other in a pemphigus lesion. The fifth case was seen in a blind skin biopsy specimen taken to exclude Niemann-Pick disease after hematologic examination of a bone marrow smear. The latter patient and the patient with a collagen vascularlike disease also had severe anemia and serious orthopedic and neurologic complications due to massive infiltration of PVP-containing cells in the bone marrow with destruction of the bone. Severe irreversible anemia due to PVP storage disease has not been reported before. Three patients admitted having a history of receiving intravenous injection of PVP. The samples obtained from two of them indeed contained 5% PVP as determined by chemical analysis. PVP storage disease can be diagnosed by its histopathologic features. The skin biopsy specimens all showed a variable number of characteristic blue-gray vacuolated cells around blood vessels and adnexal structures with positive tinctorial reactions to mucicarmine, colloidal iron, and alkaline Congo red and negative to periodic acid-Schiff (PAS) and alcian blue. The PVP storage cells were shown to be CD68+ macrophages. The presence of PVP in the skin induced little or no inflammatory reaction. Only the pelvic mass in one patient had a foreign body granuloma formation. Our study showed that systemic parenteral administration of PVP preparation could result in the accumulation of PVP storage cells in the skin, with or without clinical eruptions. The diagnosis of systemic PVP storage disease can be established by performing a skin biopsy for pathologic study. It is important for pathologists and clinicians to be aware of this iatrogenic storage disease to avoid misdiagnosis for hereditary storage disease, osteomyelitis, or signet-ring cell carcinoma. Serious hematologic and orthopedic complications can be caused by repeated massive intravenous injection of PVP. Therefore, PVP preparations should be strictly prohibited for systemic administration.     

Primary small cell carcinoma of the larynx

Small cell carcinoma is a rare tumor of the larynx. We present such a case in a 78-year-old female. The histopathological diagnosis at the time of laryngomicroscopic biopsy was squamous cell carcinoma, upon which basis we initially chose surgical treatment. The surgical specimen, however, revealed small cell carcinoma. Despite the administration of radiotherapy and chemotherapy, the patient died 9 months after initial presentation. We believe that this case illustrates the need for a sufficiently large biopsy specimen in order to arrive at the correct histopathological diagnosis when small cell carcinoma of the larynx is present, and that immunohistochemistry and electron microscopy should be performed to aid the diagnosis.     

The ultrastructure of intermediate type trophoblast cell

Transmission electron microscopy was used to clarify the detailed morphology of the "intermediate type" trophoblast cell in normal and tumor issue. 67 normal placental villi specimen, 10 placental bed specimens and 10 malignant mole, 10 hydatidiform mole, 5 choriocarcinoma specimen (the last three types taken before chemotherapy) were examined. Results showed that the transitional type trophoblasts of the placenta were developed from cytotrophoblasts through differentiation and fusion to syncytiotrophoblasts which showed features of maturation and aging, having features of cytotrophoblast nuclei and syncytiotrophoblast cytoplasm. The transitional trophoblast of placental bed showed similar morphology as that of transitional type cells of villi. The morphology of transitional type cells of villi. The morphology of transitional type cells of trophoblastic tumors had both normal morphology and cellular hyperplasia, atypia and features of tumor ultrastructure. The prominent feature was the high electron density of the granules and polymorphic cysts crowded in villi, demonstrating that the morphology of "intermediate type" trophoblasts in placental and tumor tissue are similar, whereas heterotype cellular morphology is present in varying degrees in tumor tissue.     

Histology, immunohistochemistry, and electron microscopy of small round cell tumors of bone

Small round cell tumors (SRCTs) of the bone make up a family of primary bone sarcomas with morphologically, biologically, and clinically specific features. Among them, Ewing's sarcoma (ES) is the most common entity, but several varieties such as atypical ES, large cell ES, and ES with neuroectodermal differentiation (peripheral primitive neuroectodermal tumor of the bone or neuroepithelioma of the bone) have been identified recently. Histology and electron microscopy together with the variable expression of several epitopes (as shown by immunohistochemistry, mainly HBA/71 [Mic2 antigen]) provide the basis for characterizing the group within the context of neuroectodermal-derived neoplasms. A number of other ES-like tumors with small round cells, mimicking those previously described, have been characterized; Askin's tumor of the thoracopulmonary region will be considered as an ES similar to those already described, but within a particularly anatomic location. On the other hand, the presence of an endothelial appearance within a poorly differentiated neoplasm may be present in some ES-like SRCTs (atypical ES with endothelial features). The differential diagnosis with other sarcomas defined by small round to spindle cell contours might prove difficult. Particular attention must be paid to small cell osteosarcoma and mesenchymal chondrosarcoma. Likewise, "primitive sarcoma of bone" is considered in this study because it is a very rare neoplasm differing from the formerly discussed types; its pluripotentiality provides this tumor a blastemic character and a multiphenotypic expression. Malignant non-Hodgkin's lymphoma is an unusual presentation when primary to the bone, previous to any other anatomic location. Several subtypes have been considered within a histology that encompasses that seen in lymph nodes.     

Disseminated carcinomatosis of the bone marrow occurring 11 years after subtotal gastrectomy for gastric cancer]

A 44-year-old man was admitted to our hospital because of purpura, increased serum alkaline phosphatase, and thrombocytopenia. He had undergone subtotal gastrectomy for gastric cancer 11 years earlier. A biopsy specimen of the bone marrow revealed metastatic mucin-forming, moderately differentiated adenocarcinoma. Because the primary tumor was not detected in any other organ, the gastric cancer the patient was treated for 11 years earlier was suspected as the primary tumor. Microangiopathic hemolytic anemia and disseminated intravascular coagulation developed during the clinical course, and the patient deteriorated despite treatment with anticoagulants. Finally, he died of pulmonary carcinomatous lymphangitis. Autopsy revealed a small number of adenocarcinomatous cells in the lymphoduct of the remaining stomach in spite of its mucosa being intact. We concluded that the bone marrow was infiltrated by cancer cells which originated in the stomach 11 years before. It is unclear why adenocarcinoma cells remained dormant for as long as 11 years in the gastric lymphoduct and bone marrow.     

Expression of P-glycoprotein in high grade osteosarcomas with special emphasis on chondroblastic subtype

The development of chemoresistance is one of the major clinical problems in the therapy of malignant bone tumors in childhood. The expression of membrane-bound P-glycoprotein turned out to be an essential factor in the evidence of resistant tumor cells. To investigate the significance of multidrug resistance in the prognosis of highly malignant osteosarcomas, the immunohistologic expression of P-glycoprotein was investigated in the tumor tissue of 52 patients under special consideration of the histologic subtype. The data were compared with the histologic regression grade in the resection specimen and correlated with clinical data. Formalin-fixed, paraffin-embedded tissue and, additionally, fresh frozen material taken from the primary biopsy were stained using monoclonal antibody JSB1. 29 (55%) of the tumors investigated were P-glycoprotein positive. Considering the response to chemotherapy, no conclusion could be drawn regarding P-glycoprotein expression, regression grade in the resection specimens, and the clinical follow-up. P-glycoprotein was detected in only 52% of the non-responders. A positive reaction was also evidenced in 59% of the patients with high chemosensitivity. A comparison of the histologic subtypes yielded a significant result in the chondroblastic osteosarcomas. 11 of 12 cases showed a strong expression of P-glycoprotein. Most of the cases were non-responders, and using Kaplan-Meier live tables, an unfavorable clinical outcome could be demonstrated. Possibly, chondroblastic tumors have a special position among osteosarcomas because of their differentiation.     

Unusual endocrine presentations of nasopharyngeal carcinoma

BACKGROUND: Nasopharyngeal carcinoma is endemic in Southern China and the majority of patients present with local symptoms due to the tumor. METHODS: This report describes two unusual cases of occult nasopharyngeal carcinoma in which the patients initially presented with endocrine manifestations. RESULTS: The first patient presented with Cushing's syndrome secondary to ectopic adrenocorticotropic hormone (ACTH) production. Nasolaryngoscopy showed a growth in the left nasal fossa and biopsy revealed a poorly differentiated nasopharyngeal carcinoma that exhibited positive immunostaining for ACTH. The second patient presented with a 10-month history of bone pain over both lower limbs. She was normocalcemic but her serum alkaline phosphatase was markedly elevated. A bone biopsy showed both osteoclastic and osteoblastic activity with widespread fibrosis suggestive of Paget's disease. Three months later, she developed third cranial nerve palsy. Computed tomography investigation revealed a soft tissue mass filling the sphenoid and ethmoid sinuses. Biopsy showed a poorly differentiated nasopharyngeal carcinoma. The bone biopsy was reviewed and immunohistochemistry demonstrated the presence of cells positive for the epithelial marker AE1/3 within the fibrous stroma. Radio-labeled in situ hybridization showed that Epstein-Barr virus early RNA was present in these tumor cells and the bone lesions were in fact metastases. CONCLUSIONS: Nasopharyngeal carcinoma can present with rather atypical symptoms that may lead to a delay in diagnosis. Therefore, in high risk populations, it is important to consider nasopharyngeal carcinoma as a possible primary tumor in patients with occult carcinomas.     

Primary round-cell liposarcoma of the bladder

OBJECTIVE: To report a rare case of primary round cell liposarcoma of the urinary bladder. METHODS: A case of primary round cell liposarcoma of the urinary bladder in an 80-year-old female with hematuria is presented. The patient had a large, solid, non-circumscribed bladder tumor of 6.5 cms. The radiological, histological and immunohistochemical findings are discussed. RESULTS: The neoplasm was composed of isolated lipoblasts among numerous small round cells that were positive for S-100 and vimentin, and a high proliferation rate was demonstrated by Ki-67. The patient died 10 months after the histologic diagnosis. CONCLUSION: Primary liposarcoma of the urinary bladder is a very rare tumor with a poor prognosis that usually presents as a large tumor mass.     

Liver metastases from breast cancer 14 years after radical mastectomy; successful treatment with hepatic arterial infusion chemotherapy and systemic endocrine therapy--a case report

The patient was a 73-year-old woman who was admitted to our hospital for epigastric discomfort and body weight loss. She had undergone radical right mastectomy in March 1982. Ultrasonography and computed tomography revealed multiple tumors in the liver. Three of the tumor markers (CA-125, CA 19-9, and CA 15-3) were positive. US-guided fine needle aspiration biopsy of the liver tumor showed small atypical cells with solid cell nests. Immunohistochemical tests revealed estrogen receptor was positive. We diagnosed the patient as recurrent breast cancer metastatic to liver, 14 years postoperatively. The liver tumors were successfully controlled with the combination of intra-arterial infusion chemotherapy (5-fluorouracil, epirubicin, and mitomycin C) along with systemic endocrine therapy (medroxyprogesterone acetate and fadrozole hydrochloride hydrate).     

An autopsy case of cytokeratin 7-positive minute adenocarcinoma of the lung with systemic metastases

We describe a 60-year-old woman with leg pain. Although metastatic bone tumor and atypical cells mimicking signet-ring cells in the bone marrow picture were observed, systemic survey revealed no primary lesion. The patient died two months after admission from systemic progress of the disease. Autopsy revealed a small focus of adenocarcinoma within the right upper lobe of the lung and systemic metastases without any particular changes in the gastrointestinal tract. The tumor cells of the lung were diffusely positive for cytokeratin 7, whereas cytokeratin 20 immunoreactivity was weak and focal, and that supported the lung origin of the present tumor. Moreover, the tumor cells in the bone marrow showed a similar pattern in immunoreactivity. These findings suggest that cytokeratin 7 and cytokeratin 20 immunoreactivity is helpful for the premortem diagnosis of the metastatic tumor of unknown origin.