Blunt-ended Nuclei Research Articles

Primary Intra-axial Leiomyosarcoma with Obstructive Hydrocephalus in a Young Dog

A female Chihuahua dog aged 2 months had a 3-week history of progressive neurological signs (abnormal behaviour, disorientation, left-sided circling, and incessant whimpering). Necropsy revealed a primary leiomyosarcoma in the midline of the posterior thalamus with secondary obstructive hydrocephalus of the lateral ventricles. Grossly, an infiltrative, grey-white tumour had partly invaded the third ventricle. Histologically, the tumour formed hypercellular, interlacing bundles of neoplastic spindle cells with blunt-ended nuclei. Neoplastic cells were strongly immunoreactive for vimentin and both muscle-specific and α-smooth muscle actin; MIB-1 immunoreactivity indicated a proliferative index of up to 5%. Leiomyosarcoma should be included in the differential diagnosis for primary brain tumours and hydrocephalus in young dogs.

Leiomyosarcoma of the breast: a pathologic and comparative genomic hybridization study of two cases

Leiomyosarcoma is an extremely rare form of primary breast sarcoma. We present the pathologic and genetic findings of two cases of leiomyosarcoma of the breast. The patients were 44 and 52 years of age and they presented with circumscribed masses of 3.0 and 4.5 cm, (greatest dimension) respectively. Microscopically, the two tumors showed diffuse proliferation of spindle cells with oval and blunt-ended nuclei arranged in short fascicles or bundles. There was moderate cytologic atypia in both cases, and 6 and 12 mitotic figures per 10 high power fields, respectively. No epithelial component was identified. The tumor cells were strongly immunoreactive for markers of smooth-muscle differentiation, including desmin, muscle-specific actin, and smooth-muscle actin. Comparative genomic hybridization analysis showed losses of 10q (two of two cases), 13q (two of two cases), 17p (one of two cases), and gains of 1q (one of two cases) and 17p (one of two cases). The patterns of chromosomal imbalances identified in leiomyosarcoma of the breast are similar to those reported in leiomyosarcoma of soft tissue and uterus and are different from those reported for leiomyoma, indicating that these alterations may be important for development of malignant smooth-muscle tumors regardless of site or organ of origin.

Fine-needle aspiration of leiomyosarcoma: a correlative cytohistopathological study of 96 tumors in 68 patients.

To better define the cytological features of various leiomyosarcoma (LMS) variants, we reviewed the fine-needle aspiration material and the corresponding histologic sections of 96 tumors in 68 patients. Histological variants of LMS were as follows: 80 (83.3%) were of the classical/usual, seven (7.3%) were epithelioid, and nine (9.4%) were myxoid. Review of original cytology reports showed that 23 (24%) tumors were diagnosed as LMS and 69 (71.8%) as other types of malignancies. Two (2.1%) cases were reported as suspicious and two (2.1%) were unsatisfactory. The classical variants of LMS were characterized cytologically by various proportions of spindle-shaped, cohesive, small- or large-sized cells arranged in parallel alignment. Large spindle, round, binucleated, giant cells with intracytoplasmic granulations were frequently seen. Blunt-ended nuclei, intranuclear inclusions and mitotic figures were occasionally seen, as well as stromal fragments. The epithelioid tumors were composed of an admixture of small and large, spindle-shaped and round cells, also arranged in parallel alignment. Tumor cells with granular cytoplasm, blunt-ended nuclei, intranuclear inclusions, mitotic figures, fibrous or myxoid stroma were not observed. The myxoid tumors disclosed large amounts of background myxoid matrix containing large spindle-shaped and giant cells. Entities such as leiomyoma, malignant peripheral nerve sheath tumor, monophasic synovial sarcoma, and malignant fibrous histiocytoma should be considered in the differential diagnosis of LMS of the classical type. Epithelioid leiomyoma may share similar cytological features with epithelioid LMS. The cytological features of the myxoid variant of LMS can be easily confused with other types of benign and malignant mesenchymal tumors depicting degenerative myxoid changes and/or a myxoid matrix component.

Leiomyosarcoma of the head and neck: a clinicopathological study.

The behaviour of leiomyosarcoma is site-related and there are few data on such tumours located in the head and neck. We studied the clinicopathological features of these lesions. Cases diagnosed as leiomyosarcoma of the head and neck were retrieved from the archives of three institutions. Immunohistochemistry was performed and follow-up information was obtained. There were seven men and six women, aged 21-73 years, and lesions involved the neck (n=3), maxilla (n=4), buccal area (n=3), and maxillary sinus, nose, and pharynx (n=1 each). Tumours ranged from 10 to 80 mm. All tumours showed at least focally typical histological features of leiomyosarcoma with perpendicularly arranged fascicles of smooth muscle cells with blunt-ended nuclei, eosinophilic cytoplasm and paranuclear vacuoles. They expressed muscle-specific actin (8/9), smooth muscle actin (7/9), and desmin (10/12). Follow-up information was available on nine patients. All had surgery, with radiation and/or chemotherapy in seven. Three (27%) recurred at 6-24 months; in one case twice. Five (56%) had metastases, including the three with prior recurrences at 1-128 months. Five (including two who received adjuvant therapy) were disease-free at a median of 47 months, one was alive with metastatic disease at 24 months), and three were dead of disease (median 13 months). Head and neck leiomyosarcomas are rare and aggressive neoplasms which metastasize. Adjuvant therapy has limited effect.

Cytoarchitectural Findings in the Diagnosis of Primary Soft Tissue Tumors

To review the major cytologic and architectural criteria in the diagnosis of primary soft tissue tumors, highlighting the importance of clinical correlation and the value of ancillary methods. Given the variety and complexity of clinicopathologic entities, the initial approach is based on pattern analysis. Six basic categories are established as a function of cell shape, stromal characteristics and resemblance to normal tissue. First, in myxoid-rich matrix tumors, special attention should be paid to lipoblasts, ganglion type, stellate cells and metachromatic fibrillar matrix. Second, in round cell tumors the following cytoarchitectural findings are of special interest: atypical rhabdomyoblasts, atypical lipoblasts, neuroblast rosettes, cytoplasmic glycogen, melanin pigment, islets of mature cartilage, hyaline cytoplasmic inclusions and fragments of connective tissue closely associated with round cells. Third, in spindle tumors the most important cytoarchitectural findings are: biphasic cellularity; elongated, buckled or wavy, tapered nuclei; nuclear palisades; straight, elongated, blunt-ended nuclei; melanotic pigment; storiform pattern; tissue fragments with collagen fibers or degenerated elastin; intracytoplasmic hyaline globules; and scattered spindle cells in a background of red blood cells. Fourth, in pleomorphic tumors specific typing is often difficult, if not impossible, since cells display few or no differential features. Fifth, in epithelial like cell tumors the cytologic findings of major diagnostic interest are: melanin deposits, crystalline inclusions, intracytoplasmic lumina, anisonucleosis and nuclear cytoplasmic inclusions. Last, in maturelike cell tumors, the architectural pattern resembles that of mature tissues. Although cytologic analysis of primary soft tissue tumors is hampered by the paucity of diagnostic findings, the establishment of clinicocytologic correlations, taking into account architectural patterns, cytologic details and clinical characteristics of the lesion, allows precise diagnosis of a significant number of tumors. Application of new techniques (immunocytochemistry, electron microscopy and cytogenetics) to cytologic aspirates has prompted a substantial reduction in the number of doubtful clinicocytologic diagnoses and considerably broadened the diagnostic spectrum.

A distinctive myointimal proliferation ('myointimoma') involving the corpus spongiosum of the glans penis: a clinicopathologic and immunohistochemical analysis of 10 cases.

This study details the clinicopathologic and immunohistochemical features associated with 10 cases of a distinctive myointimal proliferation involving the corpus spongiosum of the glans penis. Patients ranged in age from 2 to 61 years old (mean age, 29 yrs) and presented with a mass that varied in size from 0.5 to 1.9 cm in greatest dimension. The process was said to be present from 4 days to more than 6 months before surgical intervention. In each case, microscopic examination revealed almost identical histology. There was a prominent, often occlusive, fibrointimal proliferation with plexiform architecture involving the vasculature of the corpus spongiosum. The proliferation consisted of stellate-shaped and spindled cells embedded in abundant fibromyxoid matrix. Occasional lesional cells had well-developed myoid characteristics with moderately abundant eosinophilic cytoplasm, blunt-ended nuclei, and juxtanuclear vacuoles. Foci with degenerative changes, including "ghost cell" morphology, were also present. The myointimal process was extensively immunoreactive for alpha-smooth muscle actin, muscle-specific actin (HHF-35), and calponin, but it was minimally reactive for the D33 and D-ER-11 desmin clones. In contrast, native vascular smooth muscle encompassing the proliferation was strongly immunoreactive for all five markers. The myointimal cells were nonreactive for CD34, S-100 protein, and keratin. Factor VIIIrAg, CD31, and CD34 highlighted intact endothelial cells lining suboccluded vessels, scattered capillaries that penetrated the proliferation, and the normal uninvolved vasculature. The examined specimens were punch, incisional, or excisional biopsies, and in each instance, the process microscopically extended to the tissue margin. Follow-up data are available for 8 cases (median follow-up interval, 5 yrs 8 mos): one incompletely excised lesion with 6 months follow-up is stable but persistent, one lesion with 10 years follow-up regressed spontaneously after a punch biopsy, and the remaining six lesions have not recurred. A differential diagnosis of myofibroma, late-stage intravascular (nodular) fasciitis, vascular leiomyoma, and plexiform fibrohistiocytic tumor is discussed.

Leiomyosarcoma of the Gallbladder: A Case Report and Review of the Literature

Primary sarcoma of the gallbladder is an extremely rare neoplasm that was first described in detail by Landsteiner in 1904 (1). In 1982 Willen & Willen (2) published a comprehensive review on primary gallbladder sarcomas and reported a total of 124 cases, 16 of which were reported as leiomyosarcoma. Since then, only a handful of cases of primary gallbladder sarcomas have been reported in the English literature (3–6). We therefore add to this rare type of neoplasm another case report of primary leiomyosarcoma of the gallbladder. Case report. A 67-year-old Caucasian male was admitted to our surgical service with a history of severe right upper quadrant (RUQ) pain, jaundice and shock. Past history was significant for gallbladder disease (non-functioning gallbladder). Physical examination revealed an acutely ill, deeply jaundiced elderly man with a diffuse tender mass, 7 cm×7 cm, occupying the whole RUQ. Rectal examination revealed black tarry stools. Examination of other systems failed to reveal any abnormality. Laboratory workup showed a decreased hemoglobin and hematocrit and an elevated bilirubin and alkaline phosphatase confirming the clinical suspicion of obstructive jaundice. Ultrasound scan of the liver revealed a mass in the right lobe of the liver and a liver scan disclosed a 7 cm oval, cold, solid area in the region of the porta hepatis. The diagnosis of hepatobiliary malignancy was entertained and the patient was prepared for exploratory laparotomy. At laparotomy, a markedly inflamed gallbladder containing multiple stones was found embedded in the omentum and neighboring jejunum. Furthermore, the patient had a mass arising from the porta hepatis, representing either metastasis or an extension of the primary tumor. This was causing external compression of the common hepatic duct leading to a collapsed distal common bile duct. The remaining abdominal organs were normal to palpation. A palliative cholecystectomy and a choledochostomy with insertion of a T-tube were performed. Postoperatively, the patient’s pain and jaundice improved and he was discharged 12 days later to the referring hospital. The patient died 8 days later of advanced metastatic disease. Histopathogical findings. Macroscopic appearance. The gallbladder measured 9×4×3 cm and contained numerous, multifaceted calculi. The external surface was irregular with multiple fibrous adhesions and an irregular mass on one side measuring 2×2×1.5 cm, was present, extending into the lumen. Microscopic examination revealed a malignant mass extending from the gallbladder lumen to the serosa. Microscopic appearance. There were sheets and solid nests of tumor cells with abundant necrosis and focal areas of acute and chronic inflammation. Some areas had a vague fascicular pattern (Fig. 1A). The cells had moderate pleomorphism, ranging from round to oval nuclei with abundant cytoplasm to areas which had a spindle-like appearance, blunt-ended nuclei and scant cytoplasm (Fig. 1B). The chromatin was irregularly clumped and inconspicuous nucleoli were present. The original cytochemical stains performed included reticulin, trichrome, phosphotungstic acid hematoxylin (PTAH), and mucin. The reticulin stain revealed clumps of tumor cells surrounded by delicate bands of reticulin; trichrome stain showed that the tumor cells were surrounded by interlacing bands of fibrous tissue; PTAH was negative for crossstriations; and mucin was negative. On the basis of these histological examinations, the diagnosis of grade 4 spindle-cell sarcoma, probably of leiomyosarcoma type, was determined and confirmed by an outside consultation. Immunohistochemical stains. In light of our ability today to give a more definitive classification of sarcomas, immunohistochemical stains were performed on the original paraffin-embedded tissue using the avidin-biotin-peroxidase complex method. Vimentin (DAKO, Santa Barbara, CA) was strongly positive (Fig. 2); alpha smooth muscle actin (Bio Genex, San Ramon, CA) was positive (Fig. 3); and AE1:3 (broad spectrum keratin), (Boehringer Mannheim, Indianapolis, IN) was also positive. The following stains were negative: carcinoembryonic antigen (CEA) (DAKO, Santa Barbara, CA); desmin (DAKO, Santa Barbara, CA); S-100 (Bio Genex, San Ramon, CA); epithelial membrane antigen (EMA), (DAKO, Santa Barbara, CA); and Mak-6 (Triton Diagnostics, Alameda, CA). Based on the histology and immunohistochemistry, the tumor was designated as a high-grade sarcoma arising within smooth muscle (a high-grade leiomyosarcoma). Discussion. Primary sarcoma of the gallbladder is a rare entity with an estimated frequency of 1.4/1000 gallbladder malignancies (2). It occurs more frequently in females than in males by a ratio of 5 to 1 (7) The average age of patients with primary gallbladder sarcomas is 56 years, which is considerably less than the average age of 70 years for gallbladder carcinoma (7) Gallstones and chronic inflammatory changes have been suggested as the promoting factors in the pathogenesis of gallbladder sarcoma, although no proof exists (7–9).

Primary leiomyosarcoma of the maxilla with regional lymph node metastasis: Report of a case and review of the literature

A rare case of oral leiomyosarcoma diagnosed with the aid of immunohistochemical and electron microscopic examinations together with a review of the literature are reported. The patient was a 70-year-old Japanese man. The primary tumor involved the maxillary gingiva and bone and metastasized to the cervical lymph nodes. On histologic examination the tumor showed invasive growth into the maxillary bone. It was composed of interlacing fascicles of spindle-shaped cells with eosinophilic cytoplasm and elongated, blunt-ended nuclei. The tumor formed extensive metastatic foci in the cervical lymph nodes. On immunohistochemical examination most of the tumor cells were positive for desmin, smooth muscle-specific actin, and myosin. The ultrastructural characteristics of the tumor cells were abundant microfilaments, pinocytotic vesicles, and basement membrane formation. The findings were indicative of a tumor demonstrating myogenic differentiation. A review of the literature during the past 50 years disclosed a total of 60 oral leiomyosarcomas, including our case.

Smooth-muscle proliferation in dermatofibromas.

Although a variety of epithelial changes have been associated with dermatofibromas, mesenchymal proliferations induced by dermatofibromas appear to be rare. We report three dermatofibromas that were associated with proliferation of smooth muscle within the adjacent dermis. The lesions ranged from a large, densely cellular dermatofibroma with "monster cells" to a sparsely cellular, fibrous lesion. In all three cases, the smooth muscle could be discerned in hematoxylin- and -eosin-stained sections, because its presence caused an interruption in the pattern of reticular dermal collagen bundles with blunt-ended vesicular nuclei. Well-formed fascicles were apparent in immunoperoxidase-stained sections using antisera to muscle-specific actin (HHF-35) and desmin. The smooth muscle failed to stain with either antisera to S-100 protein or Leu-7, precluding determination of whether it immunophenotypically resembled vascular or pilar smooth muscle. We believe that the smooth-muscle proliferation in our cases was induced by the spindled cells of dermatofibroma, just as epithelial changes in association with dermatofibroma are. We further believe that it is most likely of vascular derivation, based on a previous report of angioleiomyoma arising in a dermatofibroma as well as the continuity of fascicles of smooth muscle with a thick-walled vessel in one of our cases. Less likely explanations include collisions between dermatofibromas and leiomyomas or divergent differentiation in a proliferation arising from primitive mesenchymal cells.

Intranodal Leiomyoma: Another Distinctive Primary Spindle Cell Neoplasm of Lymph Node

Two intranodal spindle cell neoplasms are described that were interpreted as leiomyomas. Both occurred in young men. The first case involved a single peripancreatic lymph node of a patient with acquired immune deficiency syndrome (AIDS) who died of AIDS-related infection. The second case simulated a parotid gland tumor because of its location in an intraparotid lymph node in an otherwise asymptomatic patient. Both neoplasms were composed of interlacing fascicles of spindle cells with blunt-ended nuclei that seemed to arise from the walls of blood vessels. The tumor cells were immunoreactive for muscle-specific actin but were desmin negative. These leiomyomas expand the clinical and morphologic spectrum of primary spindle cell neoplasms of lymph nodes.

上顎洞平滑筋肉腫の一症例

A case of leiomyosarcoma of the right maxillary sinus in a 55 year-old female is reported. The patient did not respond to radiotherapy or chemotherapy and subsequently underwent total-left maxillectomy and orbital exenteration.Histological examination of the resected tumor revealed interlacing bundles and whorls of spindle like-shaped cells with blunt-ended nuclei. Electron-microscopically, myofilaments, pinocytotic vesicles, dense plaque and dense bodies, which characterized smooth muscles, were observed. Periodic examination of the patient for 10 months has not disclosed local recurrence or any distant metastasis.

LEIOMYOSARCOMA OF THE SOFT TISSUE

Leiomyosarcoma of the soft tissues is a well-defined and characteristic entity histologically but correlative cytomorphological studies are lacking. A correlative histological and cytological study of 11 cases is presented. The leiomyosarcomas were characterized histologically by elongated tumour cells arranged in bundles intersecting each other at wide angles. The nuclei were elongated and often blunt-ended, tending to be aligned in tandem-position or in rows. The smears from leiomyosarcoma were poor in tumour cells and most cells were arranged in clusters of strands. The characteristic blunt-ended cells and nuclei of leiomyosarcoma could be identified in the smears and the nuclei were focally arranged in rows and sometimes in parallel. Nuclear atypia permits diagnosis of malignancy, although the atypia was generally not very pronounced. We consider that a knowledge of the corresponding histological features is mandatory for differentiating cytologically between various soft tissue sarcomas, including leiomyosarcomas. Further correlative cytological and histological studies of other soft tissue sarcomas are necessary for a more valid interpretation of the smears from leiomyosarcomas.

A Case of Leiomyosarcoma

A patient, 39-year-old male, first had noticed a small subcutaneous tumor in his calf in 1970. This tumor had been resected twice on May and June in 1976. But the tumor showed a local recurrence and metastases to the regional lymphnodes, which were also removed after the administration of ADR.A distant soft part metastasis, noticed on his back on February in 1977, became small by the effect of chemotherapy with ADR.Histologically, the tumor cells with blunt-ended nuclei in the interlacing cords were high gradely anaplastic. The mitotic rate was elevated (1-5/HPF).Reticulin was usually present and a majority of the fibrosis was parallel with the long axis of the tumor cells.

Primary leiomyosarcoma of the vagina. Light and electron microscopic observations.

Three primary leiomyosarcomas of the vagina in adult women were studied by light and electron microscopy; two of the tumors were well differentiated and one was anaplastic. They were composed of fusiform cells containing elongated, blunt-ended nuclei arranged in irregular bundles which stained red with the Masson's trichrome stain. The ultrastructure of the tumor cells revealed large, irregular nuclei with a tortuous and bizarre contour, particularly in the less-differentiated tumor. The cytoplasm contained numerous thin myofibrils arranged in clusters and irregular bundles. Clumps of mitochondria were conspicuous at the nuclear poles; they exhibited irregular, dilated cristae which seemed to delineate a matrix of increased density. The granular endoplasmic reticulum had dilated cysternae containing finely granular electron-dense material. The cells were loose with poor cohesiveness. However, marginal dense patches in adjacent cytoplasmic extensions were seen in the anaplastic tumor. The periphery of the cells had abundant pinocytotic vesicles in the differentiated tumor; they were very rare in the undifferentiated one. In both, the cells were coated by a basement lamina which appeared fragmented and poorly defined in some areas. In general, the ultrastructure of the cells is comparable to that of smooth muscle tumors in other organs. The ultrastructural identification of the tumor cells is highly valuable for the differential or confirmatory diagnosis of soft tissue tumors of the female genital system.