Activating Gsα mutation in intramuscular myxomas with and without fibrous dysplasia of bone

Activating missense mutations in the Arg 201 codon of the gene encoding the α subunit of Gs, the G protein that stimulates cAMP formation, have been recognized as the cause of many endocrine diseases, McCune-Albright syndrome and isolated fibrous dysplasia of bone. On the other hand, intramuscular myxomas with fibrous dysplasia, so-called Mazabraud’s syndrome, have been sporadically reported, but it has not been confirmed whether intramuscular myxoma, with or without fibrous dysplasia, is associated with the Gsα mutations. We investigated the presence of the Gsα mutations in intramuscular myxomas with or without fibrous dysplasia by a PCR-SSCP assay, using formalin-fixed, paraffin-embedded tissues. In five of the six intramuscular myxomas (three with and two without fibrous dysplasia), point mutations were detected as aberrant bands by SSCP, which were confirmed by a subsequent sequence analysis (three Arg to His and two Arg to Cys). This result suggests that the Gsα mutations are related to tumorigenesis in intramuscular myxoma and that intramuscular myxoma is one of the diseases induced by abnormal Gsα protein. Received: 10 December 1999 / Accepted: 22 February 2000     

Melanocytic Schwa n no ma in the Spinal Canal

A case of melanocytic schwannoma, a rare form of schwannian neoplasm, in the thoracolumbar spinal canal of a 52-year-old man is presented. Histopathologically, the tumor was composed of irregularly interlacing spindle-shaped cells showing cystic degeneration, with occasional pigmented tumor cells. The tumor cells showed a low degree of nuclear pleomorphism without any mitotic figures. These histological features were considered to be consistent with a benign schwannian tumor showing pigmentation. Most of the pigments were considered to be melanin histochemically and immunohistochemically. According to the pathological features of the present tumor and those described previously in the literature, the neoplastic Schwann cells were assumed to have melanogenetic capacity, and the concept of the common neural crest origin of Schwann cells and melanocytes appeared to be demonstrated in the present tumor. Acta Pathol Jpn 41: 685–688, 1991.     

Juxta-articular myxoma and intramuscular myxoma are two distinct entities

Juxta-articular myxoma is a rare myxoid tumor of soft tissue that bears a close histologic resemblance to intramuscular myxoma but is distinguished from the latter by its clinical setting and behavior. Activating missense mutations at the Arg 201 codon of the Gs alpha gene ultimately leading to increased levels of cyclic adenosine monophosphate have been implicated in McCune-Albright syndrome and sporadic fibrous dysplasia of bone. Recently, we have demonstrated that the same Gs alpha mutations occur in intramuscular myxomas associated with fibrous dysplasia of bone (Mazabraud's syndrome) as well as in sporadic intramuscular myxoma. The overlapping histologic appearances of juxta-articular myxoma and intramuscular myxoma prompted us to investigate whether there is a relationship between the two entities. We studied this possibility by looking for Gs alpha mutations in juxta-articular myxoma using polymerase chain reaction (PCR) to amplify appropriate genomic DNA fragments extracted from formalin-fixed, paraffin-embedded specimens of five juxta-articular myxomas, followed by single-strand conformation polymorphism analysis. Using these techniques, no aberrant bands were detected in any of the five juxta-articular myxomas, indicating that they lack Gs alpha mutations. Moreover, DNA sequencing of the PCR products of two JAMs showed no abnormalities. We conclude that juxta-articular myxomas, in contrast to intramuscular myxomas, do not involve Arg 201 mutations of the Gs alpha gene, indicating that they represent distinct entities with different underlying molecular mechanisms.     

Primary Ewing sarcoma/primitive neuroectodermal tumor in the adrenal gland

Primary Ewing sarcoma or primitive neuroectodermal tumor (PNET) of the adrenal gland is extremely rare. We report a case of Ewing sarcoma or PNET of the adrenal in a 48‐year‐old Chinese woman. The patient was hospitalized with left upper quadrant abdominal pain and swelling that had been present for 1 year. Computed tomography (CT) images revealed a circumscribed mass in the left adrenal region measuring 12 cm in its greatest dimension, and the mass was surgically resected. Macroscopically, the mass (13 × 10 × 8 cm³) in the left adrenal gland was encapsulated, soft, appearing grayish white and yellow, and with foci of cystic degeneration, necrosis, and hemorrhage on cross‐sectional. Non‐tumorous adrenal tissue was compressed, but identifiable at the periphery of the specimen. Histologically, compact short spindle and oval tumor cells were arranged in sheets. Tumor cells tested positive for vimentin, CD99, Bcl‐2, NKX2.2, EMA, and CD117, and weakly positive for FLI‐1 on immunohistochemical analysis and showed rearrangement of the EWSR1 on fluorescence in situ hybridization analysis. Post‐adrenalectomy, after being recurrence free for 4.5 years, the patient relapsed and a localized recurrence was detected on a follow‐up CT scan.     

Vascular leiomyosarcoma: Clinicopathology and immunohistochemistry with special reference to a unique smooth muscle phenotype

Vascular leiomyosarcoma (LMS) is the least frequent type of soft‐tissue LMS and has not been fully evaluated immunohistochemically. The aim of the present study was therefore to examine four cases of vascular LMS, paying special attention to the immunohistochemical expression of smooth muscle markers. All the patients were female; two tumors were located within the inferior vena cava, one within the saphenous vein, and one within the external iliac vein. All the tumors displayed well–moderately differentiated smooth muscle morphology. On immunohistochemistry all four vascular LMS were diffusely and strongly reactive to actins, calponin, and h‐caldesmon, whereas desmin was diffusely stained in one tumor, only focally positive in two, and negative in one. The walls of the blood vessels contiguous to the tumors contained desmin‐ and h‐caldesmon‐positive smooth muscle cells in two cases. In contrast, among 43 non‐vascular LMS (20 well–moderately differentiated and 23 poorly differentiated or other types), 38 were variably positive for desmin, whereas 21 were negative for h‐caldesmon. These findings suggest that the vascular LMS displays a distinctive phenotype of smooth muscle differentiation according to histopathogenesis.     

Total anomalous pulmonary vein drainage: report of an autopsy case associated with atresia of the common pulmonary vein and left superior pulmonary vein

We describe the clinicopathological features of a case of total anomalous pulmonary vein drainage (TAPVD) associated with atresia of the common pulmonary vein (ACPV). A male Japanese infant born at 37 weeks of gestation demonstrated apnea and severe respiratory acidosis immediately after delivery. The patient died of hypoxemic respiratory failure 6 days after birth despite the initiation of artificial ventilation and administration of a surfactant. Autopsy showed the bilateral inferior pulmonary veins joined with a blind confluence, representing ACPV, accompanied by atresia of the left superior pulmonary vein. Moreover, the anomalous and small right superior pulmonary vein drained into the superior vena cava, consistent with partial and supracardiac type TAPVD. A histological examination of the lungs exhibited diffuse dilation of the lymphatic channels in the peribronchial, interlobular, hilar and focally, subpleural areas. The channels were lined with flattened endothelium which was immunohistochemically positive for D2-40. These findings conformed to a secondary form of pulmonary lymphangiectasis due to the congenital cardiovascular anomalies, including TAPVD and ACPV. To the authors' knowledge, this is the first case of TAPVD associated with ACPV, atresia of left superior pulmonary vein and pulmonary lymphangiectasis.     

An immunohistochemical and ultrastructural study of syringocystadenoma papilliferum

BACKGROUND: Syringocystadenoma papilliferum is a benign hamartomatous tumour of the skin. The histogenesis of this tumour is still controversial. There have been few reports regarding immunohistochemical investigations using only a limited range of antibodies and ultrastructural studies on this rare tumour. OBJECTIVES: To elucidate the immunohistochemical and ultrastructural properties of this tumour. METHODS: We investigated the immunohistological patterns of 12 different anticytokeratin (CK) antibodies and several other markers in five cases of this tumour, comparing them with the patterns in adult sweat glands. One of these cases was also evaluated ultrastructurally. RESULTS: The luminal columnar cells of the tumour were mostly positive for CK7 and more than 70% were positive for CK19. These cells showed the heterogeneous expression of CK1/5/10/14, CK14 and CK5/8. These patterns were also observed in the luminal cells in the secretory or the ductal portion of the adult sweat glands. The basal cuboidal cells of the tumour almost constantly expressed CK1/5/10/14, CK5/8, CK14 and CK7 (except for one case), similar to the patterns of basal cells in the transitional portion and myoepithelial cells in the sweat glands. However, the basal tumour cells expressed CK19 and vimentin heterogeneously, and alpha-smooth muscle actin focally (three cases). Ultrastructurally, the constituent epithelial cells were mainly divided into three types: luminal cells, basal cells and clear cells. The luminal tumour cells bore features of the secretory or ductal luminal cells of sweat glands, although they were somewhat immature in appearance. The basal tumour cells were fundamentally basaloid in nature. The clear cells were undifferentiated or primitive in appearance, suggesting stem or progenitor cell properties. Transitional forms between the clear cells and the other two cell types were also identified. CONCLUSIONS: The tumour epithelium was composed of several cell types demonstrating various developmental stages from the primitive clear cells to the basal cells demonstrating a tendency to differentiate toward basal cells in the apocrine transitional portion or myoepithelial lineage, or luminal cells toward the ductal or secretory epithelium. These results support the classical concept that syringocystadenoma papilliferum is a hamartomatous tumour that arises from pluripotent cells.