MALIGNANT NEUROFIBROMA WITH GLANDULAR DIFFERENTIATION (GLANDULAR SCHWANNOMA)

A case of malignant shwannoma is reported with unusual elements in an 89-year-old female. A large mass was located in the subcutaneous tissue of the right lateral chest wall and measured 5 cm in the greatest diameter. Histologically the tumor was composed of neurofibroma and malignant schwannoma with glandular differentiation. Neurofibroma characterized by numerous hyaline neural nodules was located in the peripheral portion of the tumor, whereas malignant schwannoma occupied a large part of the central portion of the tumor. The glandular elements observed in some areas of malignant schwannoma consisted of cuboidal and columnar shaped cells and were arranged in tubular or tubulo-medullary fashion in which rosettes or pseudorosettes were found. Mucicarminophilic material was observed, both in the cytoplasm and in the lumen. Seven reported cases of peripheral nerve tumor with glandular differentiation are reviewed briefly. ACTA PATH. JAP. 29: 597–606, 1979.     

Benign glandular schwannoma.

The vast majority of reported glandular schwannomas, the rarest type of divergent differentiation in nerve sheath neoplasms, have been malignant tumors. We describe a benign glandular schwannoma, less than 1 cm in diameter, that developed in the deep subcutaneous region of the left flank of a 36-year-old woman. The glandular component occurred as a single large cyst with an undulating lining occupying the central one third of the lesion and was lined in large part by a well-oriented, flattened, single cell layer of cuboidal to low columnar cells with a basement membrane. This extremely unusual lesion, apparently the fourth benign instance reported, is important for several reasons: (1) it does not appear to be a result of inclusion of previously postulated dermal adnexal glands; (2) it further establishes the existence of a true benign counterpart of the glandular schwannoma, of which pathologists should be aware; (3) it can be distinguished from the recently reported pseudoglandular schwannoma; and (4) it lends additional support to the concept of a direct metaplastic origin of the epithelial element from the schwannian component because of the focal presence of a maloriented pseudoglandular element.     

MALIGNANT "RITON" TUMOR WITH METASTATIC HEMANGIOPERICYTOMA IN A PATIENT ASSOCIATED WITH VON RECKLINGHAUSEN'S DISEASE

An autopsy case of malignant schwannoma in a 31-year-old female associated with von Recklinghausen's disease with unusual elements is reported. The patient who was diagnosed as von Recklinghausen's disease from a biopsy specimen of a subcutaneous tumor in her shoulder and multiple café au lait spots in her chest and back, complained of gradual increase in pain in her lower abdomen. A large mass measuring about 18 cm in diameter was located in her left retroperitoneum. Malignant schwannoma associated with von Recklinghausen's disease was indicated by the cellularity of the tumor, intersecting bundles of spindle cells, alternating cellular and less cellular myxoid areas in the peripheral portion of the tumor, whereas a large part of the tumor had a hemangiopericytoma-like arrangement with gaping blood vessels. In addition, however, foci of rhabdomyosarcomatous differentiation and of angiosarcomatous components were found in some areas of this tumor. Moreover, intravascular schwannian growth, which was presumably related to von Recklinghausen's disease, was observed in the heart and thyroid. This tumor should be classified as a malignant triton tumor because of the presence of rhabdomyoblasts.     

Malignant "triton" tumor with metastatic hemangiopericytoma in a patient associated with von Recklinghausen's disease

An autopsy case of malignant schwannoma in a 31-year-old female associated with von Recklinghausen's disease with unusual elements is reported. The patient who was diagnosed as von Recklinghausen's disease from a biopsy specimen of a subcutaneous tumor in her shoulder and multiple café au lait spots in her chest and back, complained of gradual increase in pain in her lower abdomen. A large mass measuring about 18 cm in diameter was located in her left retroperitoneum. Malignant schwannoma associated with von Recklinghausen's disease was indicated by the cellularity of the tumor, intersecting bundles of spindle cells, alternating cellular and less cellular myxoid areas in the peripheral portion of the tumor, whereas a large part of the tumor had a hemangiopericytoma-like arrangement with gaping blood vessels. In addition, however, foci of rhabdomyosarcomatous differentiation and of angiosarcomatous components were found in some areas of this tumor. Moreover, intravascular schwannian growth, which was presumably related to von Recklinghausen's disease, was observed in the heart and thyroid. This tumor should be classified as a malignant triton tumor because of the presence of rhabdomyoblasts.     

Malignant peripheral nerve sheath tumor with rhabdomyoblastic differentiation and glandular component

An exceptional case of malignant peripheral nerve sheath tumor with striated muscle differentiation and glandular component is reported, in a 52-year old man. This tumor measured 8 cm in diameter, and was localized in the chest wall, infiltrating the skeletal muscle. The mesenchymal portion of the tumor was composed mostly of spindle cells arranged in interlacing fascicles. Between these fascicles, there were large cells with abundant eosinophilic cytoplasm and clear elongated nucleus. Immunohistochemical study demonstrated cytokeratin, EMA and CEA expression in the glandular component and S100 protein expression in the major portion of the mesenchymal component. The large cells identified as rhabdomyoblasts, expressed desmin, myoglobin, alpha-SR actin and alpha-SM actin. The tumor recurred 5 years after its resection. Histological and immunohistochemical features were identical. We think that positivity of neoplastic striated muscle cells with alpha-SM actin reflects an early differentiation phase of these cells.     

Malignant glandular schwannoma: a case with favourable prognosis

A solitary malignant schwannoma with glandular differentiation occurred in the forearm of a 54-year-old man. The patient displayed no stigmata of von Recklinghausen's neurofibromatosis. He did well after conservative surgery and there are no signs of recurrence 5 years after operation. The rarity of the tumour and the unusually long survival are points of interest. The histogenesis of the glandular component is discussed.     

An unusual case of glandular schwannoma

Glandular differentiation is exceedingly rare in peripheral nerve sheath tumors. In this report, an exceptional case of retroperitoneal glandular schwannoma is described in which the glandular element is markedly atypical, whereas the schwannian component is benign by morphologic analysis. To the best of our knowledge, the biologic behavior for such a lesion is unknown because similar cases have not yet been described in the literature.     

von Recklinghausen's disease associated with somatostatin-rich duodenal carcinoid (somatostatinoma), medullary thyroid carcinoma and diffuse adrenal medullary hyperplasia.

This report describes the concomitant occurrence of a somatostatin-rich duodenal carcinoid, a medullary thyroid carcinoma and a diffuse adrenal medullary hyperplasia in a patient with von Recklinghausen's disease. A 50-year-old Japanese man died from lung metastasis of a malignant schwannoma. In addition to extensive viscero-cutaneous neurofibromatosis, two different types of neuroendocrine tumors were found in the duodenum and thyroid gland at autopsy. The duodenal tumor, which was located in the second portion, showed the histologic appearance of a carcinoid tumor with glandular differentiation and psammoma-bodies. Immunohistochemically the tumor cells were intensely positive for somatostatin. The thyroid tumor was composed of nests of tumor cells arranged in an endocrine pattern, and showed immunoreactivity for calcitonin. A review of the literature revealed no previously reported case of concomitant occurrence of duodenal somatostatinoma and medullary thyroid carcinoma in a single patient with von Recklinghausen's disease. Morphometric analysis of adrenal glands disclosed the presence of diffuse medullary hyperplasia. Thus, the present case exhibited a similarity in some respects with multiple endocrine neoplasia (MEN) syndrome, Type IIa or IIb.     

Von Recklinghausen's Disease Associated with Somatostatin-rich Duodenal Carcinoid (Somatostatinoma), Medullary Thyroid Carcinoma and Diffuse Adrenal Medullary Hyperplasia

This report describes the concomitant occurrence of a somatostatin-rich duodenal carcinoid, a medullary thyroid carcinoma and a diffuse adrenal medullary hyperplasia in a patient with von Recklinghausen's disease. A 50-year-old Japanese man died from lung metastasis of a malignant schwannoma. In addition to extensive viscero-cutaneous neurofibromatosis, two different types of neuroendocrine tumors were found in the duodenum and thyroid gland at autopsy. The duodenal tumor, which was located in the second portion, showed the histologic appearance of a carcinoid tumor with glandular differentiation and psammoma-bodies. Immunohistochemically the tumor cells were intensely positive for somatostatin. The thyroid tumor was composed of nests of tumor cells arranged in an endocrine pattern, and showed immunoreactivity for calcitonin. A review of the literature revealed no previously reported case of concomitant occurrence of duodenal somatostatinoma and medullary thyroid carcinoma in a single patient with von Recklinghausen's disease. Morphometric analysis of adrenal glands disclosed the presence of diffuse medullary hyperplasia. Thus, the present case exhibited a similarity in some respects with multiple endocrine neoplasia (MEN) syndrome, Type Ila or IIb.     

So-called glandular schwannoma: ependymal differentiation in a case

A cervical root tumor in a patient with neurofibromatosis showed a biphasic pattern of spindle and epitheloid cells with prominent "gland" formation, characteristic of the so-called glandular schwannoma. Electron microscopy and histochemistry of the "glands" disclosed features consistent with an ependymal differentiation. It is noted that there is a curious preferential association of ependymal lesions and neurofibromatosis, the pathogenesis of which is not understood.     

Peripheral nerve sheath tumours--a short series with some uncommon variants

Peripheral nerve sheath tumours are rarely malignant (0.001%), such malignant peripheral nerve sheath tumours (MPNST) are more common in upper extremities than in head and neck. Chondroid differentiation in benign peripheral nerve sheath tumours and melanotic schwannoma are very uncommon. In a retrospective analysis of 25 peripheral nerve sheath tumours over a period of two years, we reported two MPNST one of which was in a parapharyngeal location while the other MPNST showed melanotic differentiation. Similar melanotic differentiation was also seen in another benign melanotic schwannoma. Chondroid differentiation in a schwannoma was also observed which is usually documented in MPNST.     

Cytokeratin profile and neuroendocrine cells in the glandular component of cardiac myxoma

Glandular cardiac myxomas are very rare tumors of uncertain histogenesis that display glandular structures within otherwise typical myxomatous tissue. The origin of the glands has been attributed to epithelial differentiation of a totipotent cardiomyogenic precursor cell or to entrapped embryonal rests in the tumor. We studied four cases of glandular myxomas (three sporadic and one familial) to define the immunophenotypic profile of the glandular elements. The glands were either single and located within the myxoma cell islands (three cases) or in groups embedded in the myxomatous matrix. In the latter case, the glands featured villous projections, irregular profile, active inflammation or focal reactive cellular atypia (case 3) and had acidic and neutral mucins (mostly sialomucins). The cytokeratin expression profile (cytokeratin 7 and 20 co-expression) was similar to that of foregut derivatives. Scattered chromogranin-positive neuroendocrine cells were observed in case 3. Our findings indicate that the glandular component in cardiac myxoma is morphologically heterogeneous. In some cases, the scattered glands may derive from a divergent (epithelial) differentiation of myxoma cells; in others, entrapment of embryonic gastrointestinal rests (with mature neuroendocrine and mucous cell populations) could be the case.     

Flat urothelial carcinoma in situ of the bladder with glandular differentiation

We present the clinicopathologic and immunonohistochemical features of 25 cases of flat urothelial carcinoma in situ with glandular differentiation. Previously, cases on this category have been reported as in situ adenocarcinoma (a term not currently preferred). Fourteen of 25 cases had concurrent conventional urothelial carcinoma in situ. Five of the cases were primary carcinoma in situ with glandular differentiation; twenty cases of secondary carcinoma in situ with glandular differentiation were associated with urothelial carcinoma alone (n = 11) or with glandular differentiation (n = 7), discohesive (n = 1) or micropapillary carcinoma (n = 1). The individual tumor cells were columnar. The architectural pattern of the carcinoma in situ with glandular differentiation consisted of 1 or more papillary, flat or cribriform glandular patterns. Univariate statistical analysis showed no survival differences between urothelial carcinoma in situ with glandular differentiation and conventional urothelial carcinoma in situ (log-rank 0.810; P = .368). Carcinoma in situ with glandular differentiation showed high ki-67 index and p53 accumulation, high nuclear and cytoplasmic p16 expression and diffuse PTEN expression, a phenotype that also characterized concurrent conventional carcinoma in situ. MUC5A, MUC2, CK20, and c-erbB2 were positive in all 25 cases of urothelial carcinoma in situ with glandular differentiation, and CDX-2 was present in 19 cases; MUC1, CK7, or 34βE12 was focally present in 21, 19, and 18 cases, respectively. MUC1core was negative in all cases. We concluded that urothelial carcinoma in situ with glandular differentiation is a variant of carcinoma in situ that follows the natural history of conventional urothelial carcinoma in situ. The immunophenotype suggests urothelial origin with the expression of MUC5A and CDX2 as signature for glandular differentiation.     

Malignant schwannoma associated with embryonal rhabdomyoblastic foci in a single tumor

A case of malignant schwannoma associated with rhabdomyoblastic foci is reported. The tumor was composed of two cellular elements. One was malignant schwannoma cells and the other was embryonal rhabdomyoblast within tumor component. We suggested that this rhabdomyoblast might have been derived from ectomesenchym .     

MALIGNANT SCHWANNOMA ASSOCIATED WITH EMBRYONAL RHABDOMYOBLASTIC FOCI IN A SINGLE TUMOR

A case of malignant schwannoma associated with rhabdomyoblastic foci is reported. The tumor was composed of two cellular elements. One was malignant schwannoma cells and the oher was embryonal rhabdomyoblast within tumor component. We suggested that this rhabdomyoblast might have been derived from ectomesenchym.     

Non-neoplastic glandular structures in a benign peripheral nerve sheath tumor

It is a recognized fact that glandular structures sometimes occur in peripheral nerve sheath tumors (PNST). Reports indicate that epithelial potential could be expressed in malignant PNST, while the glands in most benign PNST could be trapped skin adnexa. We present a case of spindle cell tumor with glandular structures. The patient was a 55-year-old man who had a subcutaneous tumor excised. The spindle cell tumor had histological characteristics of neurofibroma. The glandular structures had a pattern of immunohistochemical staining that was similar to that of the secretory coils and excretory ducts of normal eccrine glands. Therefore, the glands were thought to be naturally existing eccrine glands. The glands were completely enclosed within the tumor and not connected to one another; a cluster formation was not observed. The upper portion of tumor included some glands of skin adnexa. The spindle cell tumor may have originated from the nerves distributed around the skin adnexa, and grown to the subcutaneous tissue. The glands may have been left behind rather than have been trapped in the tumor.     

Epstein-Barr virus RNA detection and glandular differentiation in nasopharyngeal carcinoma: report of 2 cases

Most tumors arising in the nasopharynx are either squamous cell carcinoma or so-called undifferentiated carcinoma of the nasopharyngeal type. Primary adenocarcinomas of the nasopharynx are rare, and glandular differentiation in undifferentiated carcinoma of the nasopharyngeal type has not been reported to date. We report 2 cases of undifferentiated carcinoma of the nasopharyngeal type that show distinct glandular differentiation by light microscopy, histochemistry, immunohistochemistry, and ultrastructure. Both tumors showed equal positivity for Epstein-Barr virus latent membrane protein and in situ hybridization for Epstein-Barr virus genome in the undifferentiated areas of the tumor and those featuring glandular differentiation.     

A case of small polypoid esophageal carcinoma with multidirectional differentiation, including neuroendocrine, squamous, ciliated glandular, and sarcomatous components

A small composite esophageal carcinoma measuring 1.5 x 1.4 x 1.0 cm is described. The tumor had a polypoid elevation with a superficial extension. Histologic examination revealed invasion of the submucosal layer and multidirectional differentiation, including neuroendocrine, squamous, ciliated glandular, and sarcomatous components. The neuroendocrine component was strongly positive for chromogranin and formed the bulk of the polypoid tumor. The squamous cell carcinoma exhibited a superficial extension. The adenocarcinoma was located in a small region of the tumor and contained ciliated glandular cells. The spindle cell sarcomatous component, which was positive for alpha-smooth muscle actin and negative for cytokeratin, exhibited no specific mesenchymal differentiation. Each component was found in 60%, 10%, 5%, and 25% of the tumor, respectively. Cases of small composite esophageal carcinoma containing various carcinomatous and sarcomatous components are extremely rare.     

A case of epithelial–myoepithelial carcinoma of the bronchus – A review of reported cases and a comparison with other salivary gland-type carcinomas of the bronchus

We present a case of a polypoid tumor located in the right middle lobe bronchus. The tumor was composed of bi-layered glandular or ductular structures consisting of inner cuboidal cells and outer multipolar cells. Immunohistochemical examinations confirmed epithelial and myoepithelial differentiation in the inner and outer components, respectively. Consequently, the tumor was diagnosed as an epithelial–myoepithelial carcinoma. Epithelial–myoepithelial carcinomas of the bronchus are very rare neoplasms with low-grade malignant potential. To date, including our case, only 27 cases have been reported in the English literature. Here, we review the reported cases and compare them with other salivary gland-type carcinomas regarding clinical, biological, and genetic features.     

Intraneural angiosarcoma and angiosarcoma arising in benign and malignant peripheral nerve sheath tumours: clinicopathological and immunohistochemical analysis of four cases

AIMS: Angiosarcomatous differentiation represents the least common form of heterologous differentiation in malignant peripheral nerve sheath tumours (MPNST), and is seen most frequently in patients with neurofibromatosis type 1. More rarely, it has been reported in patients without stigmata of neurofibromatosis, or in benign nerve sheath tumours and peripheral nerves. This study was undertaken to confirm this rare association. METHODS AND RESULTS: Four cases of angiosarcoma arising in a peripheral nerve, in a long-standing schwannoma and in two MPNST are described. Immunohistochemical studies were performed on paraffin sections with the alkaline phosphatase-antialkaline phosphatase method. An intraneural high-grade epithelioid angiosarcoma arose in the left posterior tibial nerve of a 78-year-old man, a well to moderately differentiated angiosarcoma was seen in an ancient schwannoma of the lateral neck in a 73-year-old women, and an angiosarcoma of varying grades of differentiation developed in a recurrent MPNST in the thigh of 38-year-old man. In addition a high-grade MPNST in the axillary region of a 30-year-old man showed foci of heterologous high-grade angiosarcomatous differentiation. The neural and endothelial lines of differentiation were confirmed in each case by positive immunohistochemical staining for neural and endothelial markers, respectively. In all cases tested, the neural differentiated cells stained immunohistochemically positive for antibodies against vascular endothelial growth factor. CONCLUSIONS: This study confirms the rare association of angiosarcoma arising in peripheral nerves, as well as in benign and malignant peripheral nerve sheath tumours.