What's new in nerve sheath tumors.

Peripheral nerve sheath tumors are commonly encountered and frequently pose challenges to the pathologist and the clinician. This review discusses the wide range of entities with an emphasis on new discoveries in the past decade. Clinical, histologic, immunohistochemical, and pathogenetic findings are discussed with an emphasis on clinical implications and differential diagnosis.

Orbital granular cell tumor in a patient with Churg Strauss syndrome: the importance of biopsy.

A 65-year-old woman presented with a long standing, progressive exophthalmos of the right eye. Her medical history was significant for Churg Strauss syndrome, and was treated with immunosuppressive therapy. She had undergone two previous orbital biopsies showing inflammatory reactive lymphoid hyperplasia. A diagnosis of orbital inflammation in Churg-Strauss syndrome was suspected, and the immunosuppressive therapy was increased. Because of the lack of response to therapy, a further biopsy was performed, by lateral orbitotomy approach. Biopsy of the mass revealed a granular cell tumor composed of S-100 positive cells with an acidophilic granular cytoplasm and peripheral lymphocytic infiltration. A granular cell tumor, which is very rare in the orbit, should be considered in the differential diagnosis of orbital tumors, and if suspected, an excisional biopsy must be undertaken. Typical histopathological aspect of the granular cell tumor is characterized by the presence of S-100 positive closely packed polygonal cells with a granular cytoplasm.

Multiple granular cell tumors are an associated feature of LEOPARD syndrome caused by mutation in PTPN11.

We report a patient with a clinical and molecular diagnosis of LEOPARD syndrome (LS) associated with multiple granular cell tumors (MGCT). Bidirectional sequencing of exons 7, 12, and 13 of the PTPN11 gene revealed the T468M missense mutation in exon 12. This mutation has been previously reported in patients with LS. To our knowledge, this is the first report of MGCT associated with molecularly characterized LS and provides the first molecular evidence linking granular cell tumors (GCT) to the Ras/mitogen-activated protein (MAP) kinase pathway. We propose that MGCT can be associated with LS. Analysis of GCT from this case tested negatively for loss of heterozygosity (LOH) at the PTPN11 and NF1 loci and did not show deletions of the PTEN gene. The absence of LOH of PTPN11 supports published functional data that T468M is a dominant-negative mutation.

Expression of calretinin and the alpha-subunit of inhibin in granular cell tumors.

Granular cell tumors (GCTs) typically express S-100 protein, which has been used as a marker in differential diagnosis. Calretinin, a calcium-binding protein related structurally to S-100, and inhibin, a polypeptide hormone secreted primarily by ovarian granulosa cells and testicular Sertoli cells and functioning as an inhibitor for pituitary follicle-stimulating hormone secretion, are potentially useful but not well-evaluated markers for GCTs. We studied 43 cases of GCT with antibodies to calretinin, the inhibin alpha-subunit, and S-100 protein. All tumors were positive for inhibin alpha-subunit and S-100 protein, with 50% or more cells showing moderate to strong staining. Forty tumors (93%) were positive for calretinin, ranging from focal weak to diffuse strong staining. Enhanced staining for calretinin in the tumor cells adjacent to hyperplastic squamous epithelium was observed in 9 of 13 cases showing pseudoepitheliomatous hyperplasia. Calretinin and the inhibin alpha-subunit are useful markers for GCTs. The expression of calretinin, a primarily neuronal protein, in GCTs further supports its neural differentiation or derivation. The elevated calretinin expression in the tumor cells adjacent to the hyperplastic squamous epithelium suggests a role for calretinin in the tumor cells-squamous epithelium interaction.

Tumor de células granulares de la región anal: Presentación de 1 caso / Tumor of granular cells of the anal region. Presentation of 1 case

Se informa un caso de tumor de células granulares (mioblastoma) de la región anal, en una mujer de 54 años de edad que acudió al Hospital Clinicoquirúrgico Docente "Joaquín Albarrán" por "quiste palpable en las márgenes del ano. El tratamiento que se realizó fue la resección local del tumor. Se analizaron los patrones histopatológicos e inmunohistoquímicos, los cuales se correspondieron con los reportados en la literatura médica hasta el presente(AU)

The authors present a case of granular cell tumor (myoblastoma) of the anal region in a woman aged 54, who was attended at "Joaquin Albarrán" Clinical Surgical Hospital due to a palpable "cyst" in the anal edges. The treatment applied consisted in local resection of the tumor. Histopathologic and immunohistochemical patterns were analyzed and they corresponded to those reported in medical literature(AU)

Dermatofibroma con células granulares: a propósito de un caso y revisión de la literatura / Granular cell dermatofibroma: a case report and review of the literature

PResentamos un caso de dermatofibroma epitelioide rico en células granulares. Solamente se han descrito 11 casos de dermatofibroma de células granulares, de los cuales sólo tres tienen rasgos epitelioides. Es importante reconocer este subtipo de dermatofibroma, ya que puede confundirse con un gran número de procesos benignos o malignos, de diferente aplicación pronóstica y terapeútica (AU)

Granular cell tumor of the penis in a 5-year-old boy.

We evaluate a rare case of a 5-year-old boy with granular cell tumor of the penis, located on the coronal margin. We discuss the anatomic distribution of granular cell tumors, noting the marked female predominance of genital involvement and reviewing the distribution of granular cell tumors by site in a pediatric series. We also discuss clinical implications, management, and histogenesis.

Granular cell traumatic neuroma: a lesion occurring in mastectomy scars.

BACKGROUND: Granular cell changes can be observed in a variety of benign and malignant tumors, and are seen more commonly in granular cell tumors, which in about 5% of cases develop in the breast. Granular cells also have been observed in sites of previous trauma, such as surgery, and are found to be inflammatory reactions of histiocytic origin. METHODS AND RESULTS: We investigated, morphologically and immunohistochemically, 2 granular cell lesions occurring in mastectomy scars after surgery for carcinoma. Both lesions were composed of strands and nests of large granular cells, haphazardly set in a background of fibrous tissue, with sparse inflammatory infiltrates. Several tortuous hypertrophic nerve bundles were also embedded in the fibrous tissue. A few of these nerve bundles showed degenerative changes and contained granular cells. Immunohistochemically, granular cells were positive for S100 protein, neuron-specific enolase, vimentin, and CD68 antigen. CONCLUSIONS: We consider these proliferative lesions of peripheral nerves to have the features of both granular cell tumor and traumatic neuroma. These cases indicate that traumatic neuroma can undergo extensive granular cell changes and constitute a previously unrecognized entity, which we provisionally label granular cell traumatic neuroma. Granular cell traumatic neuroma has to be taken into consideration when evaluating lesions occurring at mastectomy scars and should be differentiated from malignant tumors with granular cells, such as apocrine carcinoma and alveolar soft part sarcoma.

Benign neural tumors of the oral cavity: a comparative immunohistochemical study.

To determine if immunohistochemistry can be used as adjunct to the diagnosis and classification of oral benign neural tumors, we stained 77 neurally differentiated tumors with a panel of neural-associated antibodies (S-100 protein, CD57, epithelial membrane antigen, factor XIIIa, CD34, CD68, collagen IV). Using standard histologic criteria, we identified 13 schwannomas, 16 neurofibromas, 23 traumatic neuromas, 16 palisaded and encapsulated neuromas, and 9 granular cell tumors from archived oral pathology specimens. Silver stains showed that neurofibromas, traumatic neuromas, and palisaded and encapsulated neuromas consistently contained axon filaments. Although all neural tumors contained S-100-positive cells, schwannomas and palisaded and encapsulated neuromas contained the most. All tumors expressed CD57; traumatic neuromas were stained intensely and the others stained weakly. The consistent epithelial membrane antigen capsular staining of schwannomas and the absence of factor XIIIa-positive dendritic/spindle cells helped distinguish these tumors from others. Many CD34-positive cells were found in schwannomas, and few were found in palisaded and encapsulated neuromas. Variable numbers CD68-positive cells were seen in all neural tumor types; some of these cells appeared to be macrophages and mast cells, but many were thought to be Schwann cells expressing this antigen. Collagen IV staining, apparently representing basement membrane, was generally a feature of all benign neural tumors. The immunophenotype of the granular cells of the GCTs was S-100+, CD57+, and collagen IV+ supporting the putative neural origin of these tumors. We conclude that neural origin/differentiation of a connective tissue tumor can be confirmed with stains for S-100 protein, epithelial membrane antigen, CD57, and collagen IV. Staining patterns and intensities associated with the panel of antibodies tested can be useful in tumor classification.

Granular cell myoblastoma. Review of the literature and report of a case.

The origin and nature of granular cell myoblastoma (GCM) have been debated since the original description of a granular cell tumor by Abrikossoff in 1926. Many cell types have been implicated in its histogenesis, including muscle cells, histiocytes, fibroblasts, neural sheath cells and undifferentiated mesenchymal cells, but the origin of the lesion remains still controversial. The authors present a review of the clinical features and the histopathologic and histochemical findings of this nebulous entity. They also report a case of granular cell myoblastoma of the tongue.

Granular cell tumour and leiomyomatosis of the esophagus--a non-coincidental association?

One case of esophageal granular cell tumour (GCT) associated with diffuse leiomyomatosis of the distal esophagus is presented. The rarity of each of the lesions per se raises the possibility that the association between GCT and diffuse leiomyomatosis, a previously unreported finding, is not coincidental. In view of the present knowledge on both conditions we suggest that an underlying genetic alteration may be responsible for the hereby described association.

Granular cell tumor of vulva on episiotomy scar.

The granular cell tumor (GCT) is a rare neoplasm derived from Schwann cells and is considered to be a benign tumor. The vulvar region is one of the common sites for these lesions. Vulvar occurrence of GCT constitutes about 7% of cases. To our knowledge, this is the first case of granular cell tumor of the vulva on an episiotomy scar. GCT should be considered in the differential diagnosis of a benign tumor of the vulva and reactive granular cell lesions.

Tumor de células granulares da vulva / Granular cell tumor of the vulva

O tumor de células granulares pode ocorrer em diversos órgåos, sobretudo língua e pele. A vulva raramente é atingida, apenas em 5,3 por cento das oportunidades. Descrevemos um tumor nesta localizaçåo, mais propriamente no lábio direito e 1/3 superior da vulva, numa paciente com 37 anos de idade. A doente referia tumor no mesmo local há dois anos atrás, e acompanhava-a um relatório microscópico de sarcoma de vulva. Foi realizada uma vulvectomia simples com linfadenectomia parcial ipsilateral. O anatomopatológico demonstrou tumor de células granulares. Os linfonodos estavam livres e a paciente apresentava-se bem, após oito anos de evoluçåo. Tal tumor geralmente tem evoluçåo benigna e admite cirurgia conservadora. O fato de ser recidivado e o exame anterior ter demonstrado um sarcoma, erroneamente diagnosticado, induziram-nos a indicar cirurgia mais radical

Spontaneous brain and spinal cord/nerve neoplasms in aged Sprague-Dawley rats.

Primary malignant neoplasms of the brain and spinal cord occurred in 20/718 male (2.8%) and in 13/717 female (1.8%) Crl:CD Br strain Sprague-Dawley rats. Of 33 neoplasms, 30 were found in brain while 3 were in the spinal cord. In males and females, the most common brain neoplasm was astrocytoma (13 males, 9 females). Other neoplasms, granular cell tumor (1 male), mixed glioma (2 males, 1 female), reticulosis (1 male, 2 females), and oligodendroglioma (2 males), were especially uncommon. Spinal cord neoplasms included 2 schwannomas (1 male, 1 female) and an astrocytoma (1 male). The overall brain neoplasm incidence was similar for males (2.8%) compared to data compiled for this strain, and there was a 2-fold increase for females (1.8% vs 0.9%) compared to available incidence data.

[Granular cell tumor of the vermiform appendix. Case presentation with discussion of histogenesis]. / Granularzelltumor der Appendix vermiformis. Falldarstellung mit Diskussion der Histogenese.

Granular cell tumor is a rare lesion to the appendix. A case of that kind was recorded by the authors from a man, 32 years of age, who underwent surgery for appendicitis. Presence of a granular cell tumor was histologically, histochemically, and immunohistologically verified. Histogenesis of granular cell tumors is not well known, which prompted the authors to summarise some of their recent findings for discussion.