Mechanism of traumatic neuroma development

We suggest that symptomatic traumatic neuromas - benign lesions of incompletely understood etiology - develop when neural fiber regeneration occurs in the presence of excessive fibrous tissue proliferation. Subsequent contraction of wound and scar myofibroblasts leads to compression of the regenerating nerve fibers and further stimulation of the overgrowth of their perineurial cells as a protective response. This chronic process leads to a slow enlargement of the proliferating mass and the typical histological picture of a traumatic neuroma, in which multiple interlacing fascicles of nerve fibers are encased in condensed fibrous tissue. To avoid the development of a traumatic neuroma, we propose that an injured or a transected nerve should be placed out of the site of potential excessive fibroproduction and/or that all external factors leading to excessive fibroproduction development be eliminated from the wound site.     

The unique simultaneous occurrence of granular cell tumor, gastrointestinal stromal tumor, and gastric adenocarcinoma

Granular cell tumors are generally benign oncocytoid lesions of schwannian origin that are often incidental findings in many locations. Gastrointestinal stromal tumors occur in older adults and express the c-Kit protein (CD117). Both of these tumors have been described in association with many other entities; however, they have never been reported to occur jointly. This report is prompted by the simultaneous appearance of 2 granular cell tumors, a gastrointestinal stromal tumor, and a gastric adenocarcinoma in a 65-year-old woman with a history of breast carcinoma and granular cell tumor. To our knowledge, this is the first case report of these tumors occurring simultaneously.     

Intrarenal solitary fibrous tumor of the kidney report of a case with emphasis on the differential diagnosis in the wide spectrum of monomorphous spindle cell tumors of the kidney

Solitary fibrous tumor (SFT) is a neoplasm that can occur in the urogenital tract, and is also reported occurring in the spermatic cord, seminal vesicles, urinary bladder, prostate, and kidney. Furthermore, it is most important to consider its existence in the kidney, because it is usually diagnosed as renal cell carcinoma pre-operatively. To our knowledge, only 10 cases of SFT have been reported in the kidney to date. We report the clinico-pathological features of an intrarenal SFT occurring in a 31-year-old woman. The tumor, measuring 8.6 cm in its greatest diameter, completely replaced the cortex and the medulla of the middle region of the right kidney, compressing the pelvis. Radiological imaging was consistent with a renal cell carcinoma. Histologically, the tumor was composed of a proliferation of bland-looking vimentin+, CD34+, bcl2+ and CD99+ spindle cells exhibiting a haphazard to storiform growth pattern, pushing borders, and a low mitotic rate (2 mitoses x 10 HPF). We placed emphasis on the differential diagnostic problems, i.e., its differentiation from other primary monomorphous benign and malignant spindle cell tumors of the kidney, such as fibroma, benign fibrous histiocytoma, hemangiopericytoma, inflammatory myofibroblastic (pseudo-)tumor, leiomyoma, angiomyolipoma with predominant spindle cell smooth muscle component, benign peripheral nerve sheath tumors, renal mixed epithelial/stromal tumors, adult type mesoblastic nephroma, fibrous type monophasic synovial sarcoma, malignant peripheral nerve sheath tumors, fibrosarcoma, and low-grade fibromyxoid sarcoma.     

Oncocytic and granular cell neoplasms of the central nervous system and pituitary gland.

Oncocytic transformation is an infrequent event within the central nervous system and is limited to neoplasms of the choroid plexus, meninges, and pituitary gland. Oncocytic modifications in choroid plexus tumors seem to occur predominantly in adult patients and in the fourth ventricle and do not seem to reflect any particular biological behavior. Meningiomas showing oncocytic differentiation have been recently described and this variant probably behaves more aggressively. Pituitary oncocytomas are regarded as a subtype of null cell adenomas. Oncocytic tumors have a significantly higher risk of progression with a higher recurrence rate after radiotherapy. Oncocytic changes in astrocytic neoplasms are rare. More frequently, astrocytomas can show granular changes that result in neoplasms composed of cells with granular cytoplasm and eccentric nuclei resembling foamy macrophages. Granular cell astrocytomas may mimic non-neoplastic lesions such as cerebral infarction and demyelinating disease. Cells with granular bodies are frequent in pilocytic astrocytoma, pleomorphic xanthoastrocytoma, and ganglion cell tumors. Their presence is considered a useful diagnostic finding to distinguish these low-grade lesions from malignant gliomas. A rare neoplasm is the granular cell tumor of the infundibulum that, when symptomatic, has to be differentiated from pituitary adenomas and other more common lesions of the sellar region.     

Laryngeal granular cell tumor; rare location

Granular cell tumors are benign subcutaneous or submucosal lesions of neurogenic origin. In this case study one patient was diagnosed and treated successfully with complete surgical resection of a laryngeal granular cell tumor that was originated from the left arytenoid region that very rare location. There is no evidence of recurrence 2 years after surgery. Granular cell tumors should be considered in the differential diagnosis of laryngeal masses, particularly in the posterior glottis.     

Low-affinity nerve growth factor receptor (p75) in dermatofibrosarcoma protuberans and other nonneural tumors: a study of 1,150 tumors and fetal and adult normal tissues

Low-affinity nerve growth factor receptor (p75) is a member of the tumor necrosis factor receptor family. It may modulate the binding of nerve growth factor (NGF) to the functional high-affinity receptor tyrosine kinase (trk) A. NGF is thought to be responsible for growth, apoptosis, and function of the nervous system. The presence of this receptor (p75) was determined in a large group of neural and nonneural tumors and fetal and adult tissues. One thousand one hundred fifty tumors were analyzed with monoclonal antibody for p75, along with selected normal fetal and adult tissues. Immunoreactivity for p75 was present in adult pericytes, perivascular fibroblasts, basal cells of several types of epithelia, perineurial cells, and dendritic reticulum cells. Additionally, a wide zone of subepithelial mesenchyme and skeletal muscle were positive in the first-trimester fetus, but were diminished or negative in the adult. Consistently positive nonneural mesenchymal tumors included dermatofibrosarcoma protuberans (DFSP), embryonal and alveolar rhabdomyosarcoma, synovial sarcoma, and spindle cell hemangio(endotheli)oma. Schwann cell tumors, ganglioneuroma, granular cell tumor, and malignant peripheral nerve sheath tumor (MPNST) were also p75 positive. Mesenchymal nonneural tumors that were variably positive (32% to 69%) for p75 included fibrosarcoma variants, solitary fibrous tumor, hemangiopericytoma, spindle cell lipoma, Ewing's sarcoma, mesenchymal chondrosarcoma, and malignant melanoma. Nervous system tumors such as paragangliomas, neuroblastoma, meningioma, and perineurioma and nonneural mesenchymal tumors, including extraskeletal osteosarcoma, benign fibrous histiocytomas, fibromas, alveolar soft part sarcoma, epithelioid sarcoma, smooth muscle and gastrointestinal stromal tumors, and angiosarcomas, were almost always negative for p75. Epithelial tumors that were consistently positive included mixed tumor and adenoid cystic carcinoma, whereas mesothelioma, adenocarcinomas, and most squamous cell carcinomas were negative. p75 is not a specific marker for nerve sheath tumors. It is present in a variety of other mesenchymal tumors including synovial sarcoma and in CD34-positive tumors such as DFSP, spindle cell lipoma, and hemangiopericytoma. The presence of p75 in nonneural tumors such as DFSP and rhabdomyosarcoma mimic its presence in early fetal mesenchyme and skeletal muscle, suggesting oncofetal expression in these tumors. p75 may be useful to distinguish DFSP from benign fibrous histiocytoma.     

创伤性神经瘤模型的构建及评价

文题释义： 神经瘤：1811年Odier首先提出神经瘤的概念,周围神经受到创伤后,神经纤维断裂,神经轴突在变性的基础上开始再生,在神经纤维的再生过程中,两断端组织增生过多,断端再生的轴突因瘢痕障碍,不能成功长入远端神经中,近端轴突和胞体在内源性神经生长因子及其靶器官分泌的神经生长因子的刺激和诱导下,持续在障碍物上向各个方向出芽生长、卷曲、甚至反折、相互缠绕,加之期间的纤维结缔组织生长、增生,并逐渐增长形成以纤维结缔组织为主的假性神经瘤。 神经纤维瘤病：为常染色体显性遗传病,是基因缺陷使神经嵴细胞发育异常导致多系统损害。创伤性神经瘤需与肥大性瘢痕及神经纤维瘤鉴别,后两者也可在外伤后发生,但组织学显示增生组织主要为胶原和成纤维细胞,无神经组织改变。 背景：创伤性神经瘤是周围神经损伤的常见并发症,国内外通过创伤性神经瘤模型进行周围神经修复、再生的基础研究较少见。 目的：建立创伤性神经瘤模型并进行鉴定。 方法：实验方案经中国人民解放军总医院动物实验伦理委员会批准。选择15只8周健康SD大鼠,显微镜下暴露坐骨神经,用显微剪剪断股后皮神经以远1 cm处的坐骨神经,11-0显微线将神经近端缝合于周围肌肉上,远端神经反折后旷置,3周后使用超声和组织学验证神经瘤是否形成。 结果与结论：①造模3周后,超声可见近端神经明显梭形膨大,为一低回声实质结节,不伴回声;②大体观察可观察到近端神经膨大,质稍硬,纤维结缔组织增生,与周围组织粘连;③苏木精-伊红染色可见瘤体内纤维组织增生,神经纤维杂乱生长,免疫荧光染色(S100、NF200)可见瘤体内许旺细胞和神经轴突不规则增生;④结果表明：实验成功构建了创伤性神经瘤模型。 ORCID: 0000-0002-3134-5488(汪靖);0000-0002-4517-734X(鲁长风) 中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程     

Immunohistochemical demonstration of EMA/Glut1-positive perineurial cells and CD34-positive fibroblastic cells in peripheral nerve sheath tumors.

To clarify the cellular composition of various peripheral nerve tumorous lesions (traumatic neuroma, 5 cases; schwannoma, 10 cases; neurofibroma, 14 cases; perineurioma, 3 cases; conventional malignant peripheral nerve sheath tumor (MPNST), 7 cases; perineurial MPNST, 4 cases), expression of several markers specific to nerve sheath cells, including glucose transporter protein 1 (Glut1) and CD34, were immunohistochemically investigated with highly sensitive detection methods. In normal nerves and neuromas, perineuriums were positive for Glut1 as well as for epithelial membrane antigen (EMA), and there were some CD34-positive fibroblast-like cells in the endoneurium. Schwannomas consisted principally of S-100 protein-positive Schwann cells, whereas a few CD34-positive fibroblastic cells were present in Antoni B areas. Neurofibromas and conventional MPNST exhibited a mixed proliferation of S-100 protein-, EMA/Glut1-, and CD34-positive cells, indicating a heterogeneous composition of the constituents. The catalyzed signal amplification (CSA) system demonstrated more numerous EMA-positive perineurial cells in neurofibromas than did the ENVISION+ method. Perineurial cell tumors (benign and malignant) were composed of EMA/Glut1-positive and S-100 protein-negative tumor cells. The present study confirmed the characteristic cellular composition to each nerve sheath tumor immunohistochemically and showed the usefulness of the nerve sheath cell markers. Glut1 as well as EMA are specific to perineurial cells, and CD34 seems to be immunoreactive to endoneurial fibroblasts.     

Granular cell variant of neurofibromatosis: ultrastructure of benign and malignant tumors

A case of neurofibromatosis with a metastasizing malignant tumor is presented. The benign lesions were identified by light microscopy as neurofibromas containing granular cells typical of granular cell tumors. The malignant tumor was classified as a malignant granular cell tumor. Ultrastructural studies demonstrated common histogenetic and subcellular features of the benign and malignant tissues. The case is the first reported in which granular cells are seen in the lesions. The typical granular cell morphologic features of the malignant lesion support the concept of Schwann cell derivation of this group of tumors.     

Intra-abdominal spindle cell lesions: a review and practical aids to diagnosis

Intra-abdominal spindle cell lesions are uncommon and often present a diagnostic challenge. An important group of such lesions are the gastrointestinal stromal tumours. Other intra-abdominal spindle cell lesions include fibromatosis, various sarcomas-in particular, leiomyosarcoma, liposarcoma, and malignant peripheral nerve sheath tumour-and, in women, endometrial stromal sarcoma. Less common lesions are inflammatory myofibroblastic tumours, the mesenteric spindle cell reactive lesions, retroperitoneal fibrosis, and solitary fibrous tumour. A variety of intra-abdominal tumours of nonmesenchymal origin may have a spindle cell/sarcomatoid morphology; these include sarcomatoid carcinoma, malignant melanoma and, in women, sarcomatoid granulosa cell tumour. Finally, metastatic sarcomas from pelvic or extra-abdominal organs need also be considered. A set of practical aids to the diagnosis of intra-abdominal spindle cell lesions is presented to assist pathologists dealing with such lesions, particularly with regards to the consideration of differential diagnoses.     

A survey of clusterin and fascin expression in sarcomas and spindle cell neoplasms: strong clusterin immunostaining is highly specific for follicular dendritic cell tumor.

Clusterin, a glycoprotein implicated in many cellular functions including apoptosis, has recently been shown to be strongly expressed in follicular dendritic cell tumors, and to be absent or only weakly expressed in other dendritic cell tumors. Fascin has also been investigated as a potential marker of dendritic cell neoplasms. We evaluated staining for antibodies directed against these two antigens in 202 spindle cell tumors, including cases of follicular dendritic cell tumor (n=14), interdigitating dendritic cell tumor (n=7), leiomyosarcoma (n=17), inflammatory myofibroblastic tumor (n=13), inflammatory pseudotumor (n=2), spindle cell thymoma (n=17), synovial sarcoma (n=11), fibrosarcoma (n=14), liposarcoma (n=27), gastrointestinal stromal tumor (n=13), malignant fibrous histiocytoma (n=18), angiomatoid fibrous histiocytoma (n=4), angiosarcoma (n=10), malignant peripheral nerve sheath tumor (n=8), malignant melanoma (n=16), and spindle cell carcinoma (n=11). Among these spindle cell neoplasms, strong diffuse clusterin staining had an overall specificity of 93% and a sensitivity of 100% for follicular dendritic cell tumor. Clusterin staining was least reliable in distinguishing follicular dendritic cell tumor from spindle cell thymoma or malignant fibrous histiocytoma, but these are entities that usually can be distinguished by clinical and morphologic data. Rare cases of leiomyosarcoma, fibrosarcoma and angiosarcoma may show strong clusterin staining. Fascin staining was very nonspecific among spindle cell tumors and thus does not imply a dendritic cell lineage.     

Infiltrating granular cell tumor of the esophagus: a description of two cases

Granular cell tumor of the esophagus is an unusual tumor. It presents usually as a small and well limited lesion, localized in the mucosa or the submucosa. We report two cases of granular cell tumor of the esophagus, remarkable for their infiltrative growth. The tumor invaded the esophageal muscularis propria in one case and went through the adventitia in the other. There was no recurrence 1 year and 7 years after surgery, despite an incomplete resection in the second case. Thirteen cases of infiltrative granular cell tumors of the esophagus have been published. They are usually responsible for dysphagia. They can invade the muscularis propria and the adventitia as well as the periesophageal organs. There is no recurrence, even after an incomplete resection. The infiltrative feature of the granular cell tumors of the esophagus, by itself, cannot be considered as a malignant feature. The diagnosis of malignant granular cell tumor of the esophagus lies on the discover of metastases.     

Atypical granular cell tumor of the thyroid: cytomorphologic features on fine needle aspiration

Granular cell tumors are uncommon soft tissue neoplasms of nerve sheath origin, which are predominately benign and are characterized by abundant granular cytoplasm, uniform nuclei, and indistinct cell borders. Features of malignancy include spindle cell morphology, necrosis, prominent nucleoli, increased nuclear to cytoplasmic ratio, nuclear pleomorphism, and increased mitotic rate. Granular cell tumors are most common in the soft tissues of the head and neck, but have only been rarely described in the thyroid gland. Here we report a case of an atypical granular cell tumor of the thyroid seen on fine needle aspiration, which displayed focal atypical cells with spindle cell morphology, increased nuclear to cytoplasmic ratio, and prominent nucleoli. The differential diagnosis of such findings is also presented.     

Multicentric encapsulated papillary oncocytic neoplasm of the thyroid: A case diagnosed by a combined cytological, histological, immunohistochemical, and molecular approach

Fine-needle aspiration (FNA) diagnosis of oncocytic lesions is challenging. In fact, oncocytic changes occur in inflammatory, hyperplastic, and neoplastic settings, including both benign and malignant tumors. The rare oncocytic variant of papillary thyroid carcinoma (PTC), shows papillae composed by cells with large oncocytic granular cytoplasm featuring clear PTC nuclear features. A morphological similar, but biologically distinct lesion, is the encapsulated papillary oncocytic neoplasia. Here, we first report on FNA, its cytological features together with histological, immunohistochemical, and molecular correlates.     

Granular cell basal cell carcinoma. Light microscopy,immunohistochemical and ultrastructural study

Summary Granular cell basal cell carcinoma (BCC) is a rare histological variant of BCC. In this, the fifth reported case, a 67-year-old male with BCC located on the nose, light microscopy examination showed a tumour with the classical configuration of nodular BCC, in which most cells had finely granular eosinophilic cytoplasm. Ultrastructural observation showed numerous lysosome-like granules filling the cytoplasm of tumour cells, along with numerous well-formed pentalaminate desmosomes. Immunohistochemical profile (including positivity for keratins C 5.2 and AE 1 and for Leu-M1), together with the presence of cytoplasmic tonofilament bundles and desmosomes, are consistent with the proposed epithelial origin of granular cells in this tumour.     

Congenital tumours of the salivary gland: a case report and review

A congenital epithelial tumour of the submandibular salivary gland, occurring in a child of 10 months, is described. The lesion appeared benign and consisted of basal type cells, showing ductal and acinar differentiation with myoepithelial cells. The associated fibrous stroma contained blood vessels and small nerve bundles. A few similar lesions have been reported in the past, some of which showed features of malignancy. Although various names have been proposed, we suggest that these lesions represent a single group derived from a primitive cell line and advocate the use of the term sialoblastoma.     

Xanthogranulomatous gastritis with pseudosarcomatous changes

Reported herein is a rare case of xanthogranulomatous inflammation of the gastric wall occurring in a 77-year-old man. Two submucosal lesions presented as rapidly enlarging nodules, and biopsy showed interweaving bundles of spindle cells with numerous atypical cells with marked nuclear pleomorphism. The differential diagnosis from mesenchymal malignancies, particularly from a malignant gastrointestinal stromal tumor, was difficult and immunohistochemical investigations could not improve the diagnostic accuracy of HE histology alone. Thus, an erroneous diagnosis of malignancy was made and a partial gastrectomy was performed. On macroscopic examination of the resected material, spontaneous regression of the lesions was observed and microscopic examination showed characteristic features of xanthogranulomatous inflammation; large numbers of foamy histiocytes including multinucleated giant cells were admixed with chronic inflammatory cells and fibrous reaction. Although the precise pathogenesis could not be elucidated, recognition of this unusual morphological appearance is of importance to avoid an overdiagnosis of malignancy.     

Follicular thyroid adenoma dominated by spindle cells: report of two unusual cases and literature review

Primary spindle cell neoplasms of the thyroid gland are quite rare. They encompass a heterogeneous group of benign and malignant lesions of mesenchymal and epithelial origin. We herein describe two unusual follicular thyroid adenomas dominated by spindle cells with occasional areas of colloid-forming follicular differentiation. The tumors affected a 77-year woman and a 70-year old man; both had a long-history of monoclonal gammopathy of unknown significance (MGUS). One tumor presented as a large cold thyroid nodule and the other was an autopsy finding. The tumors were predominantly composed of fibroblast-like spindled cells. One case showed prominent meningioma-like concentric perivascular arrangement and contained cytoplasmic melanin-like pigment. Stromal hyalinization was a prominent feature of both. By immunohistochemistry, the spindled cells expressed vimentin, pankeratin (KL1), thyroglobulin and TTF1 consistent with a follicular differentiation. They did not stain with calcitonin, CEA and other lineage-specific mesenchymal, neuroendocrine and melanocytic markers. There was no evidence of metastasis at autopsy (case 2) or at last follow-up 2 years after surgery (case 1). These cases demonstrate the diversity of follicular thyroid neoplasms and the unusual occurrence of extensive spindle cell metaplasia. These uncommon lesions need to be distinguished from spindle cell medullary carcinoma, paucicellular spindle cell anaplastic carcinoma, spindle cell foci in papillary and follicular carcinoma, solitary fibrous tumor and other rare benign and malignant mesenchymal lesions.     

STAT6 expression in spindle cell lesions of the breast: An immunohistochemical study of 48 cases

The diagnosis of spindle cell lesions of the breast parenchyma is challenging. Some of these lesions share the expression of CD34, posing differential diagnostic problems, especially in core biopsies. Recently, antibodies against the STAT6 C-terminal, are being used in paraffin-embedded tissues as a surrogate for identifying the NAB2–STA6 fusion gene which is considered a specific molecular marker for solitary fibrous tumor. Accordingly, we investigated the expression of STAT6 in a large series of uncommon spindle cell tumor-like and tumor lesions occurring primarily in the breast parenchyma. We collected 10 classic-type myofibroblastomas, 9 desmoid-type fibromatosis, 6 spindle cell metaplastic carcinoma, 5 benign fibroblastic spindle cell tumors, 3 solitary fibrous tumors, 7 pseudoangiomatous stromal hyperplasias, 2 reactive spindle cell nodules, 1 leiomyoma, 1 spindle cell lipoma, 1 case of inflammatory pseudotumor, 1 nodular fasciitis, 1 myxoma and 1 dermatofibrosarcoma protuberans. A diffuse and strong nuclear STAT6 expression was restricted only to solitary fibrous tumors, while the other lesions were negative or showed only weak cytoplasmic expression. The present study confirms that the demonstration of a diffuse and strong STAT6 nuclear staining is very helpful in distinguishing solitary fibrous tumor from other spindle cell mimics arising in the breast.     

Eosinophilic and granular cell tumors of the breast.

Eosinophilic and granular cell tumors of the breast are a heterogeneous group encompassing both epithelial and mesenchymal lesions. A granular appearance of the cytoplasm may be caused by the accumulation of secretory granules, mitochondria, or lysosomes. In the breast, mucoid carcinomas, carcinomas showing apocrine differentiation, and neuroendocrine carcinomas are well known entities, while tumors with oncocytic and acinic cell differentiation have been only recently recognized. An abundance of lysosomes is characteristic of Schwannian granular cell neoplasms, but smooth muscle cell tumors also may have this cytoplasmic feature. Awareness of all these possibilities when granular cells are found in breast lesions improves diagnostic accuracy and helps to avoid misdiagnosis of both benign lesions and malignant tumors.