Clear cell dermatofibroma

This series presents six cases of a rare variant of dermatofibroma, characterized by marked clear cell change. All lesions occurred on the lower extremities of middle-aged adults (four women, two men), mostly with the clinical diagnosis of fibrohistiocytic lesion. Histological examination revealed well circumscribed, faintly stained dermal to subcutaneous lesions which were due to the overwhelming presence of clear cells (<90%), some with prominent PAS-positive cytoplasmic granulation. Overlying epidermal hyperplasia as well as storiform arrangement of spindle cells, sclerotic collagen and some interspersed lympho-histiocytic infiltrate at the periphery of the lesion indicated the fibrohistiocytic origin. Individual histopathological peculiarities included : bizarre giant cells in two cases, prominent perivascular lympho-histiocytic response, perifollicular arrangement and haemangiopericytoma-like features with iron deposition in one case each. Immunohistochemically three of four lesions showed moderate reactivity for factor XIIIa and two of four with an anti-metallothionen marker E9, but were otherwise negative with a broad panel of markers. Electronmicroscopy in two cases revealed large pools of glycogen beside focal, prominent endoplasmic reticulum and lysosomes in some granular cells, but only optically translucent cells in cases of clear cells. Recognition of clear cell dermatofibroma is important as the differential diagnosis includes some entities with more serious outcome/considerations such as metastases of renal cell carcinoma, xanthogranulomatous reactions, balloon cell naevus/melanoma and clear cell sarcoma.     

Clear cell dermatofibroma

This series presents six cases of a rare variant of dermatofibroma, characterized by marked clear cell change. All lesions occurred on the lower extremities of middle-aged adults (four women, two men), mostly with the clinical diagnosis of fibrohistiocytic lesion. Histological examination revealed well circumscribed, faintly stained dermal to subcutaneous lesions which were due to the overwhelming presence of clear cells (<90%), some with prominent PAS-positive cytoplasmic granulation. Overlying epidermal hyperplasia as well as storiform arrangement of spindle cells, sclerotic collagen and some interspersed lympho-histiocytic infiltrate at the periphery of the lesion indicated the fibrohistiocytic origin. Individual histopathological peculiarities included : bizarre giant cells in two cases, prominent perivascular lympho-histiocytic response, perifollicular arrangement and haemangiopericytoma-like features with iron deposition in one case each. Immunohistochemically three of four lesions showed moderate reactivity for factor XIIIa and two of four with an anti-metallothionen marker E9, but were otherwise negative with a broad panel of markers. Electronmicroscopy in two cases revealed large pools of glycogen beside focal, prominent endoplasmic reticulum and lysosomes in some granular cells, but only optically translucent cells in cases of clear cells. Recognition of clear cell dermatofibroma is important as the differential diagnosis includes some entities with more serious outcome/considerations such as metastases of renal cell carcinoma, xanthogranulomatous reactions, balloon cell naevus/melanoma and clear cell sarcoma.     

Myxoid dermatofibroma

AIMS: This report presents seven cases of a rare variant of dermatofibroma, characterized by marked mucinous stromal changes. METHODS AND RESULTS: In this retrospective clinicopathological study, lesions preferentially occurred on the lower extremities of young to middle-aged females. Clinical (differential) diagnoses included: dermatofibroma (two cases), cyst, tophus, ganglion and neurofibroma. Histology revealed well circumscribed, faintly stained dermal to subcutaneous lesions which contained abundant stromal mucin. A variable amount of spindle-shaped cells, occasional lymphocytes and fine collagen fibres were also seen. Epidermal hyperplasia above as well as storiform arrangement of spindle cells and some sclerotic collagen at the periphery of the lesion indicated the fibrohistiocytic origin. Individual histopathological features included: bizarre giant cells, perifollicular arrangement and seas of mucin with pseudovascular clefts in one case each. Immunohistochemically, all lesions were positive for KiM1p (> 50% of the cells). Moreover, two lesions showed moderate reactivity for factor XIIIa (10-25%), one each with NK1C3 (> 90%) and smooth muscle actin (50%), but were otherwise negative with a broad panel of markers. Electron microscopy in one case revealed large pools of mucin interspersed by a moderate number of fibrocytes with fine fibrillary collagen. CONCLUSION: This series confirms myxoid dermatofibroma as a rare variant of fibrohistiocytic tissue response; our series also indicates that many of these lesions might be misinterpreted as cutaneous myxoma.     

Granular cell change in smooth muscle tumours of skin and soft tissue

Nine smooth muscle tumours, arising at a variety of sites and showing granular cell change of their cytoplasm, have been studied morphologically and immunohistochemically. The age of the patients ranged from 6 to 78 years (median 42 years); seven patients were female. Two tumours each arose in the dermis or subcutaneous tissue while the other five cases were situated in deeper soft tissue. Three of the lesions arose in the lower limbs, two in the pelvis and one each in the regions of the elbow, shoulder, breast and buttock. Follow-up in eight patients was available and revealed local recurrence in three and pulmonary metastases in two cases. All cases showed at least focally the light microscopic features of a smooth muscle tumour and demonstrated moderate to strong positivity for α-smooth muscle actin. Five were also HHF-35 positive and three were desmin positive. Noteworthy was strong positivity for the 'melanoma associated' antigen NKI/C3 in all cases. Six cases stained also weakly positive for NSE, but all were S-100 protein negative. The former is not specific but is the most reliable marker of lesions showing granular cell change. Granular cytoplasmic change represents simply a cytological phenotype, apparently representing a characteristic metabolic alteration, not exclusively associated with Schwann cell tumours. Tumours containing granular cells are best classified according to their line of specific cellular differentiation if possible.     

Islet cell tumour with vacuolated lipid-rich cytoplasm: a new histological variant of islet cell tumour

Aims : A previously unreported clear cell variant of islet cell tumour of the pancreas is described. Methods and results : By light microscopy, the cytoplasm of the clear cells was finely reticulated and vacuolated. Immunohistochemical and electron microscopy studies confirmed the endocrine nature of the tumour. Conclusions : The clear cell morphology was due to the accumulation of lipid in the cytoplasm.     

Malignant granular cell tumour with intraperitoneal dissemination

An unusual case of a malignant granular cell tumour involving the peritoneal cavity and probably arising in the pelvis is reported. The light microscopic diagnosis was confirmed by electron microscopy and immunohisto-chemistry.     

Islet cell tumour with vacuolated lipid-rich cytoplasm: a new histological variant of islet cell tumour

Aims: A previously unreported clear cell variant of islet cell tumour of the pancreas is described. Methods and results: By light microscopy, the cytoplasm of the clear cells was finely reticulated and vacuolated. Immunohistochemical and electron microscopy studies confirmed the endocrine nature of the tumour. Conclusions: The clear cell morphology was due to the accumulation of lipid in the cytoplasm.     

Granular cell tumours of the lower respiratory tract

Granular cell tumours rarely involve the lower respiratory tract. We report eight cases surgically resected at our institution. There were four females and four males, aged between 18 to 56 years (mean 40). One tumour associated with a peripheral lung adenocarcinoma was asymptomatic. The other lesions presented with obstructive pneumonitis (3 cases), haemoptysis (2), dyspnea (1) or cough (1). These tumours were tracheal (1) or bronchial (6) and one case was located in the lung parenchyma. Four cases were multicentric with associated lesions located in a bronchus (2), the oesophagus (1) or a mediastinal lymph node (1). All tumours, with the largest diameter ranging from 0.5–4.5 cm, were histologically invasive. The tumours were positive for S-100 protein, neuron specific enolase, KP1 (CD68) and vimentin. No tumour expressed desmin, keratin or p53 oncoprotein. Our study demonstrates that, in spite of marked anatomical and clinical polymorphism, the rare granular cell tumours of the lower respiratory tract have a constant histological appearance. Our observations confirm that large tumours (> 8–10 mm) usually extend beyond the tracheo-bronchial cartilages and, therefore, only surgical treatment may avoid recurrence.     

颗粒细胞瘤15例临床病理分析

目的探讨颗粒细胞瘤的组织起源及临床病理学特征。方法回顾分析15例颗粒细胞瘤的临床资料及组织学形态特征,并采用免疫组化(SP法)观察其免疫表型。结果良性颗粒细胞瘤13例,恶性颗粒细胞瘤2例。男性5例,女性10例,年龄19~69岁,平均年龄41·6岁,2例恶性颗粒细胞瘤年龄分别为67岁和69岁。良性颗粒细胞瘤直径0·4~5·3cm,平均2·3cm,2例恶性颗粒细胞瘤直径分别为6和14cm。均为单发病例,临床上主要表现为真皮、皮下或黏膜下孤立性无痛性结节,分别位于腰部3例、腋下、胸壁各2例,乳腺、上臂、子宫、肛周、声带、食管、结肠、舌部各1例。病理组织学上,良性颗粒细胞瘤的肿瘤细胞通常有比较丰富的嗜酸性颗粒状胞质和小而深染的胞核,而恶性颗粒细胞瘤的肿瘤细胞中可见带有明显核仁的空泡状核,细胞核明显异型及部分细胞呈梭形。免疫组化示神经标记物NSE、S-100蛋白强阳性,表达溶菌酶的标记物CD68也强阳性,而表达平滑肌和横纹肌的标记物SMA、MG均阴性。结论颗粒细胞瘤为来源于雪旺细胞的肿瘤,恶性者少见,大多发生在年龄大的患者,且肿瘤体积比较大。     

Granular cell tumour of the colon with extensive sclerosis

Granular cell tumour (GCT) is a rare, usually benign, mesenchymal lesion that can occur in nearly any organ, but has a proclivity for the oral cavity, skin and subcutaneous tissue. They occasionally arise in the gastrointestinal tract (GIT) where the oesophagus is most commonly involved. Occurrence in the colorectum is unusual. We report a case of a 73 year-old man with an incidentally discovered GCT with extensive sclerosis in the caecum. Microscopically, a well-circumscribed, paucicellular nodule was identified in the submucosa with prominent hyalinisation and focal myxoid change. Scattered, finely granular cells expressing S100, inhibin and calretinin were identified. CD117 and DOG-1 were negative. This case was made challenging by the prominent sclerosis with only focally visible granular cells, however, the overall features were those of a GCT of the colon. We highlight the morphological and immunohistochemical features of this rare entity in the colon, and discuss the differential diagnosis. In this era where incidental polyps and submucosal lesions are increasingly being detected by endoscopy, knowledge and recognition of GCT in the colon is important as they are generally benign with a good prognosis following complete excision.     

Granular cell tumour of the mammary gland simulating malignancy

Summary Primary granular cell tumours of the breast in 35 2and 55 year old women were studied by light microscopy, transmission electron microscopy and immunohistochemistry. Light and electron microscopy revealed a neural origin of the tumours and this was further substantiated by immunohistochemical studies, with positive S-100 protein reaction and negative reactions for surface heavy and light chains, CEA, alfa-1-antitrypsin, muramidase and GFA-protein. Granular cell tumour of the mammary gland is a very rare tumour. Clinically it sometimes simulates carcinoma because of its fibrous consistency, fixation to pectoral fascia and skin retraction. The diagnosis of granular cell tumour should be included in the differential diagnosis of carcinoma of the breast.The granular cell tumour is derived from neuro-ectodermal tissue. Whether it represents a neurogenic cell-confined metabolic disturbance with lysosomal activation, or a true neoplasm remains to be elucidated.     

Dermal non-neural granular cell tumour (so-called primitive polypoid granular cell tumour): a distinctive entity further delineated in a clinicopathological study of 11 cases

AIMS: Cutaneous and soft tissue granular cell tumour is a well-characterized benign neoplasm of neural origin. However, there remains a subcategory of granular cell tumour, first described by Le Boit as 'primitive polypoid granular cell tumour', that shows no obvious line of differentiation. The aim of this study is to further the characterization of this lesion by undertaking a clinicopathological review. METHODS AND RESULTS: Eleven cases of dermal non-neural granular cell tumour were retrieved from one of the authors referral archives (E.C.) and both the histology and immunohistochemistry reviewed. Clinical data with follow-up were obtained from the referring pathologists. The lesions most commonly occurred in young to middle-aged adults (nine cases, median = 33 years, age range 6-56 years), with a slight female predominance. They presented as painless nodules, mainly on the extremities or face. Local excision was the treatment of choice and up to date follow-up reveals no sign of recurrence. Histologically, eight cases were polypoid, while three cases were endophytic. The tumours were composed of elongated spindle-shaped to polygonal or round cells with prominent granular cell change, and tumour nuclei showing mild focal atypia to rare moderate atypia. Mitotic activity ranged from one to nine mitoses per 10 high-power fields (median = 2, mean = 3.8). Immunohistochemical labelling of the tumour cells demonstrated expression for NKI-C3 (n = 11), focal, weak positivity for CD68 (n = 10) and FXIIIa (n = 2). There was negative staining for S100 protein, smooth muscle actin, Melan-A, CD34, desmin and cytokeratin. CONCLUSIONS: This analysis of 11 cases contributes to the characterization of this recently described entity, which despite some atypical histological features and no obvious line of differentiation, behaves in a completely indolent fashion.     

Granular cell angiosarcoma of the skin: histology, electron microscopy and immunohistochemistry of a newly recognized tumor

We report a unique angiosarcoma of the skin of the face in which a large part of the tumour was of granular cell appearance. Histologically the granular cells resembled those of conventional granular cell tumours. By electron microscopy the granules were identical to those of granular cell tumours but other features were lacking. Stains for vimentin and factor VIII related antigen were positive, but for S-100 protein and CEA were negative. The occurrence of granular cell change in an angiosarcoma supports the view that granular cell tumours are histogenetically diverse.     

Granular cell tumor of the breast

We report a case of a 43-yr-old woman with a granular cell tumor of the breast. She presented with a palpable mass of the left breast of 2-yr duration. On physical examination, a firm, painless, well-defined mass located at the union of the upper quadrants was observed and a palpable homolateral axillary lymph node. The tumor was dense with ill-defined borders at mammography and hypoechoic, hypovascular, and poorly limited at ultrasonography. Fine needle aspiration cytology of the lesion was performed. Cytologic examination revealed the presence of highly cellular material, composed of both large cohesive groups and single cells often admixed with connective tissue. These cells had ill-defined abundant granular cytoplasm and bland regular small nuclei. Nucleoli were inconspicuous. Neither mitoses nor necrosis were noted. The cytological diagnosis of granular cell tumor of the breast was confirmed by histological examination of the surgical specimen following a breast lumpectomy.     

Granular cell astrocytoma

Granular cell astrocytoma (GCA) is a rare morphologic variant of astrocytomas, characterized by a prominent component of plump granular tumor cells. It has an aggressive clinical course as compared with conventional astrocytoma of the same grade. As its cytologic feature resembles that of a foamy histiocyte and, histologically, the tumor is rich in arborizing capillaries, it can be difficult to distinguish GCA from non-neoplastic diseases such as infarct or demyelinating disease. In this paper, a case of a GCA in a 28-year-old full-term pregnant woman suffering from a sudden episode of seizure during delivery is described, focusing on histopathological, immunohistochemical, and ultrastructural features. Histopathology and immunohistochemical phenotype of this tumor were identical to the previous reports. Ultrastructurally, secondary lysosome (so-called lipofuscin bodies) granules were present but not numerous; instead, many mitochondria and unusual paracrystalline inclusions were found in each tumor cell. In our case, the light microscopic granular appearance might be produced not only by phagolysomes but also by numerous mitochondria and paracrystalline inclusions.     

Malignant osteoclastoma-like giant cell tumour of the renal pelvis

We report the fourth case of an osteoclastoma-like giant cell tumour of the renal pelvis. A special feature was that although thorough sampling of the tumour showed an osteoclastoma-like pattern throughout, it was intimately associated with carcinoma in situ change of the adjacent transitional epithelium and this provides further support for the view that these tumours are of epithelial derivation. However, immunohistological and ultrastructural studies failed to reveal epithelial features within the tumour cells and the possible significance of this finding is discussed.