Glycogen-rich pleomorphic xanthoastrocytoma with clear-cell features: confirmatory report of a rare variant with implications for differential diagnosis

Central nervous system space-occupying lesions with clear-cell features encompass a nosologically heterogeneous array, ranging from reactive histiocytic proliferations to neuroepithelial or meningothelial neoplasms of various grades and to metastases. In the face of such differential diagnostic breadth, recognizing cytoplasmic lucency as part of the morphological spectrum of some low grade gliomas will directly have an impact on patient care. We describe a prevailing clear-cell change in an epileptogenic left temporal pleomorphic xanthoastrocytoma surgically resected from a 36-year-old man. Mostly subarachnoid and focally calcified, the tumor was composed of fascicles of moderately atypical spindle cells with optically lucent cytoplasm that tended to intermingle with a desmoplastic mesh of reticulin fibers. Immunohistochemically, coexpression of S100 protein, vimentin, GFAP, and CD34 was noted. Conversely, neither punctate staining for EMA nor positivity for CD68 was seen. Mitotic activity was absent, and the MIB1 labeling index was 2-3% on average. Diastase-sensitive PAS-positive granula indicated clear-cell change to proceed from glycogen storage. Electron microscopy showed tumor cell cytoplasm to be largely obliterated by non-lysosomal-bound pools of glycogen, while hardly any fat vacuole was encountered. Neither ependymal-derived organelles nor annular lamellae suggesting oligodendroglial differentiation were detected. The latter differential diagnosis was further invalidated by lack of codeletion of chromosomal regions 1p36 and 19q13 on molecular genetic testing. By significantly interfering with pattern recognition as an implicit approach in histopathology, clear-cell change in pleomorphic xanthoastrocytoma is likely to suspend its status as a “classic”, and to prompt more deductive differential diagnostic strategies to exclude look-alikes, especially clear-cell ependymoma and oligodendroglioma.     

Cerebellar pleomorphic xanthoastrocytoma in an infant

Pleomorphic xanthoastrocytoma (PXA) is a rare brain tumor and typically occurs in the superficial cerebral hemispheres of young subjects. We report a case of PXA in the cerebellum of a 3-month-old infant in view of its unusual location and age. The patient presented with a 1-month history of upward eyeball gazing difficulty. To the authors' knowledge, this is the first report of occurrence of this neoplasm in the cerebellum of an infant. We report the morphologic and immunophenotypical features, and literature review with regard to the clinicopathologic aspects of a case of unusual PXA.     

Cerebellar pleomorphic xanthoastrocytoma in a patient with neurofibromatosis type 1: a case report and literature review

Pleomorphic xanthoastrocytoma (PXA) is an uncommon tumor of young adults that typically occurs supratentorially. It is generally considered to be a low-grade, circumscribed tumor that when treated by surgical resection has a relatively favorable outcome. Cases of cerebellar PXA are rare, and those associated with neurofibromatosis type 1 (NF1) are even less common, with only 2 cases reported to date. We present herein a third case of PXA-NF1 with unusual features. A 33-year-old woman presented with a history of headache. Her medical and family history was significant for NF1. Brain MRI revealed a 3.4 cm ill-defined lesion with a gyriform enhancing pattern in the left cerebellum, superficially mimicking Lhermitte-Duclos disease. The patient underwent a gross total resection of the lesion and had an unremarkable postoperative course. While the lesion had histological features typical of “pure” PXA (WHO grade II) it had an unusual growth pattern with thickening of the superficial cerebellar folia and predominant leptomeningeal involvement. No BRAF, IDH-1, or IDH-2 mutation was identified. Three months after surgery, local recurrence was detected, and the patient was treated with radiation therapy. One year after the first surgery, she underwent surgical resection of the recurrent/residual tumor. Histologically, the recurrent tumor showed very similar features to the initially resected tumor, with no anaplastic features. Most cerebellar PXAs have an indolent clinical behavior as do most cerebral PXAs. Whether co-existence of NF1 was a factor in altering the clinical course and biologic behavior of this patient’s tumor is currently unknown.     

Cytologic features of pleomorphic xanthoastrocytoma,WHO grade II. A comparative study with glioblastoma

Pleomorphic xanthoastrocytoma (PXA) is a WHO grade II astrocytic tumor of children and young adults. It is characterized by pleomorphic, atypical astrocytes. Atypia is so remarkable, that PXA can be easily misdiagnosed as malignant glioma. If confused with a high‐grade glioma the neurosurgeon may not proceed with a complete resection. Therefore, a specific recognition during intraoperative consultation is particularly important. We describe four cases of PXA evaluated during intraoperative procedures. Findings were compared with those of 22 glioblastomas. PXA smears were moderately cellular and showed a variable population of pleomorphic cells and fibrillary fragments with vessels. Tumoral cells were of intermediate size with a less frequent population of large, atypical cells. Some showed bi/trinucleation with bizarre nuclei. In two cases, tumoral cells with microvacuolization resembling xanthic astrocytes were present. No necrosis, mitotic activity, phagocytic macrophages or apoptotic fragments were seen. Smears from glioblastoma were more cellular than those of PXA with numerous neoplastic cells, branching vessels and myxoid substance. Cellular atypia was evident and mitoses were seen in all cases. Most cases showed an abundant population of accompanying macrophages and cellular debris. Differences between PXA and glioblastoma were related to cell turnover rather than cytomorphologic features. Glioblastoma shows features of high cellular replication showing a dirty background with necrosis and phagocytic macrophages as well as mitotic figures and apoptosis. On the other hand, smears from PXA have a clean background with no necrosis, cellular fragments or relevant mitotic activity. Diagn. Cytopathol. 2017;45:339–344. © 2016 Wiley Periodicals, Inc.     

Clinicopathological study of pleomorphic xanthoastrocytoma: correlation between histological features and prognosis

The correlation between histopathological characteristics and prognosis was studied in six cases of pleomorphic xanthoastrocytomas (PXA) found in five patients. With regard to the duration from onset to the resection of the tumor, and the postoperative course, three cases had a favorable prognosis, although one case fatally recurred and in another, serial CT showed rapid tumor growth for 3 years. The histological characteristics of the favorable group of PXA comprised remarkable degeneration, low mitotic activity and a low MIB-1 labeling index. In contrast, the characteristics of the latter two cases of PXA rarely showed degeneration, had atypical mitoses, increasing mitotic activity and a higher MIB-1 labeling index, which indicates that the findings of degeneration, atypical mitoses, mitotic activity and MIB-1 labeling index correlate with the biological behavior of PXA. However, with regard to histological appearance and clinical course, PXA are tumors with a wide range of biological behavior.     

Complex analysis of a recurrent pleomorphic hyalinizing angiectatic tumor of soft parts

Pleomorphic hyalinizing angiectatic tumor of soft parts is a recently recognized, low-grade mesenchymal neoplasm of uncertain lineage. It is characterized by clusters of ectatic, fibrin-lined, thin-walled vessels surrounded by pleomorphic but mitotically inert spindled cells with frequent intranuclear inclusions and a variable inflammatory component. Here, we report a case of recurrent pleomorphic hyalinizing angiectatic tumor in a 37-year-old white woman. Touch imprint cytologic analysis revealed oval and spindled cells with fine chromatin, occasional prominent intranuclear inclusions, and intracytoplasmic pigment. The histologic features of the cells constituting the bulk of tumor were those characteristic of a putative precursor lesion ("early pleomorphic hyalinizing angiectatic tumor") as well as another recently described entity known as hemosiderotic fibrohistiocytic lipomatous lesion. Cytogenetic analysis revealed 2 unbalanced translocations involving chromosomes 1 and 3 and chromosomes 1 and 10, with a karyotype of 45,XX,der(1)t(1;3)(p31;q12),-3,der(10)t(1;10)(p31;q25)[11]/46,XX[4], thus suggesting that this disease is neoplastic. The controversies in classification of these lesions are also discussed.     

Recurrent copy number alterations in low‐grade and anaplastic pleomorphic xanthoastrocytoma with and without BRAF V600E mutation

Pleomorphic xanthoastrocytoma (PXA) is a rare localized glioma characterized by frequent BRAF V600E mutation and CDKN2A/B deletion. We explored the association of copy‐number variants (CNVs) with BRAF mutations, tumor grade, and patient survival in a cohort of 41 PXA patients using OncoScan chromosomal microarray. Primary resection specimens were available in 38 cases, including 24 PXA and 14 anaplastic PXA (A‐PXA), 23 BRAF V600E mutant tumors (61%). CNVs were identified in all cases and most frequently involved chromosome 9 with homozygous CDKN2A/B deletion (n = 33, 87%), a higher proportion than previously detected by comparative genomic hybridization (50%–60%) (37). CDKN2A/B deletion was present in similar proportion of PXA (83%), A‐PXA (93%), BRAF V600E (87%), and wild‐type (87%) tumors. Whole chromosome gains/losses were frequent, including gains +7 (n = 15), +2 (n = 11), +5 (n = 10), +21 (n = 10), +20 (n = 9), +12 (n = 8), +15 (n = 8), and losses −22 (n = 11), −14 (n = 7), −13 (n = 5). Losses and copy‐neutral loss of heterozygosity were significantly more common in A‐PXA, involving chromosomes 22 (P = 0.009) and 14 (P = 0.03). Amplification of 8p and 12q was identified in a single tumor. Histologic grade was a robust predictor of overall survival (P = 0.003), while other copy‐number changes, including CDKN2A/B deletion, did not show significant association with survival. Distinct histologic patterns of anaplasia included increased mitotic activity in an otherwise classic PXA or associated with small cell, fibrillary, or epithelioid morphology, with loss of SMARCB1 expression in one case. In 10 cases, matched specimens were compared, including A‐PXA with areas of distinct low‐ and high‐grade morphology (n = 2), matched primary/tumor recurrence (n = 7), or both (n = 1). Copy‐number changes on recurrence/anaplastic transformation were complex and highly variable, from nearly identical profiles to numerous copy‐number changes. Overall, we confirm CDKN2A/B deletion as key a feature of PXA not associated with tumor grade or BRAF mutation, but central to the underlying genetics of PXA.     

Pigmented pleomorphic adenoma,a novel melanin-pigmented benign salivary gland tumor

This paper reports a pleomorphic adenoma with grossly visible pigmentation resulting in the macroscopic appearance of melanotic lesion in a 33-year-old Japanese male. In addition to the characteristic histopathological features of a benign pleomorphic adenoma, variously formed and -sized cells, many of which were considered to be melanocytes, containing melanin pigment in their cytoplasm, were distributed in the epithelial component. In addition, melanin pigment was deposited in tumor cells of duct structures. Furthermore, condensed secretory substances with marked pigmentation were frequently seen in the tubular lumina. Perusal of the English language literature revealed only two cases of parenchymal pigmentation of salivary gland tumors: both were mucoepidermoid carcinoma. The possible histogenesis of melanocytes in the salivary gland lesions is discussed, though no firm conclusion could be drawn.     

Pleomorphic xanthoastrocytoma: report of a case with light and electron microscopy

A case of pleomorphic xanthoastrocytoma is reported with light and electron microscopic findings. This unusual tumor arose in a 15-year-old male. The tumor consisted predominantly of nests of xanthomatous cells and plump spindle cells surrounded by a prominent reticulin network. There was considerable cellular pleomorphism with abundant bizarre giant cells and multinucleated cells. Occasional mitoses were present. Electron microscopy and immunoperoxidase localization of glial fibrillary acidic protein (GFAP) confirmed the glial nature of the tumor. Recognition of this tumor is important. Despite its “malignant” appearance, the tumor characteristically has a relatively good prognosis and should not be confused with highgrade gliomas or meningeal sarcomas, which require aggressive therapy.     

A subcutaneous pleomorphic hyalinizing angiectatic tumor of soft parts of the right chest wall: report of a rare case

Pleomorphic hyalinizing angiectatic tumor of the soft parts is an extremely rare mesenchymal tumor consisting of spindled and pleomorphic tumor cells and clusters of ectatic, fibrin-lined vessels. It typically occurs in the subcutaneous tissues of the distal extremities, usually the ankles and feet. Here we present a case of pleomorphic hyalinizing angiectatic tumor of the soft parts of the right chest wall in a 51-year old female. The tumor was subcutaneous, nonencapsulated, and about 2.0 cm×1.0 cm. Microscopically, the tumor was composed of numerous ectatic, fibrin-filled, thin-walled blood vessels, surrounded by spindled or pleomorphic tumor cells arranged in sheet-like or fascicular architecture, or randomly. Mitotic activity of the tumor cells was low. Immunohistochemical analysis shows that the tumor cells were positive for CD34 and vimentin, but negative for CD31, CK, desmin, EMA, HMB45, Myo D1, P63 and S-100. Ki67 index was about 1%.     

The genetic landscape of anaplastic pleomorphic xanthoastrocytoma

Pleomorphic xanthoastrocytoma (PXA) is an astrocytic neoplasm that is typically well circumscribed and can have a relatively favorable prognosis. Tumor progression to anaplastic PXA (WHO grade III), however, is associated with a more aggressive biologic behavior and worse prognosis. The factors that drive anaplastic progression are largely unknown. We performed comprehensive genomic profiling on a set of 23 PXAs from 19 patients, including 15 with anaplastic PXA. Four patients had tumor tissue from multiple recurrences, including two with anaplastic progression. We find that PXAs are genetically defined by the combination of CDKN2A biallelic inactivation and RAF alterations that were present in all 19 cases, most commonly as CDKN2A homozygous deletion and BRAF p.V600E mutation but also occasionally BRAF or RAF1 fusions or other rearrangements. The third most commonly altered gene in anaplastic PXA was TERT, with 47% (7/15) harboring TERT alterations, either gene amplification (n = 2) or promoter hotspot mutation (n = 5). In tumor pairs analyzed before and after anaplastic progression, two had increased copy number alterations and one had TERT promoter mutation at recurrence. Less commonly altered genes included TP53, BCOR, BCORL1, ARID1A, ATRX, PTEN, and BCL6. All PXA in this cohort were IDH and histone H3 wildtype, and did not contain alterations in EGFR. Genetic profiling performed on six regions from the same tumor identified intratumoral genomic heterogeneity, likely reflecting clonal evolution during tumor progression. Overall, anaplastic PXA is characterized by the combination of CDKN2A biallelic inactivation and oncogenic RAF kinase signaling as well as a relatively small number of additional genetic alterations, with the most common being TERT amplification or promoter mutation. These data define a distinct molecular profile for PXA and suggest additional genetic alterations, including TERT, may be associated with anaplastic progression.     

脑多形性黄色瘤型星形细胞瘤的临床病理观察

目的 探讨多形性黄色瘤型星形细胞瘤（PXA）的临床病理特征、诊断及鉴别诊断、治疗及预后。方法 对南京军区南京总医院1980-2004年间6287例中枢神经系统肿瘤中的15例PXA（0．2％）,以及2例会诊病例,进行临床病理学观察,免疫组织化学SP法检测8种抗体的表达：胶质纤维酸性蛋白、波形蛋白、S-100、上皮细胞膜抗原、突触素、神经微丝、CD68及CD34,获得其中10例的随访资料。结果 患者年龄12～55岁,平均30．8岁,男6例,女11例。主要症状为癫痫发作、头痛、头晕等。肿瘤发生于幕上者16例,占94．1％,其中发生于颞叶者7例,占41．2％。肿瘤大小2—7cm,平均4．3cm,9例有囊性变。除2例会诊病例外,全切除12例,次全切除3例。随访10例,生存8例,生存时间10个月- 13年7个月,平均生存6年,生存10年以上者2例。组织学特征为：单核或多核巨怪瘤细胞、梭形细胞和泡沫样瘤细胞混合而成,肿瘤中有丰富的网状纤维及淋巴细胞浸润,缺乏坏死,核分裂象无或少。胶质纤维酸性蛋白、波形蛋白及S-100蛋白免疫组织化学染色均呈弥散阳性表达,CD34阳性率为77％。1例伴有间变特征的PXA,有较多核分裂象（≥5个／10HPF）。2例有脑实质及血管周围间隙的浸润。1例影像学检查提示肿瘤复发及脑膜播散。结论 PXA属WHOII级肿瘤,肿瘤全切除及组织学为典型性PXA者预后较好,少数PXA可复发及间变。瘤细胞巨大、怪异,容易误诊为WHOⅣ级的巨细胞胶质母细胞瘤,两者的鉴别要点在于PXA部分可见泡沫样瘤细胞,核分裂象无或少,缺乏坏死。瘤细胞CD34的阳性表达有助于PXA的诊断。     

Epithelioid variant of pleomorphic liposarcoma: report of a case

A case of an epithelioid variant of pleomorphic liposarcoma (PL) arising in the back of a 72-year old male is presented. The lesion was a well-circumscribed but unencapsulated, yellowish white mass measuring 11 x 10 x 9 cm in the subcutis and muscle. Histologically, the tumor consisted of three elements; an epithelioid cell element occupying about 50%, a lipogenic and mixed lipogenic and epithelioid cell element occupying 40%, and a malignant fibrous histiocytoma-like element. The lipogenic area was composed of uni- and multivacuolated pleomorphic lipoblasts. Immunohistochemically, the tumor was positive for vimentin, epithelial membrane antigen, and CD10. It was negative for desmin, alpha-smooth muscle actin, muscle actin, S-100 protein, and cytokeratins 8 and 18. The epithelioid variant of PL should be differentiated from metastatic renal cell carcinoma and adrenal cortical adenocarcinoma.     

Pleomorphic xanthoastrocytoma: a comparative pathological study between conventional and anaplastic types

Aims:  To facilitate the understanding and correct diagnosis of the anaplastic variant of pleomorphic xanthoastrocytoma (PXA).
Methods and results:  Twelve cases of PXA were divided into six conventional and six anaplastic types. Three anaplastic PXAs developed in recurrent tumours and three occurred as the primary tumour. Anaplastic PXAs were microscopically characterized by monotonous proliferation of atypical cells, increased mitotic activity, necrosis and microvascular proliferation. Characteristic features of conventional PXA are also variously included in all anaplastic PXAs. No remarkable differences were detected in the immunohistochemical profiles including the neuronal phenotype between the conventional and anaplastic types. Ki67 labelling indices of the anaplastic type were significantly higher than those of the conventional type, whereas p53 showed no difference. Immunohistochemical and fluorescence in situ hybridization analyses on epidermal growth factor receptor did not demonstrate overexpression or gene amplification.
Conclusions:  The anaplastic PXA, which occurs de novo or through recurrence, should be distinguished from glioblastoma by identifying the salient microscopic features of conventional PXA even in the anaplastic areas; and by demonstrating the expression of neuronal markers, in that the former is expected to have longer survival.     

Primary pleomorphic rhabdomyosarcoma of the kidney in an adult

Sarcoma of the kidney is uncommon and represents between 1% and 3% of all malignant renal tumors. Primary rhabdomyosarcoma of the kidney in adult age is unusual, and only sporadic cases have been reported. This is a very aggressive tumor with dismal prognosis. We report a new case of pleomorphic rhabdomyosarcoma of the kidney in an adult patient.     

Accumulation of MDM2 in pleomorphic xanthoastrocytomas

The molecular genetic basis and the tumorigenic mechanism of pleomorphic xanthoastrocytoma (PXA) still remain to be elucidated. The amplification of the mdm2 gene and accumulation of the MDM2 protein, which is considered to be one of the major cellular regulators of p53-mediated cell growth control, were studied in eight specimens of PXA obtained from five patients. All of the PXA samples showed at least focal immunopositivity for MDM2. However, none of the samples showed mdm2 gene amplification. These results suggest that accumulation of MDM2 without gene amplification may be one of the major molecular events occurring in the tumorigenesis of PXA.     

Giant cell glioblastoma versus pleomorphic xanthroastrocytoma: a challenging case

Here we present a challenging case originally diagnosed as giant cell glioblastoma WHO grade 4 in a 48-year-old lady with a background of Li-Fraumeni syndrome. After an initial excision and neoadjuvant chemoradiotherapy the patient had a 5 year disease-free period before having a recurrence. The recurrent tumour alongside the original tumour were reviewed. By reviewing the clinical history and disease progression and combining this with improved genetic testing methodologies a reviewed diagnosis of anaplastic pleomorphic xanthoastrocytoma (PXA) WHO Grade 3 was made. This case highlights how many factors can affect a diagnosis and how the clinical course may require for diagnoses to be reviewed and refined.     

肺多形性癌的病理学观察

目的 对１０例肺多形性癌回顾性临床病理研究,探讨肺多形性癌的临床病理特点。方法 采用组织病理学、免疫组织化学ＳＰ法标记（角蛋白、波形蛋白 Ｍａｃ３８７、结蛋白、肌动蛋白、Ｓ－１００蛋白）对１０例肺多形性癌进行研究。结果 肺多形性癌多见于５０岁以上的男性,临床首发症状咳嗽咳痰、咯血或患侧胸痛,镜下以鳞癌、腺癌等成分为主,伴有多少不等的梭形细胞或（和）巨细胞成分。肿瘤的上皮成分表达角蛋白,梭形细胞表达波形蛋白,３例上皮及梭形细胞成分同时表达角蛋白及波形蛋白。结论 肺多形性癌具有多种病理组织形态特征,病理诊断上易与癌肉瘤混淆。明确该肿瘤的组织发生,对于诊断及鉴别诊断有重要意义。     

Benign pleomorphic adenoma arising in a parotid lymph node

Summary A rare case of a benign pleomorphic adenoma is reported, arising in a parotid lymph node in a 52-year-old woman. Serial sections showed that the tumor tissue was surrounded by a mantle of lymphoid tissue which had the essential characteristics of a lymph node. The pathogenesis of the lesion is discussed and the literature is briefly reviewed.