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Atypical spindle cell lipomatous neoplasm, also known as well-differentiated spindle cell liposarcoma, represents a newly discovered entity of adipocytic tumors. Recent research has shown this tumor variant to be more related to spindle cell lipoma, rather than the originally hypothesized atypical lipomatous tumor spectrum. Here we present a case of a 58-year-old man with a history of chronic lymphocytic leukemia with an enlarging mass on the posterior left shoulder, initially hypothesized to be a benign lipoma. However, magnetic resonance imaging showed a large, multiseptated, heterogeneous mass concerning for soft tissue sarcoma. After resection, pathologic analysis showed cells closely resembling spindle cell lipoma, with additional cellular and fascicular zones containing lipoblasts and mitotic figures. Molecular analysis showed no MDM2 amplification. This lack of amplification indicates this tumor is distinctly different from an atypical lipomatous tumor, which characteristically displays MDM2 amplification. However, tumor expression of RB1 was normal. The majority of atypical spindle cell lipomatous neoplasms are associated with RB1 deletions. We conclude that we have a unique example of an atypical spindle cell lipomatous tumor.

Granular Cell Astrocytoma (GCA) is a rare astrocytic brain tumor histologically composed of plump astrocytic cells with abundant eosinophilic granular cytoplasm that exhibits immunoreactivity for GFAP and S100 proteins. It is associated with poor outcome often akin to glioblastoma despite its bland histologic appearance. We report a case of GCA in which neoplastic cells resembled macrophages on intra-operative frozen section and smear. Paraffin sections showed features of a granular cell astrocytoma, WHO grade IV, with diffuse immunohistochemical coexpression of GFAP and S100. No mutation of IDH1 or P53 was identified by immunohistochemistry; however, ATRX loss indicating mutation supported an astrocytic lineage. Additionally, sporadic weak cytoplasmic staining for CD68 and EMA and negative staining for CD163 is likely non-specific due to increased lysosomal activity and does not indicate true histiocytic or epithelial differentiation. We recommend that in the absence of overt high-grade features or admixture with conventional diffuse astrocytoma on intra-operative smear and frozen section, it may be advisable to wait to confirm the diagnosis on paraffin section histology and immunohistochemical stains before proceeding with definitive tumor resection. This diagnostic approach will prevent over-treatment by resection of non-neoplastic mimics of GCA.

Background Polymorphous low-grade neuroepithelial tumor of the young (PLNTY) is a recently recognized epileptogenic neuroepithelial tumor. Despite its distinctiveness, its polymorphous histology and the nature of its oligodendrocyte-like cells remain unclear. Case Description A 30-year-old, right-handed man was diagnosed with intractable epilepsy since 22 years of age. Magnetic resonance imaging revealed T2 signal hyperintensity and corresponding T1 signal hypointensity within the subcortical white matter of the right middle temporal gyrus. Positron emission tomography scan demonstrated hypometabolism in the right anterior temporal region. Electroencephalography and stereo-electroencephalography monitoring localized seizures to the right temporal lobe, allowing the patient to undergo right temporal lobectomy. Histologic sections demonstrated cortical dysplasia, white matter heterotopia, and hippocampal reactive gliosis without neuronal loss. Interestingly, an approximately 6-mm subcortical neoplasm was identified in the temporal lobectomy. It was composed of well-differentiated oligodendroglial-like cells but exhibited mild-to-moderate nuclear variability and pleomorphism, and mild infiltration into the overlying cortex without perineuronal satellitosis. No mitotic activity, microvascular proliferation, or necrosis was identified, and Ki-67 labeling index was less than 1%. The tumor was diffusely CD34 positive with moderate glial fibrillary acidic protein and retained ATRX staining, and demonstrated the presence of the BRAF V600E mutation. The tumor was negative for reticulin condensation, synaptophysin, SMI31, neuronal nuclei immunostains, and both the IDH1 mutation and 1p19q codeletion. Overall histologic findings were most consistent with PLNTY. Conclusions The correct diagnosis of PLNTY and its distinction from closely resembling low-grade neuroepithelial tumors is important. We hope our proposed diagnostic features will aid in its proper diagnosis and management.

Chronic intestinal pseudo-obstruction (CIPO), a rare, debilitating disorder of bowel motility dysfunction, is largely a clinical diagnosis, without any universally accepted diagnostic criteria. Three subgroups are generally acknowledged based on the cell-type affected: enteric visceral myopathy (the most common subgroup), neuropathy, and mesenchymopathy. A fourth subgroup includes abnormalities of neurohormonal peptides. Although immunohistochemical staining is reportedly useful for identifying the mesenchymopathic type, its role in diagnosing enteric visceral myopathy and neuropathy has been fraught with difficulties. We present two cases of chronic intestinal pseudo-obstruction that are clinically and histopathologically suggestive of type III visceral enteric myopathy, aiming to expound upon the diagnostic and pathogenic features. We found that the outer-longitudinal layer of the muscularis propria was more severely affected as compared with the inner circular layer. To investigate the value of this finding, we performed immunostains in the one case in which a paraffin block was available. We found increased peripherin and calretinin immunopositive nerve fibers in the outer layer as compared with inner, but without any significant increase in S-100 positivity or alteration in neuronal morphology of myenteric plexus, a novel finding. This differential staining pattern was completely different from Hirschsprung disease, in which we found rare to absent peripherin and calretinin staining. It is unclear if this increase in the outer layer in visceral myopathy reflects a reactive change or dysfunctional axons. In addition, the history of volvulus in one patient and transmural inflammatory changes in the second raise concerns about the higher propensity of clinical complications secondary to the attenuated outer muscular layer. This study suggests that enteric visceral myopathy has histologic and staining characteristics different from Hirschsprung disease, a finding of diagnostic significance in the differential diagnosis of bowel obstruction. Moreover, these features may have pathogenic value and need further confirmation.

Background Mixed tumors of adenomatous and neuronal cells in the sellar region are an uncommon finding. The origins of these heterogeneous tumors are unknown, and management remains unsettled. We report a very rare case of anterior gray matter pituicytic heterotopia with monomorphic anterior pituitary cells that likely represents a variant of nonsecreting pituitary adenoma neuronal choristoma (PANCH) with no ganglion cells. We also review the current literature for the various clinical presentations of PANCH. Case Description A 49-year-old female complaining of headache, blurred vision, and hair loss was found to have a nonsecretory sellar mass with compression of the optic chiasm on magnetic resonance imaging (MRI). The mass was excised via a transsphenoidal procedure. Histological analysis of tissue sections revealed heterotopic gray matter with reactive gliosis without ganglion cells or Herring bodies. Only 1 smear exhibited characteristics of a pituitary adenoma. Conclusions The overall findings were most consistent with a variant of PANCH. At a postoperative follow-up of 4.5 years, there was resolution of visual symptoms, and the residual sellar mass was stable on MRI. Neuronal choristoma is hypothesized to originate from embryonal pituitary or hypothalamus, or by differentiation from pituitary adenoma cells. Surgery is the cornerstone of management, and the clinical course appears to be similar to that of nonfunctioning pituitary adenoma in reported cases.

Malignant rhabdoid tumors (MRTs) are well recognized in the kidney and extrarenal sites such as soft tissues, retroperitoneum, and bladder but are classified as atypical teratoid/rhabdoid tumors in the central nervous system. The unifying features of both extracranial MRT and atypical teratoid/rhabdoid tumors are the exon deletions/mutations of the SMARCB1 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily b, member 1) gene in 22q11.23 and resulting loss of SMARCB1/INI1 (integrase interactor 1) protein expression by immunohistochemistry. We herein report a case of extrarenal rhabdoid tumor confined to the bladder in a 3-year-old child, diagnosed by histopathology and confirmed by immunohistochemical and molecular studies. This is only the fourth molecularly proven primary MRT of the bladder to be reported. The patient’s peripheral blood was negative for the deletions observed in the tumor, thereby confirming a sporadic origin for the tumor. Given the possible dismal outcome, urgency for definitive diagnosis to institute intensive multimodality therapy, histopathologic differential diagnosis with rhabdomyosarcoma and urothelial carcinoma with rhabdoid features, and lack of consensus management guidelines, oncologists, urologists, and pathologists must be aware of this entity. Evaluation for a germ line SMARCB1 alteration may greatly aid risk stratification and family planning.

Invasive micropapillary carcinomas (IMC) and metaplastic breast carcinoma (MBC) have different clinicopathologic features. This study reports an unusual case of multifocal grade III IMC associated with MBC component in a 35-year-old woman. MBC was vimentin positive, pancytokeratin negative, and showed focal p63 positivity. Immunostains for estrogen and progesterone receptor, and fluorescence in situ hybridization for Her2/neu amplification were negative. All the left axillary lymph nodes dissected were positive for metastatic carcinoma with ductal and IMC patterns, but without metaplastic component. Postmastectomy computed tomography and magnetic resonance imaging scans showed metastases to lungs, liver, brain, and vertebrae. The biologic behavior of tumor was in accordance with histology, so that the nodal and distant metastases were testament to the underlying inherently aggressive IMC, whereas large tumor size and triple negativity reflected the features of MBC. To the best of the authors’ knowledge, this is the first report of a metaplastic variant of invasive micropapillary breast carcinoma with triple negative phenotype.

Mycoplasma pneumoniae is a well-known cause of atypical pneumonia. CNS involvement is a relatively frequent extrapulmonary manifestation, most commonly manifesting as encephalitis in the pediatric population. We present two unusual cases of M. pneumoniae encephalitis that presented with symptoms and imaging findings suggesting mass occupying lesions, and worsening altered mental status. Biopsy of the lesions was necessary in both cases to aid with diagnosis. Histopathologic features excluded neoplasm, and established the diagnosis of encephalitis, but did not point toward its etiology. The only finding that indicated M. pneumoniae as the most likely pathogen was serum IgM positivity in the absence of any other identifiable infectious source, and complete neurologic recovery following specific anti-mycoplasmal treatment. The patients were successfully treated with antibiotics and steroids, with the second case also requiring intravenous immunoglobulin and anti-epileptics. The clinical presentation and histopathologic findings suggested an immune-mediated pathogenesis, but acute disseminated encephalomyelitis was excluded due to extensive gray matter involvement. Disease resolution despite status epilepticus and herniation in case 2 is a novel finding of the study. Current principles of diagnosis and management of encephalitis as the presenting manifestation of mycoplasmal infection are discussed.

Dysembryoplastic neuroepithelial tumor (DNT) is commonly located in the supratentorial cortex. Extracortical localization of DNT is extremely rare. A 15-year-old female presented with loss of consciousness after head trauma. MRI demonstrated hydrocephalus secondary to a small non-enhancing T1 hypointense and T2 hyperintense mass lesion in the foramen of Monro; with radiologic impression of low-grade astrocytoma or colloid cyst. Tumor was gross totally resected. Histologic examination showed partly microcystic architecture with oligodendroglia-like neurocytic cells, glioneuronal element, and floating neurons, with synaptophysin reactivity mainly in cell processes, consistent with DNT. Focal subependymoma-like pattern was noted. The low tumor cellularity and morphologic pattern did not support a central neurocytoma. Patient was asymptomatic and was radiologically stable 9 months post-surgery. Literature review of previously reported supratentorial extracortical DNT cases demonstrate that 24 of 25 cases involved the ventricular system (as in our case) of which eight additionally involved periventricular deep gray or white matter. None of the cases recurred following surgery. Clinico-pathologically, extracortical DNTs were similar to the cerebral cortical simple DNTs and differed only in their presentation related to their location. The novel aspects of this report are the radiologic resemblance of DNT to colloid cyst and focal subependymoma-like pattern on histology. Importantly, intra-/periventricular region appears to be the most common extracortical location of cerebral DNT with a 100% disease-free survival reported in the literature.

Spinal cord tumors in pediatric patients are rare, representing less than 1% of all central nervous system tumors. Two cases of pediatric primary intramedullary spinal cord glioblastoma at ages 14 and 8 years are reported. Both patients presented with rapid onset paraparesis and quadraparesis. Magnetic resonance imaging in both showed heterogeneously enhancing solitary mass lesions localized to lower cervical and upper thoracic spinal cord parenchyma. Histopathologic diagnosis was glioblastoma. Case #1 had a small cell component (primitive neuroectodermal tumor-like areas), higher Ki67, and p53 labeling indices, and a relatively stable karyotype with only minimal single copy losses involving regions: Chr8;pter-30480019, Chr16;pter-29754532, Chr16;56160245–88668979, and Chr19;32848902-qter on retrospective comparative genomic hybridization using formalin-fixed, paraffin-embedded samples. Case #2 had relatively bland histomorphology and negligible p53 immunoreactivity. Both underwent multimodal therapy including gross total resection, postoperative radiation and chemotherapy. However, there was no significant improvement in neurological deficits, and overall survival in both cases was 14 months. This report highlights the broad histological spectrum and poor overall survival despite multi modality therapy. The finding of relatively unique genotypic abnormalities resembling pediatric embryonal tumors in one case may highlight the value of genome-wide profiling in development of effective therapy. The differences in management with intracranial and low-grade spinal cord gliomas and current management issues are discussed.

The current WHO 2007 classification divides meningiomas into a 3-grade prognostic hierarchy. Recent literature evokes two pathways to disease progression in meningiomas akin to a comparable paradigm in gliomas, but without similar prognostic connotation: de novo anaplastic meningioma (better prognosis), and transformed meningioma (worse prognosis). We present two adult cases of transformed meningiomas that display a spectrum of morphologic progression. Case 1 at presentation showed a random admixture of meningothelial, atypical and anaplastic meningioma. The tumor recurred as anaplastic meningioma. Case 2 presented as a chordoid meningioma, but recurred as anaplastic meningioma mainly at the invasive front in transition with residual chordoid pattern. Of interest, portions of tumor also showed papillary configuration. In accordance with the dire prognosis for anaplastic meningioma, both patients succumbed to their disease within 2 months of recurrence. The present study highlights two main points: First, that proper recognition of focal high-grade areas in a heterogeneous low-grade meningioma (case 1) provides critical morphologic clues to spatial histologic progression and predicts aggressive biologic behavior, as evidenced by progression to frankly anaplastic meningioma at recurrence. Second, the presence of papillary in addition to anaplastic areas, in the recurrence of a previously diagnosed chordoid meningioma supports the ostensibly heightened transforming potential of grade II meningiomas, but also reflects on the morphologic heterogeneity of high-grade meningiomas, and their potentially diverse pathways of progression. We propose that grading of meningiomas as outlined by WHO is of more critical prognostic import than histologic sub-typing, and must include a thorough survey of the tumor-brain interface. Future molecular genetic correlates, akin to those characterized in gliomas, could help stratify prognostic subcategories to refine meningioma grading, and govern optimal therapeutic strategies.

Nonround cell tumors are rare in children and often difficult to diagnose. This article describes an 18-month-old child who presented with a mass on the outer aspect of the left eyelid. This mass was incompletely excised. Histologically, the tumor had nests of basaloid and relatively round cells with immature acinar or ductular structures similar to those seen in a conventional sialoblastoma, but these nests were embedded in a malignant spindle cell stroma. This stroma on immunohistochemistry was marked with S-100 and cytokeratin, which, in combination with the pertinent ultrastructural evidence, indicated a myoepithelial differentiation. Overall histologic features suggested a tumor similar to a sialoblastoma with sarcomatoid transformation of the myoepithelial component, hitherto not described in literature. This tumor probably arose from the palpebral lobe of the lacrimal gland. Postsurgery, the patient received chemotherapy (6 cycles of ifosfamide, vincristine, and doxorubicin hydrochloride [Adriamycin]) and local radiotherapy in view of residual disease. Three months after completion of the treatment (1 year after surgery), the patient is well, without any local disease. Awareness of this unusual histology of sialoblastoma will help in avoiding misdiagnosis and also refine treatment-related issues on this rare tumor.

Proteus syndrome is a rare disorder of asymmetric overgrowth of various tissues of the body and is associated with specific tumors appearing before the second decade. Although there have been reports of lesions of the genitourinary tract associated with Proteus syndrome, a case of serous borderline tumor of the paratestis has not been previously recorded. We report the first such case in a 20-month-old child who presented with a left-sided testicular mass that was found on histology to be a serous borderline tumor of the paratestis. Surgical management included a left inguinal radical orchiectomy and surveillance follow-up.

Central neurocytomas (CN) are uncommon tumors of the central nervous system, most descriptions of which available in the literature are in the form of isolated case reports and small series. Owing to this rare incidence, diagnosis and management of this neoplasm remain controversial. Usually, these tumors affect lateral ventricles of young adults and display characteristic neuroimaging and histomorphologic findings. Neurocytomas often mimic oligodendrogliomas when confirmation of diagnosis rests on immunohistochemistry, ultrastructure, and genetic studies. Extraventricular neurocytomas, situated entirely within the brain parenchyma and spinal cord, have also been reported. Typically, CN are associated with a favorable outcome although cases with more aggressive clinical course with recurrences are not unknown. MIB-1 labeling index (LI) of >2% often heralds poor prognosis and tumour recurrence. Safe maximal resection is presently considered the ideal therapeutic option, with best long-term prognosis in terms of local control and survival. The role of adjuvant radiotherapy apparently seems to benefit patients with incomplete resection and in atypical neurocytoma. Utility of other therapeutic regimen, however, remains shrouded in controversy. Epidemiology, histogenesis, clinical profile, histology, neuroimaging and therapeutic modalities of neurocytomas have been comprehensively reviewed, with special emphasis on CN and extraventricular neurocytomas and their atypical counterparts.

Most central neurocytomas (CN) and spinal neurocytomas (SN) have a bland well-differentiated histologic picture and uneventful clinical course. However, rare examples showing histologic atypia, recurrence and even CSF dissemination have been reported. Herein we report a case of recurrent spinal neurocytoma in a 24-year-old male who presented with a 2-month history of weakness and numbness of the left upper and lower limbs, and was previously operated at the same site 10 months ago. MRI revealed a contrast enhancing intramedullary mass involving C5-T1 region. Radiologic and operative impression at both surgeries was that of a glioma, possibly anaplastic. Histologic and immunohistochemical features in both resections were those of an atypical neurocytoma. The tumor showed rare mitoses, focal mild vascular proliferation in both specimens, and necrosis in the initial specimen. MIB1 labeling indices were 9 and 10%, respectively. Based on the analysis of this case and limited data from the literature, it is hypothesized that SN shows a histopathologic picture, immunoprofile and biologic behavior very similar to CN. However, the presence of histologic atypia and increased MIB1 index in SN appear to more closely correlate with tumor recurrence and a worse overall outcome, in part due to their location in the critical region of cervical spinal cord. Therefore, we hypothesize that SN with atypia requires a close clinical follow up. As in CN, radiation therapy is perhaps best reserved for atypical, progressive and recurrent SN.

Lymphangioleiomyomatosis (lymphangiomyomatosis [LAM]), a rare disease of unknown etiology that is seen only in women usually in the reproductive period, generally presents with features of pulmonary involvement. Extrapulmonary involvement, such as angiomyolipomas and retroperitoneal adenopathy, can occur in up to 75% of cases. It is very rare, however, for patients to present with features of extrapulmonary LAM. We present an unusual, localized case of LAM presenting with neurologic symptoms related to a retroperitoneal mass in a 51-year-old woman. Magnetic resonance imaging showed that the mass involved retroperitoneal lymph nodes, and a clinical diagnosis of atypical sarcoma (possibly from a uterine primary) was made. The mass was resected, and a total abdominal hysterectomy was performed. On pathologic examination, the mass showed classic histologic features of LAM with spread along lymphatic channels in the lymph nodes. Intralymphatic projections simulated lymphatic metastasis; however, the cytologic features were benign. Immunostains revealed the tumor to be positive for smooth muscle actin and desmin, but negative for HMB-45. The uterus was unremarkable, except for a subserosal leiomyoma. Although intratumoral variability for HMB-45 has recently been described, to the best of our knowledge, this is the first documented case of HMB-45–negative, histologically classic LAM. Because of the presence of several atypical features in this case, such as age, location, compressive neurologic presentation, radiologic impression of atypical sarcoma, and HMB-45 negativity, we feel that this case may represent a distinct, as yet uncharacterized variant of LAM.

Adenocarcinomas metastatic to brain from lung or colon may pose differentiation difficulties. Ultrastructurally, both may have brush borders with rootlets. This study examines the ultrastructural morphology and immunohistochemical expression of villin (associated with rootlets), cytokeratin 7 (present in lung adenocarcinomas), and cytokeratin 20 (present in colon adenocarcinomas) in 19 formalin-fixed sequential surgical biopsies of lung adenocarcinomas metastatic to brain as compared to 13 colonic adenocarcinoma metastases. Of lung tumor metastases, mucinous differentiation with rootlets was most common [6/19(32%)]. All colon tumor metastases were cytokeratin 7(-), 20(+), and profusely villin(+). Well-formed rootlets were seen. All lung metastases were cytokeratin 7(+) and 20(-). 5/6(83%) lung metastases with rootlets were focally villin(+). 12/13(95%) without rootlets were villin(-). Rootlets are extremely common in lung adenocarcinoma metastatic to brain. Villin immunoreactivity closely correlates with rootlets. Its distribution is a useful adjunct to cytokeratin 7 and 20 in differentiation of lung versus colon adenocarcinomas metastatic to the brain.

OBJECTIVE: To review the cytomorphologic features of adrenocortical carcinoma (ACC), correlate them with histology and compare them with the cytomorphologic features of very similar renal cell carcinoma (RCC) on fine needle aspiration (FNA) smears. STUDY DESIGN: Cytomorphologic features in 7 cases of ACC in FNA smears were analyzed and compared with those in 10 cases of RCC. Five cases of ACC and five of RCC were later confirmed on histopathology. Parameters analyzed pertained mainly to architectural, cytoplasmic and nuclear features. RESULTS: The presence of cells in sheets with a central, thin-walled vascular core (endocrine vascular pattern); monomorphic cell population ; eccentric nuclei; focal dramatic anisonucleosis; and focal spindling with crushing was a prominent feature of ACC in contrast to RCC, which showed mainly an acinar pattern with only a focal endocrine pattern, well-defined cytoplasmic angles and projections, and cytoplasmic vacuolations; pleomorphism, if present, was gradual and seen uniformly in all the cells. Univariate analysis using the X 2 test showed the presence of endocrine architecture; focal dramatic anisonucleosis; crushed spindle fragments; eccentric nuclei; and absence of cytoplasmic vacuolizations as significant differentiating features in favor of ACC (P

A cutaneous ciliated cyst is a rare entity found predominantly in the lower extremities and perineal region of young females. Although initially described by Hess in 1890, the present day term, “cutaneous ciliated cyst,” was proposed by Farmer in 1978 and includes a wide array of cyst types. Despite their typical female predominance and location, many have described cutaneous ciliated cysts in males and atypical locations. In addition, Mullerian cysts in the posterior mediastinum and the retroperitoneum have been reported. To date, only 40 cases have been reported in the literature of a Mullerian-type, cutaneous ciliated cyst. Here, we report a case of 13-year-old female with one in the gluteal cleft, initially presenting as a pilonidal cyst. We also discuss the differential diagnosis of pediatric sacrococcygeal lesions and pathogenesis of a Mullerian-type, cutaneous ciliated cyst.

Forty three cases of astrocytic tumors and mixed gliomas were studied with the aim of evaluating the reproducibility of the Kernohan grading system vis a vis (a) grading using computer-aided malignancy classifier TESTAST 268 and (b) grading by quantitative morphometric evaluation of the various histological parameters of TESTAST 268. These patients were then followed up for variable periods with a maximum of forty months. High inter and intra-observer variability were observed in the Kernohan grading system. TESTAST 268 was found to be simpler, rapid and more reproducible. However, one drawback observed of this system was that it did not completely eliminate inter-observer variability because there was still some subjectivity in assignment of the categorical values against the histological features. Morphometric evaluation of the semi-quantitative assignment values of the 4 histological variables in the TESTAST 268 classifier using Zeiss Morphomat-30 revealed a statistically significant difference between the clusters of the measured quantitative values. A repeat grading using TESTAST 268 and categorical assignment values of histological features derived from the absolute values obtained by morphometry resulted in complete elimination of inter-observer variability. Thus, this study highlights the importance of objectivisation using TESTAST 268 and histologic morphometry in the grading of gliomas. However, since this is a preliminary study on a small number of cases, no cut off values of these measurements have been proposed.

Summary Osteopontin ( SPP1 ) is reportedly the most up-regulated gene in primary central nervous system lymphoma (PCNSL). Our objective was to confirm immunoexpression of osteopontin and determine if CD44v6 and CD44H played a significant role as receptors for osteopontin in PCNSL. Twenty PCNSL, 12 nodal diffuse large B-cell lymphoma (N-DLBCL), and 17 extra-nodal DLBCL (EN-DLBCL) archival pathology cases were examined. Osteopontin nuclear positivity was observed in 20 (100%) of 20 PCNSL cases, 16 (95 %) of 17 EN-DLBCL, and 3 of 12 (25%) N-DLBCL. The immunohistochemical score of osteopontin in PCNSL (7.0 ± 3.5) and EN-DLBCL (4.4 ± 4.1) was significantly higher than N-DLBCL (0.3 ± 0.6). Sixteen cases were positive for CD44v6 (33%), including 6 PCNSL, and 5 each EN-DLBCL and N-DLBCL; no statistical difference was observed. CD44H was positive in all cases except one PCNSL but without any significant differences across the 3 groups. CD44H expression was significantly higher in non–germinal center B-cell (GCB) (score 12 ± 1.5) as compared to the GCB group (9.5 ± 3.1), and in non-GCB PCNSL (7.9 ± 4.2) as compared to non-GCB non-CNS lymphoma (2.8 ± 4.0) ( P = .009); the differences were insignificant for osteopontin and CD44v6. Neither CD44H nor CD44v6 scores correlated with the osteopontin expression score or Ki-67 index. Osteopontin immunoexpression was highest in PCNSL, suggesting its probable role in its pathogenesis. However, its lack of correlation with CD44v6 excludes the latter as the likely osteopontin receptor in PCNSL. The significantly higher CD44H expression in the non-GCB than GCB group may contribute to the aggressiveness of the non-GCB DLBCL. Further studies are needed to elucidate the pathway and the prognostic/predictive role of osteopontin in PCNSL.

Most mesenchymal neoplasms of the gastrointestinal tract are currently classified as gastrointestinal stromal tumors (GIST). Gastrointestinal stromal tumors are diagnosed by immunopositivity for CD117, CD34, and DOG1.1, with or without molecular analyses. According to the World Health Organization classification, the diagnosis of primary leiomyosarcomas of the gastrointestinal tract is so rare that there are no significant data on demographic, clinical, or gross features of this tumor. A comprehensive literature search was performed to identify gastrointestinal leiomyosarcomas. Searches were limited to the past 12 years because definitive tools to differentiate leiomyosarcomas from GIST were introduced in the late 1990s. Cases were included only if convincing data were presented. Six cases of esophageal leiomyosarcoma and 5 cases of gastric leiomyosarcoma were confirmed. Furthermore, 26 cases of leiomyosarcoma of the small bowel, 11 cases of the colon, and 8 cases arising in the rectum were identified. Finally, 28 cases of infantile and adolescent leiomyosarcoma were reviewed. Although survival analysis is precluded by small case numbers and limited survival data availability, the trend identifies that increased size and mitotic activity portends to a worse prognosis in small bowel leiomyosarcomas. Colonic leiomyosarcomas appear to be aggressive tumors, regardless of tumor size and mitotic activity. Rectal leiomyosarcomas present as smaller tumors with favorable prognosis. Leiomyosarcomas in post-GIST era are rare tumors of the gastrointestinal tract with distinctive clinicopathologic characteristics. Owing to different treatment options, it is necessary to accurately differentiate these from GIST, using a combination of histologic appearance, presence of smooth muscle antigens, and absence of specific GIST immunomarkers.

Glioblastomas (GBM) are rare in children, but reportedly have more varied outcome which suggests differences in tumor etiology compared to typical GBM of adults. To investigate this we performed high resolution array comparative genomic hybridization (aCGH) analysis on three pediatric infratentorial GBM, ages 3.5, 7 and 14 years. Two of these tumors occurred in the brainstem and one in the spinal cord. While histologically typical, one brainstem tumor showed mainly pleomorphic astrocytic cells, whereas the other brainstem and spinal tumors showed a GFAP positive small cell component. Whole chromosomal gains (#1 and #2) and loss (#20) were seen only in the pleomorphic brainstem GBM, which also showed a high level of segmental genomic copy number changes. Segmental loss involving chromosome 8 was seen in all three tumors (Chr8;133039446-136869494, Chr8;pter-3581577, and Chr8;pter-30480019 respectively), whereas loss involving chromosome 16 was seen in only 2 cases with small cell components (Chr16;31827239-qter and Chr16;pter-29754532). Segmental gain of chromosome 7 was shared only between the 2 brainstem cases (Chr7;17187166-qter and Chr7;69824947-qter). Chromosome 17 showed segmental gain of 17q in the backdrop of loss of 17p only in case 1. Segmental gain of chromosome 1q was seen only in case 2. The spinal GBM showed a relatively stable karyotype with a unique loss of Chr19;32848902-qter. None of the frequent losses, gains and amplifications known to occur in adult GBM were identified, suggesting that pediatric infratentorial glioblastomas show a molecular karyotype that was more characteristic of pediatric embryonal tumors than adult GBM.

Fibrous cortical defect, also known as metaphyseal fibrous defect and nonossifying fibroma, among other terms, is a benign, non-neoplastic proliferative process that is relatively common in the long bones of skeletally immature adolescents. Although the lesion is thought to be a developmental abnormality or defect, the exact etiopathogenesis is largely unknown. The lesion has a limited growth potential and good treatment outcome. This process is very rare in the gnathic bones, and only a few sporadic case reports are documented. This article presents the clinicopathologic features of 2 additional cases and reviews the relevant literature in attempt to identify key features and facilitate rendering definitive diagnosis for this rare entity.

Background: There is no universally accepted staging system for primary brain tumors wherein prognostication is mainly based on complex composite indices . Aim: To develop a simple, pragmatic, and widely applicable grouping/staging system for gliomas, the most common primary brain tumor. Materials and Methods: An expert neurooncology panel with representation from radiation oncology, neurosurgery, pathology, radiology, and medical oncology had several rounds of discussion on issues pertinent to brain tumor staging. The trade off was between the accuracy of prognostic categorization and a pragmatic, widely applicable approach. Results and Recommendations: The Tumor-Node-Metastasis staging was considered irrelevant for gliomas that seldom metastasize to lymphatics or outside the neuraxis. Instead, a 4-point staging/grouping system is proposed, using histological grade as the main prognostic variable and at least one stage migration based on other unfavorable features such as tumor location (brainstem); age ( 50 years for high-grade, and >40 years for low-grade gliomas); poor neurological performance status (NPS 2-4); multicentricity and/or gliomatosis; and adverse biological parameters (proliferative index, angiogenesis markers, apoptotic index, cytogenetic abnormalities, and molecular markers). Conclusion: In absence of a grouping/staging system for primary brain tumors, prognostification is mostly based on complex composite indices. The proposed clinicopathobiological grouping/staging system for gliomas is a simple, pragmatic, and user-friendly tool with a potential to fulfill the objectives of staging classification.

This paper reviews the histomorphological aspects of angiogenesis and neoangiogenesis, quantitative and qualitative, and their applications in prognostic evaluation of neoplastic diseases. The merits and weak points of intratumoral microvessel density (MVD), a widely regarded bona fide predictor of tumour growth, metastases and patient survival, are discussed. Total microvascular area (TVA) has been found useful in recent prognostic studies utilizing newer immunohistochemical vascular markers. Of particular significance is the fact that MVD and TVA are most predictive of patient outcome in those tumours that induce significant neoangiogenesis, namely carcinomas of breast and prostate, and haematological malignancies. In contrast, carcinomas of lung and urinary bladder do not show significant associations of MVD and TVA with poor prognosis, reflecting differences in angiogenic mechanisms. In gliomas, MVD appears to correlate with outcome in high-grade, but not low-grade tumours, and does not correlate with tumour cellularity in the infiltrating portions of the tumour, reflecting a paucity of neoangiogenesis and directional vascular growth. Recent studies have found CD105, Tie-2/Tek and vascular endothelial growth factor receptors to be the best markers of neoangiogenesis. The vascular parameters so measured correlate better with overall and disease-free survival in breast, colon and lung carcinoma than panendothelial markers such as CD31. A correlation of vascular patterns with prognosis has been established in ocular melanomas, glioblastomas and squamous carcinomas of head and neck region. Vascular networks with closed loops are closely associated with mortality due to metastases in uveal melanomas. Fewer bizarre glomeruloid vessels and prominent classical capillary pattern was an independent predictor of longer survival in glioblastoma. Therefore a judicious combination of quantitative and qualitative microscopic angiogenic parameters, with emphasis on neoangiogenesis and vascular patterns wherever applicable, should be an integral component of a more consistent tumour staging system for accurate prognostic evaluation of tumours, selection of optimal anti-angiogenic therapy and pertinent research.

Poorly differentiated thyroid carcinomas with follicular cell phenotype are not well defined. Different diagnostic criteria have been employed for these tumors, including solid growth, nodular, trabecular, and insular patterns. Cytologic features, such as a predominance of tall and columnar cells, have been considered to be diagnostic of poorly differentiated carcinoma. However, there is no agreement among surgical pathologists regarding morphologic criteria for poorly differentiated thyroid carcinoma. We report two unique thyroid neoplasms that we interpreted as poorly differentiated follicular carcinomas. Nodular, trabecular, and sheetlike patterns predominated in both tumors. They were composed of cells that were focally immunoreactive for thyroglobulin and had large vesicular nuclei with prominent nucleoli. A variable number of cells showed rhabdoid phenotype. The rhabdoid inclusions did not stain for thyroglobulin but contained whorls of intermediate filaments that were vimentin positive. There were foci of necrosis and numerous mitotic figures. Both patients were adults and died with multiple pulmonary metastases. The presence of rhabdoid cells in poorly differentiated follicular carcinomas broadens the spectrum of tumors with rhabdoid phenotype. More cases are needed to determine whether the rhabdoid phenotype is a marker for poorly differentiated follicular carcinoma as well as an independent adverse prognostic factor.

An in vivo bromodeoxyuridine (BrdU) labeling index (LI) was estimated in 43 cases of astrocytic tumors and mixed gliomas by one hour intra-operative intravenous infusion at a dose of 200 mg/m2 and correlated with (a) histological grading using a computer aided malignancy classifier TESTAST-268; and (b) histological typing using WHO classification. The lowest BrdU LI was seen in pilocytic and gemistocytic astrocytomas followed by astrocytomas, anaplastic astrocytomas and glioblastoma multiforme in that order. Mixed oligoastrocytomas followed the pattern of their astrocytic counterparts. Tumors of similar histological type showed different BrdU LI values especially amongst astrocytomas and glioblastomas. A statistically significant difference in the BrdU LI was also noted between the higher TESTAST grades of astrocytomas (T III and IV) versus the lower TESTAST grades (T II). Unlike earlier reports in literature, in the present study the category of BrdU LI of1 contained no case of anaplastic astrocytoma or glioblastoma multiforme (TESTAST grades III and IV). Likewise, the category of BrdU LI5 contained only anaplastic astrocytoma and glioblastoma multiforme (TESTAST grades III and IV). Maximum spread of cases was seen in the BrdU LI category of 1-5, not only in terms of histological types but also TESTAST grades. Thus there appeared to be a positive trend of increasing BrdU LI values both with histological types and increasing TESTAST grades. Further, an interesting observation was that by using a combination of TESTAST grades and BrdU LI, the histologically homogenous glioblastoma group could be further subdivided into 4 categories which showed a trend towards prognostic correlation. Thus, this study though preliminary with number of cases being small in some groups, highlights the possible usefulness of combined histological typing, TESTAST grading and in vivo BrdU LI for prognostication of gliomas especially glioblastoma multiforme.

Objective and importance Mycosis fungoides is a rare T-cell lymphoma of the skin that can, in one-half to three-quarters of patients suffering from this disease, involve the viscera in late stages of the disease. Although autopsy series performed more than 2 decades ago showed that the incidence of metastatic mycosis fungoides to the central nervous system is approximately one of seven, a total of only several dozen cases have been reported to date. As compared to meningeal involvement, intraparenchymal metastases are even rarer. We describe a biopsy-proven case of intraparenchymal central nervous system mycosis fungoides in a patient with nonprogressive skin involvement and no detectable visceral involvement, and we present a review of the relevant literature. Clinical presentation A 68-year-old man, 3 years after the diagnosis of his skin disease, developed fatigue, confusion, and frontal lobe signs without the presence of cerebriform cells in the peripheral blood or any other clinical evidence of visceral involvement. Magnetic resonance imaging revealed a diffuse area of increased T2-weighted signal involving the white matter of both cerebral hemispheres as well as a focal area of T2 abnormality along the body of the corpus callosum. The radiological differential diagnosis was either leukodystrophy caused by chemotherapy, progressive multifocal leukoencephalopathy, or glioma with associated white matter changes. Intervention A stereotactic serial brain biopsy revealed diffuse perivascular infiltrates of atypical lymphocytes, as well as several large cells with cerebriform nuclei consistent with mycosis fungoides. The cells were immunoreactive for LCA, MT1, UCHL1, and CD3. Conclusion We stress the importance of including mycosis fungoides as part of the differential diagnosis for a brain lesion in patients with cutaneous T-cell lymphoma, because treatments do exist, and we conclude that a serial stereotactic biopsy may be necessary to provide a definitive diagnosis.

BACKGROUND Intraparenchymal nerve sheath tumors of the central nervous system are rare, usually benign tumors. Three cases with tumor recurrences have previously been reported in the literature. The authors report a case of a malignant intracerebral nerve sheath tumor in a girl age 8 years and analyze the biologic characteristics of this tumor. METHODS The tumor was analyzed by histologic, immunohistochemical, and ultrastructural techniques. RESULTS Magnetic resonance imaging revealed a mixed, attenuating, contrast-enhancing mass in the right posterior temporal lobe. Histopathology of the resected specimen revealed a uniformly S-100 positive and reticulin rich biphasic tumor with a characteristic distribution of spindle and epithelioid cells, with the latter almost entirely confined to the invading edge of the tumor. There was extensive brain infiltration in the form of lobules and fingerlike processes with a targetoid appearance. The spindle cells showed palisading and had elongated, wavy nuclei. Electron microscopy demonstrated basal lamina around both cell types with scattered Luse bodies in between. The patient is perfectly healthy and recurrence free 17 months after surgery. CONCLUSIONS This represents the fourth and the youngest case in the literature of a malignant intracerebral nerve sheath tumor and highlights the distinctive clinicopathologic features of these tumors. First, these tumors have very great infiltrative potential, as observed histopathologically and reflected in their frequent recurrences. Second, epithelioid cells confined to the infiltrative edge suggest their aggressive role. Epithelioid cells have been shown to represent a malignant component of systemic schwannomas with malignant transformation; however, this case does not have any evidence of origin from a preexisting benign schwannoma. Third, despite histologic similarities to neuraxial desmoplastic neuroepithelial tumors, none of the malignant schwannomas had any evidence of divergent differentiation towards astrocytic or neuronal lineage, and had a much worse prognosis. Fourth, the event free survival after initial resection appears to be an important predictor of overall survival in the reviewed cases. Chemotherapy and radiation therapy have not been successful in the treatment of this rare entity. Hence, an accurate diagnosis and planned extensive resection appear to be the key elements in its management. Cancer 1998;82:545-52. © 1998 American Cancer Society.

Extra gonadal germ cell tumours (EGGCT) in women are rare. We report here two such patients. The clinical and laboratory features were — young age, 25 and 22 years, midline location (mediastinum, scalp), elevated tumour marker and normal ovaries on CAT scan. The histological subtype was embryonal carcinoma in both cases. Complete response (CR) was achieved with cisplatin based chemotherapy (CT). Both patients had return of normal ovarian functions and have delivered normal babies (1st patient one, 2nd patient 2 babies). Both remain asymptomatic and disease-free at 30 + and 55 + months follow-up. We conclude that patients with EGGCT after treatment with cisplatin based CT achieve CR with return of normal ovarian functions and prolonged survival.

Intraoperative consultations may pose considerable diagnostic challenge to the neuropathologist in diagnosing primary and metastatic neoplasms of the central nervous system (CNS). Cytological preparations in the form of squash, touch, imprint or smears are few of the available modalities in addition to the frozen section (FS). Although the latter is superior in providing both histologic patterns and cytomorphologic details yet smears are of vital importance when tissue available is limited (stereotactic biopsy), scrutinisation of intercellular matrix (astrocytoma versus oligodendroglioma) and evaluation of discohesive cells (lymphoma, pituitary adenoma) and in inflammatory lesions. This review is intended to emphasize the value, applicability and limitations of neurocytology aiming to expedite the intraoperative smear-based diagnoses of CNS neoplasia as per the World Health Organization (WHO) classification. We recommend that whenever possible, both smears and FS should be examined concomitantly and in a correlative manner. In the unlikely event of a mismatch between the findings on smear and FS, intraoperative diagnosis is primarily based on FS, if adequate tissue is available. However, each case must be evaluated on its own merit and in difficult cases relevant differential diagnoses should be offered to facilitate surgical decisions and optimally triage patient management.

A 52-year-old woman presented with headaches, difficulty with word finding and left eye blindness. MRI showed enhancing frontal dural-based masses suggestive of meningiomatosis. Biopsy and debulking revealed necrotising granulomas, without discernible micro-organisms or neoplasia; a thorough clinical work-up was negative for infection and vasculitis. A CT scan showed mild bilateral hilar lymphadenopathy, a tiny pulmonary nodule and cirrhotic liver. Her subsequent alteration of mental status was attributed to hepatic encephalopathy based upon elevated aminotransferase and ammonia levels, biopsy evidence of hepatoportal sclerosis with rare granulomas and response to lactulose. A diagnosis of neurosarcoidosis of the necrotising sarcoid granulomatosis variant (NS-NSG) with atypical systemic involvement was made. This is the fifth case report of NS-NSG clinically mimicking a neoplasm and histologically mimicking a mycobacterial infection. NS-NSG can have an atypical clinical picture including intracranial masses; a thorough work-up to exclude infectious and other non-infectious aetiologies is a prerequisite to its diagnosis.