Granulomatous CNS inflammation associated with seminoma.

Two cases in which a neurological disorder was identified pathologically to be due to a granulomatous infiltration were found after diagnosis to have an associated testicular seminoma with pathologically proven lymphatic metastasis. We present the clinical and imaging features, and pathological appearances of the lymphatic tissue and the brain. We summarise the literature to date and discuss the pathogenesis of the disorder and its treatment.

A case of florid intracerebral reaction to haematoma mimicking a tumour.

We present a patient with a suspected intracerebral malignant lesion admitted with signs and symptoms of an intracerebral mass lesion and managed operatively. Histological diagnosis demonstrated papillary endothelial hyperplasia (Masson's tumour). This highlights the ability of benign reactive processes associated with intracerebral haematoma to clinically and radiologically mimic neoplastic lesions.

The interpretation of phrases used to describe uncertainty in pathology reports.

Histopathological reports frequently contain phrases describing the degree of uncertainty of the diagnosis. We examined the interpretations of such terms by cellular pathologists, other doctors, and medical students. 203 respondents estimated the degree of certainty they would associate with the following phrases in a cellular pathology report: the features are indicative of; raise the possibility of; are compatible with; are probably those of; are diagnostic of; are in keeping with; and are suggestive of. For all phrases assessed other than "diagnostic of", all groups showed a wide spread in the interpreted probability. For example, the probability associated with the term "in keeping with" by individual consultant pathologists ranged from 25 to 100%. This study demonstrates that pathologists vary widely in how they interpret the meaning of phrases describing probability that are commonly used in pathology reports. We suggest that this potential risk is highlighted during pathology training.

Screen for IDH1, IDH2, IDH3, D2HGDH and L2HGDH mutations in glioblastoma.

Isocitrate dehydrogenases (IDHs) catalyse oxidative decarboxylation of isocitrate to α-ketoglutarate (α-KG). IDH1 functions in the cytosol and peroxisomes, whereas IDH2 and IDH3 are both localized in the mitochondria. Heterozygous somatic mutations in IDH1 occur at codon 132 in 70% of grade II-III gliomas and secondary glioblastomas (GBMs), and in 5% of primary GBMs. Mutations in IDH2 at codon 172 are present in grade II-III gliomas at a low frequency. IDH1 and IDH2 mutations cause both loss of normal enzyme function and gain-of-function, causing reduction of α-KG to D-2-hydroxyglutarate (D-2HG) which accumulates. Excess hydroxyglutarate (2HG) can also be caused by germline mutations in D- and L-2-hydroxyglutarate dehydrogenases (D2HGDH and L2HGDH). If loss of IDH function is critical for tumourigenesis, we might expect some tumours to acquire somatic IDH3 mutations. Alternatively, if 2HG accumulation is critical, some tumours might acquire somatic D2HGDH or L2HGDH mutations. We therefore screened 47 glioblastoma samples looking for changes in these genes. Although IDH1 R132H was identified in 12% of samples, no mutations were identified in any of the other genes. This suggests that mutations in IDH3, D2HGDH and L2HGDH do not occur at an appreciable frequency in GBM. One explanation is simply that mono-allelic IDH1 and IDH2 mutations occur more frequently by chance than the bi-allelic mutations expected at IDH3, D2HGDH and L2HGDH. Alternatively, both loss of IDH function and 2HG accumulation might be required for tumourigenesis, and only IDH1 and IDH2 mutations have these dual effects.

Base-rate error in the interpretation of immunohistochemistry.

Failure to appreciate the importance of the frequency of a disorder in the appropriate population (the base rate) may lead to the misinterpretation of the diagnostic significance of unexpected test results (unexpected test result defined in this context as a test result that is positive in a higher proportion of cases of an alternative diagnosis than in the diagnosis considered most likely before the test). This study aimed to determine whether pathologists are vulnerable to this error. Pathologists were asked to estimate the probability of tumour B in a scenario in which, prior to the immunostaining result, an experienced pathologist considers there to be a 99% chance that the patient has tumour A and a 1% chance that they have tumour B. Antibody X is positive in 80% of cases of tumour B and negative in 90% of cases of tumour A and is positive in the case described in the scenario. The estimates made by consultant pathologists ranged from 0 to 100% (mean 29.7%). The Bayesian answer would be 7.5%. These findings suggest that base-rate error may lead some pathologists to overestimate the implications for the likelihood of a diagnosis in the light of an unexpected immunohistochemical result.

Liposarcomatous differentiation in malignant peripheral nerve sheath tumor: a case report.

A 63-year-old man was admitted at the emergency department in an acute confusional state, and a computerized tomography scan (CT) revealed hydrocephalus. Despite the rapid introduction of a ventriculo-peritoneal shunt, the patient died soon thereafter. At the post-mortem examination, a large solid mass was found to be firmly attached to a nerve root at the L1-L2 level. Microscopically, the tumor showed the classical features of a malignant peripheral nerve sheath tumor (MPNST) with rhabdomyoblastic differentiation. In addition, there were randomly distributed lobules of well-differentiated adipose tissue with unequivocal atypical nuclei. The diagnosis of MPNST with rhabdomyoblastic and lipoblastic differentiation was made. We are not aware of previously reported lipoblastic differentiation in MPNST. Herein, we present details of the case.

Schwannoma with monoclonal plasma cell infiltration.

The authors report a very rare case of a vestibular schwannoma with an infiltrate of monoclonal plasma cells. A 45-year-old woman underwent routine excision of a presumed vestibular schwannoma. Histological analysis revealed the presence of a distinct lambda light chain restricted plasma cell population within the schwannoma. The light chain restriction and polymerase chain reaction-demonstrated monoclonality of the plasma cell population suggested the co-occurrence of a plasma cell neoplasm within a schwannoma. A search for systemic disease of plasma cell origin was unremarkable. A search of the literature suggests that this is the first report of such an occurrence.

Metastatic atypical choroid plexus papilloma: a case report.

Choroid plexus papillomas (CPPs) are rare adult tumours and metastatic disease is even less common, more typically associated with choroid plexus carcinoma. We present the case of a 32-year-old patient with multiple metastases arising along the length of the neuraxis 3 years after resection of an atypical fourth ventricular CPP. Metastatic deposits were found from the mid-brain to the lumbar cistern and the patient underwent repeat excision of the fourth ventricular tumour, partial resection of a cervico-thoracic deposit and craniospinal radiotherapy. Possible explanations for the rarity of atypical CPP include unclear diagnostic criteria leading to under-representation in reported cases. We review the current literature on metastatic CPP and discuss the role of surgery and adjuvant therapy in relation to both typical and atypical disease.

PPAR-gamma expression in pituitary tumours and the functional activity of the glitazones: evidence that any anti-proliferative effect of the glitazones is independent of the PPAR-gamma receptor.

OBJECTIVE: It has been reported that both normal pituitary and pituitary tumours express PPAR-gamma, a nuclear hormone receptor, the expression being more abundant in pituitary tumours, and that this is the basis for the reported antiproliferative effects of the thiazolidinedione, rosiglitazone, in animal models. However, the mechanisms for the responsivity to rosiglitazone have remained unclear. DESIGN AND MEASUREMENTS: To investigate this further, 'real-time' PCR was used to assess PPAR-gamma mRNA expression, and Western blotting and immunohistochemistry to study its protein expression, in 46 human pituitary tumours and normal pituitary tissue. Cell proliferation of the GH3 pituitary cell line was assessed by [3H]-thymidine-incorporation after 48 h rosiglitazone and pioglitazone (10(-4) M- 10(-10) M) treatment alone, or rosiglitazone in combination with the PPAR-gamma antagonist GW9662. RESULTS: PPAR-gamma mRNA and protein was found to be expressed in normal pituitary and was variably expressed in pituitary tumours, but were increased specifically in nonfunctioning pituitary adenomas. However, very little staining was observed with immunohistochemistry, with only occasional cell nuclei stained, and no difference was detectable between controls and tumours. Rosiglitazone at 10(-4) M and 10(-5) M concentrations inhibited cell proliferation (10(-4) M 14.0% +/- 1.5% and 10(-5) M 67% +/- 4%[mean +/- SEM]vs Control 100% +/- 3%, P < 0.0001) while lower concentrations showed no significant effect. Following withdrawal of rosiglitazone 10(-5) M, the cells fully recovered at a further 48 h, while lower doses showed a 'rebound' of stimulation. Pioglitazone was of similar potency to rosiglitazone in inhibiting proliferation. The PPAR-gamma antagonist did not show a significant reversal of the antiproliferative effect of rosiglitazone, and indeed suppressed proliferation on its own. CONCLUSIONS: Our data suggest that the antiproliferative action of rosiglitazone is probably not via PPAR-gamma.

A highly vascular intracranial solitary fibrous tumor treated with radiotherapy and toremifene: case report.

OBJECTIVE AND IMPORTANCE: A case of an unusual intracranial solitary fibrous tumor with features of high vascularity and resultant difficulty at resection is presented. The use of surgery, radiotherapy, and toremifene has been successful with no recurrence after 18 months. CLINICAL PRESENTATION: A 33-year-old male patient presented with a 1-year history of loss of vision on the left side and a 3-month history of headache and lethargy. Magnetic resonance imaging showed a lobulated mass (7.6 x 4.5 cm) in the left temporal fossa and left parasellar, sellar, and suprasellar regions, with a "dural tail" more typical of meningioma. Vascular supply was from both the internal carotid arteries and the left middle meningeal artery, precluding embolization. INTERVENTION: At the time of the craniotomy, a highly vascular tumor was found. Intraoperative hemorrhage limited resection to 20% of the tumor. The histological diagnosis was of a solitary fibrous tumor with an unusually angiomatoid architecture. After the operation, radiotherapy and toremifene were administered. A dramatic reduction in the size of the tumor was seen with no recurrence to date. CONCLUSION: The use of surgery, radiotherapy, and toremifene in treatment of a vascular intracranial solitary fibrous tumor has been successful and warrants further research.

Cervical spine chordoid meningioma. Case report.

Chordoid meningiomas are a rare but increasingly recognized subtype of meningioma. Although some cases have been associated with systemic symptoms, in many instances the clinical features are indistinguishable from those associated with other subtypes of meningioma. Given the prognostic significance of the diagnosis of chordoid meningioma, careful consideration should be given to the diagnosis during histological assessment. The authors describe a rare case of chordoid meningioma in the cervical spinal region.

Observations on the human rejection behaviour syndrome: Denny-Brown revisited.

The parietal avoiding-rejection behaviour syndrome, first described by Denny-Brown in the rhesus monkey, has been reported only rarely in humans. Here, we describe a patient with rejection behaviour in the setting of progressive cognitive decline accompanied by cortical myoclonus.

Metastatic choroid plexus papilloma: a case report.

Choroid plexus papillomas (CPPs) are generally regarded as benign tumours, with a favourable long-term prognosis. Complete resection should result in cure. We present a case of diffuse craniospinal seeding from an apparently completely resected fourth ventricular primary tumour. A 51-year-old male is discussed, who presented 5 years following complete resection of a CPP from the fourth ventricle, with a progressive history of left sided tinnitus, hearing loss, impotence and recent low back pain. Imaging demonstrated multiple craniospinal lesions explaining his symptomatology. Differential diagnosis lay between long standing CSF seeding, malignant transformation in the primary tumour, or metastatic spread from an undefined source. He underwent whole body FDG-PET scan which demonstrated a single metabolically active lesion in the sacral canal. A subtotal excision biopsy of this sacral lesion was performed which was indistinguishable histologically from the primary tumour resected from the fourth ventricle. Histological and functional imaging characteristics of the primary tumour have been unhelpful in predicting its subsequent behaviour. The present case illustrates the extremely rare consequences of metastases from this histologically benign tumour and adds to the literature on metastatic craniospinal disease.

Osteosarcoma and fibrosarcoma caused by postoperative radiotherapy for a pituitary adenoma. Case report.

Sarcomatous change is a rare complication of postoperative radiotherapy for pituitary adenomas. The authors report on what they believe to be the first case in which fibrosarcoma and, later, osteosarcoma developed during a 14-year period following surgery and radiotherapy for a nonsecreting pituitary macroadenoma.

Primary low-grade B-cell lymphoma of mucosa-associated lymphoid tissue of the dura mimicking the presentation of an acute subdural hematoma. Case report and review of the literature.

The authors present the case of a 64-year-old woman who experienced a left hemiparesis. An initial diagnosis of subdural hematoma was made based on results of computerized tomography scanning. Subsequent magnetic resonance imaging indicated an extraaxial meningioma. Histological findings confirmed an extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT). The authors outline the natural history of central nervous system lymphomas and of MALT lymphomas in other tissues. They review seven previously reported cases and emphasize the importance of recognizing these tumors as a distinct clinicopathological entity.