Hwei Yee Lee

An unusual case of glomerulonephritis in a patient with non-Hodgkin Mucosal Associated Lymphoid Tissue (MALT) B-cell lymphoma

BackgroundKidney involvement in non-Hodgkin lymphoma is well recognized and glomerulonephritis, when present, has been commonly reported to be associated with a membranoproliferative pattern.Case presentationWe report a case of a 58-year-old lady with a recurrence of non-Hodgkin MALT B-cell lymphoma, presenting with acute kidney injury, nephrotic range proteinuria and a cellular urinalysis. She underwent a renal biopsy that showed a severe diffuse proliferative and exudative lupus-like glomerulonephritis, which is likely paraneoplastic in nature. We discuss the differential diagnosis and possible pathogenesis of glomerular injury in lymphoma-related proliferative glomerulonephritis.ConclusionDifferentiating between true lupus nephritis and a paraneoplastic glomerulonephritis is important, as it would have significant implications on treatment and clinical course.

Anaplastic supratentorial cortical ependymoma presenting as a butterfly lesion.

Background: Anaplastic cortical ependymomas are rare lesions with few cases reported in the literature. Case Description: We present a unique case of an anaplastic cortical ependymoma in a 51-year-old female presenting as a butterfly lesion with involvement of both frontal lobes. The patient underwent gross total resection of her tumor with further adjuvant treatment. We present the findings in our case and review the literature surrounding supratentorial ependymomas and their treatment outcomes. Conclusion: Rarely, cortical ependymoma can present as a butterfly lesion and should be considered in the differential diagnosis of such lesions in adults.

Proximal type epithelioid sarcoma arising in the base of the skull: a diagnostic challenge

Epithelioid sarcoma (ES) has been described in many sites1 and classical and proximal variants of ES display characteristic loss of INI1 expression.2 We detail, for what is believed to be the first time, a primary ES of the base of skull for which, because of extensive local disease, specific origin from dura or bone3 could not be determined. A 55-year-old Malay man presented with a 3-month history of epistaxis and visual disturbances. MRI scan revealed a large intracranial extra-axial lobulated mass measuring 7.0×6.1×7.3 cm with extension into the anterior cranial fossa, left posterior choana and left ethmoid sinus, suggesting a meningioma. The patient underwent tumour resection during which part of the skull base and small part of the left frontal lobe were removed. Intra-operatively, the lesion was extra-axial and remote from the normal appearing pituitary gland and suprasellar region. Postoperatively, a thorough physical examination, oesophago-gastro-duodenoscope and CT scan of the thorax, abdomen and pelvis failed to detect a primary tumour elsewhere. A repeat MRI of the brain and spine 1 month post surgery …

Cytological features of the native pineal gland in intraoperative squash preparations

The pineal gland, also known as the conarium, is one of the six circumventricular organs of the central nervous system. It has a location in the midline within the anterior quadrigeminal cistern, and lies above the superior colliculi, at the posterior recesses of the third ventricle. The pineal gland has unique histology among central nervous system tissues. It consists of prominent lobules surrounded by connective tissue septa. The pineocytes within the lobules form sheets within a fibrillary background, punctuated by distinctive pineocytic rosettes with central fibrillary cores. A population of astrocytes forms a loose network among the pineocytes. The pineocytes demonstrate immunoperoxidase expression of synaptophysin and neurofilament protein, while the supporting astrocytes are positive for glial fibrillary acid protein and S100 protein. Ultrastructural analyses of pineocytes have revealed morphological evidence of neurosensory differentiation by the presence of vesicle-crowned rodlets, fibrous filaments and paired twisted filaments, and also of neuroendocrine differentiation with dense core granules. After puberty, mineralized concretions known as corpora arenacea (or brain sand) become present and accrue with age. This is accompanied by gliosis and cystic change which gradually replace the cellular pineocytic population. Since the discovery of melatonin more than half a century ago, great strides have been made in characterization of the structure and function of the pineal gland. However to date, the cytological features of the normal pineal gland, as seen in intraoperative squash preparations has not been well illustrated in the literature. Intraoperative smear cytology using the technique of squash preparations is very commonly practiced in surgical neuropathology. This method provides superior morphological preservation in the neurosurgical setting where biopsies are often limited in size and the tissue is particularly vulnerable to freezing artefact. Unfortunately, the smear cytology features of the pineal gland are not familiar to many surgical pathologists, perhaps due to the relative rarity of lesions involving the pineal area, and the small size of the gland, rendering it readily overrun and destroyed by aggressive neoplasms. As lesions of the pineal region are being increasingly targeted by stereotactic biopsies and submitted for intraoperative diagnosis, knowledge of the cytological features of the normal pineal gland as encountered in the intraoperative setting is of importance. An ability to distinguish normal pineal tissue from lesional tissue is pivotal in intraoperative management; the finding of normal tissue prompts further surgical sampling to identify the actual lesion under the same anesthetic procedure. In this report, we describe the features of the native pineal gland on intraoperative squash preparation, as fortuitously encountered in a biopsy of a pineal lesion in a young female. The intraoperative smears were moderately cellular with cohesive clumps of cells within a fibrillary background. Peripheral areas of cellular discohesion were seen (Fig. C-1). The cells (pineocytes) formed sheets and rosettes with Department of Pathology, Tan Tock Seng Hospital, 11 Jalan Tan Tock Seng, Singapore, Singapore Department of Neurosurgery, National Neuroscience Institute, 11 Jalan Tan Tock Seng, Singapore, Singapore *Correspondence to: Khoon Leong Chuah, M.B.B.S., F.R.C.P.A., Department of Pathology, Tan Tock Seng Hospital, 11 Jalan, Tan Tock Seng, Singapore 308433, Singapore. E-mail: gzzckl@singnet.com.sg Received 3 January 2010; Accepted 29 January 2010 DOI 10.1002/dc.21373 Published online 14 May 2010 in Wiley Online Library (wileyonlinelibrary.com).

An unusual cause of nodular skin lesions with ulcer

A 51-year-old Chinese man presented to a general practitioner with a left ankle ulcer of a few weeks duration. He had no significant medical history and denied smoking or alcohol intake. There was no history of previous trauma to the limb. He was referred to a hospital and after consultation with the vascular surgeons and dermatologists, a diagnosis of chronic eczema with factitious ulceration was made. He was treated empirically with steroid cream and antibiotics. However, the ulcer persisted and enlarged over a period of 3 months, being associated with a foul smelling whitish discharge. In addition, new skin nodules appeared over the back and limbs over a period of 3 weeks in association with fever and rigors. He sought treatment at our institution. On physical examination, there was a large confluent gangrenous ulcer over the left ankle. There was no impairment of sensory or motor functions of the affected limb. Multiple cutaneous and subcutaneous nodules and plaques with necrotic centres were present over the trunk and limbs. Otherwise, physical examination was essentially unremarkable, particularly no organomegaly or palpable lymphadenopathy was found. Blood investigations performed were unremarkable. Computed tomography (CT) scan of the thorax, abdomen and pelvis disclosed the presence of multiple enhancing cutaneous and subcutaneous nodules in the torso with minimal surrounding inflammatory change. No other abnormalities, particularly lymphadenopathy, were detected. Doppler ultrasound study indicated the absence of significant arterial disease or deep vein thrombosis of the lower limbs. An excision biopsy from a skin lesion over the upper back was subsequently performed. Following the histology report of the skin excision specimen, the patient underwent an examination by an otolaryngologist during which no lesion was detected in the nasal region. In addition, subsequent bone marrow trephine biopsy did not reveal any abnormal cellular infiltrate.

Synchronous multicentric glioblastoma with PNET and O subtypes: Possible pathogenesis

Background: Glioblastomas (GBM) are highly infiltrative, cellular and mitotically active tumors with large histologic variations within and between tumours. Several subtypes have been described including the GBM with oligodendroglial differentiation (GBM-O) and primitive neuroectodermal tumour components (GBM-PNET). We report the first described case of a patient with synchronous multi-centric GBM-O and GBM-PNET components. Case Description: A patient, who presented with a short history of progressive headache and difficulty with memory recall, was found on MRI imaging to have two intracranial lesions. These showed heterogeneous enhancement and were found in the left frontal and left temporal regions. The patient underwent gross total resection of these two lesions which were found to show GBM-O and GBM-PNET differentiations. Conclusion: Although tumour cell migration in the context of GBM is a well-recognized phenomenon, the traditional hypothesis is not able to satisfactorily explain this case of multicentric GBM whereby the two lesions demonstrate different cell origins. More current understanding of the migratory pathways from the subventricular zone provide an alternate and plausible pathway that fits our patients unusual diagnosis.

A 58 Year-Old Male with Hallucinations and Ataxia

A 58 year old Caucasian male presented with weight and appetite loss over 2 to 3 months. He was recently diagnosed with HIV infection. His initial CD4 count was < 20 cells/mm (7%) with a viral load of 352000 copies/ml. He was started on highly active antiretroviral therapy (HAART) and in the third month of therapy, he presented with increasing hallucinations and ataxia. Serologies for hepatitisA, hepatitis B, CMV, toxoplasma, syphilis, tuberculosis (TB) and Cryptococcus neoformans were negative. His CSF profile was negative for Cryptococcus neoformans, TB, HSV, CMV, toxoplasma, VZV and EBV were negative. In addition, his CD4 count rose to 202 cells/mm with a viral load of 425 copies/ml. MRI showed an area of heterogeneous contrast enhancement affecting the deep nuclei as well as white and grey matter tracts with extension into the deep white matter of the right frontal, temporal and parietal lobes. This area exhibited mild mass effect compressing on the left lateral and third ventricles with early midline shift to the left (Fig. 1a). In view of the radiological findings, a clinical diagnosis of lymphoma was considered and the patient underwent a brain biopsy to ascertain the nature of the brain lesion.

Rosette-forming glioneuronal tumour of the fourth ventricle arising in the cerebellar hemisphere: diagnostic challenges including cytological features in intra-operative squash preparations

Rosette-forming glioneuronal tumour (RGNT) is an entity newly codified in the 2007 WHO classification of tumours of the central nervous system. RGNTs are rare and typically arise in the mid-line in the region of the fourth ventricle. Origin at other sites such as cerebellar hemisphere, spinal cord and supratentorial sites has been described. The tumour consists of distinct neurocytic and astrocytic components, the former featuring distinctive neuro-cytic rosettes and perivascular pseudorosettes, and the latter resembling pilocytic astrocytoma. An atypical site of presentation and a predominance of either the neurocytic or astrocytic components at intra-operative consultation present diagnostic challenges. The distinctive appearance of the tumour in intra-operative squash preparations is a clue to the diagnosis in this setting. We describe the case of a RGNT which arose in the left cerebellar hemisphere. The intra-operative squash preparations showed the neurocytic rosettes and pseudorosettes within a loose fibrillary and mucinous background. The biphasic nature of the lesion was manifest in the frozen section, but more apparent in subsequent tissue sections. The differential diagnoses of RGNT with oligo-dendroglioma, pilocytic astrocytoma, central and extraventricular neurocytoma and dysembryoplastic neuroepithelial tumour are discussed.

Malignant pecoma of the bone following uterine leiomyosarcoma: a potential diagnostic dilemma

Perivascular epithelioid cell tumour (PEComa) is a term applied to a family of mesenchymal tumour composed of varying proportions of spindle and epithelioid cell components associated with HMB45 expression. PEComa rarely arises in the soft tissue, visceral organs, skin and bone. A primary bone PEComa is extremely rare, with less than 15 cases reported in the literature. In this report, we detail yet another instance of a primary bone PEComa with malignant histological features which affected the L4 vertebral bone in a 46-year-old Chinese lady. Significantly, she had a past medical history of uterine leiomyosarcoma. Histology of the bone biopsy disclosed a proliferation of epithelioid cells with clear to eosino-philic cells associated with an arborising vascular network resembling a clear renal cell carcinoma but associated with HMB45 expression. Review of the uterine tumour disclosed a neoplasm with a different morphology not associated with HMB45 expression. The differential diagnoses of a PEComa affecting the bone, criteria for predicting its biological behaviour and its relationship with uterine leiomyosarcoma are presented. Awareness of the histological appearance and immunohistochemistry characteristics of PEComa are pivotal in achieving the correct diagnosis.

40. Immune reconstitution inflammatory syndrome associated with JC virus infection: brain biopsy findings of a patient

Background and Method The immune reconstitution inflammatory syndrome (IRIS) in the setting of HIV infection is a recently recognised clinical phenomenon resulting from restored immunity to various infectious or non-infectious agents upon initiation of highly active antiretroviral therapy (HAART). IRIS may be multi-systemic and characteristically presents with paradoxical clinical deterioration of a pre-existing condition or the emergence of a new condition after the initiation of HAART. The diagnosis is challenging and reports documenting brain biopsy findings are rare. We present a case report of a 58-year-old male who was recently diagnosed with HIV infection and started on HAART. Results and Conclusion The patient presented with rapidly progressive functional decline within 3 months of therapy. Serial magnetic resonance imaging (MRI) scans showed progression from no significant acute abnormalities to oedema and enhancing lesions of the deep white and grey matter of the frontal and parietal lobes, as well as the right side of the midbrain. As a diagnosis of lymphoma was considered clinically, a right frontal lobe biopsy was performed. On histology, the brain sample showed dense T lymphocytic infiltrate, smaller numbers of B lymphocytes and a prominent population of plasma cells. Reactive gliosis, micro-glial nodules and occasional bizarre astrocytes were seen. JC polyomavirus was detected both in the cerebrospinal fluid and the biopsy tissue. As a dense lymphoplasmacytic infiltrate cannot be attributed to JC virus infection alone, the picture was consistent with IRIS associated with JC virus infection. The awareness of IRIS as a potential mimic of lymphoproliferative disorders on histology can prevent diagnostic pitfalls especially during intra-operative consults.