Pathology (Pathology )

Publisher: Royal College of Pathologists of Australasia, Taylor & Francis


Pathology is committed to publishing peer-reviewed, original articles related to the science of pathology in its broadest sense, including chemical pathology, experimental pathology, genetics, haematology, histopathology, immunology, microbiology, molecuar pathology and morbid anatomy. Call for Papers Manuscripts to be considered for publication should be submitted to the Editor: Professor C. S. Lee, Editorial Office, Royal College of Pathologists of Australasia, Durham Hall, 207 Albion Street, Surry Hills, NSW 2010, Australia. Tel: +61 2 8356 5858; Fax: +61 2 8356 5828. All submissions will be independently judged by at least two referees. Authors should consult the ' Notes for Contributors ' before sending a manuscript.

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Publications in this journal

  • [Show abstract] [Hide abstract]
    ABSTRACT: Pleomorphic xanthoastrocytoma (PXA) is an uncommon low grade astrocytic tumor and molecular alterations commonly observed in other WHO grade II gliomas, such as TP53 mutation, EGFR amplification, 1p19q deletion, are rarely seen. A 25-year-old woman experienced generalized seizures; a left temporal lesion in was identified in 2001. Resections were performed in 2004 and 2011 with a diagnosis of PXA, WHO grade II. The patient was treated with radiation and chemotherapy, but recurrence was found in 2013. The pathology of the craniotomy resection showed tumor necrosis and increased proliferation index (25% by Ki-67), and the diagnosis of PXA with anaplastic features exhibiting leptomeningeal infiltration was rendered, which likely represented malignant transformation. Targeted next-generation sequencing analysis was performed at Genomic Pathology Service (Washington University). A potentially actionable BRAF gene mutation (p.V600E) as well as potentially relevant TP53 gene p.R158H mutation was identified. The patient is on Vemurafenib and the lesion is stable on MRI. PXA has been shown to have BRAF mutations in 60-70% of cases. PXA with anaplastic features is a rare entity and has significantly worse prognosis. Vemurafenib is suggested to cross the blood-brain barrier and the patients with BRAF mutated brain tumors would benefit from BRAF targeted therapies.
    Pathology 10/2014; 46 Suppl 2:S28-S29.
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    ABSTRACT: Diagnosis and management of lung cancer, the world's most common cancer, has been transformed over the past decade. This transformation has emerged from the molecular analysis of these cancers and the demonstration of the critical role of molecular diagnosis in understanding lung cancer biology, therapy response, and outcome. The demonstration of the critical treatable mutations in the EGFR gene in a subset of lung adenocarcinomas in 2004 and, subsequently, rearrangements of ALK in 2007, has led to professional guidelines from three organizations-College of American Pathologists (CAP), Association for Molecular Pathology (AMP), and International Association for the Study of Lung Cancer (IASLC)-for standardization of clinical practice around the world to implement these analyses into routine patient care. Even as EGFR and ALK analysis are becoming routine, newer markers with similar potential are being discovered and implemented into clinical trials. This presentation will address the historical development of EGFR and ALK analysis in lung cancer, as well as newer, emerging targets (such as ROS1, RET, and MET), as we evolve from a purely histologic classification of lung cancer towards a classification strategy that incorporates molecular pathology.
    Pathology 10/2014; 46 Suppl 2:S1.
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    ABSTRACT: Small round cell lesions in the neck of a pediatric patient may involve a lymph node or present as an extra-nodal solid tumor. Various proliferative lymph node lesions include non-specific reactive hyperplasia, infectious mononucleosis, Castleman's disease, Rosai-Dorfman disease, Langerhans cell histiocytosis and malignant lymphoma. Besides lymphomas, the other pediatric small round cell tumors (SRCT) of the neck can be a group of malignancies that include neuroblastoma, Ewing's sarcoma, embryonal rhabdomyosarcoma, and metastasis from retinoblastoma and small cell undifferentiated carcinoma. These lesions are characterized both histologically and cytologically by predominantly small round to oval cells. Special morphological features characterizing these lesions are exclusive noncohesive cells and lymphoglandular bodies for non-Hodgkin lymphoma; rosette formation and filamentous background for neuroblastoma; nuclear molding, acinar formation and paranuclear blue inclusion for metastatic small cell undifferentiated carcinoma; glycogen vacuoles for Ewing's sarcoma; and tadpole cells for embryonal rhabdomyosarcoma. However, the so called characteristic cytomorphologic features may not be obvious or may be observed in more than one SRCT. To solve the differential diagnostic problems, ancillary studies like cytochemistry, immunocytochemistry, ultrastructure, flow cytometry, cytogenetics and molecular techniques may be of help. The present case is that of a small round cell lesion of neck in an 11-year-old girl.
    Pathology 10/2014; 46 Suppl 2:S9.
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    ABSTRACT: I will be demonstrating a case of diffuse leptomeningeal neuroepithelial tumor of childhood, which is a little recognized oligodendroglia-like tumor typically affecting diffusely the leptomeninges of children. This is the original case reported in the paper by Ng and Poon. It is recently re-described by a few groups and likely to be recognized as a distinct entity in the future.
    Pathology 10/2014; 46 Suppl 2:S29.
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    ABSTRACT: Xanthomatous infiltrate indicates aggregation of foamy histiocytes in the dermis. It may show nodular, interstitial, diffuse, perivascular, perifollicular pattern and corresponds to various disorders, including neoplasm, deposition, inflammation, and infection. Usually xanthomatous infiltrate represents hyperlipidemic xanthoma, such as eruptive xanthoma, tuberous xanthoma, and xanthelasma. They can be also seen in normolipidemic conditions, including diffuse plane xanthoma, papular xanthoma, and verruciform xanthoma. Xanthomatous infiltrate can also be seen in certain infectious diseases, especially lepromatous leprosy. This lecture reviews and summarizes various conditions of cutaneous xanthomatous infiltrate and emphasizes the diagnostic pitfalls in different settings.
    Pathology 10/2014; 46 Suppl 2:S10.
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    ABSTRACT: Since the publishing of The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) in 2008, many countries have adopted the system and the results have been reported. In Korea, TBSRTC has been used officially since 2010 and the results are being reported. In this short course, I plan to discuss the systems pros and cons based on our experience.The pros are that the system issues recommendation for treatment or follow-up and malignant ratio for each category, and that the system uses uniform terminology which offers easy and accurate communication and enhances reliable sharing of data. The cons are that because the issued malignant ratio is not a real data and it is actually different in every institution, the offered recommendation needs to be accommodated.
    Pathology 10/2014; 46 Suppl 2:S13.
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    ABSTRACT: The 2008 WHO classification of tumors of hematopoietic and lymphoid tissues has adopted consensus guidelines for the definition of well-defined entities. The major principle of the classification is the recognition of distinct diseases according to a combination of morphology, immunophenotype, genetic, molecular and clinical features. These disease entities are stratified according to their cell lineage and their derivation from precursor or mature lymphoid cells. Although the new 2008 WHO classification intentionally does not divide lymphomas by grade, traditionally mature B-cell lymphomas composed mainly of small lymphocytes have been called low-grade lymphomas. These small B-cell lymphomas include chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL), follicular lymphoma (FL), nodal marginal zone lymphoma (MZL), MALT lymphoma, hairy cell leukemia, and lymphoplasmacytic lymphoma (LPL). An entity that should be included in the differential diagnosis of lymphomas composed mainly by small lymphocytes but with a rather aggressive behaviour is mantle cell lymphoma (MCL).As a consequence of new and better available techniques in routine diagnosis, an increased recognition of early and precursor lesions of lymphoid neoplasms has emerged. This talk aims to review the morphological and phenotypic characteristics of the most frequent small B-cell lymphomas and expand on emerging concepts like, BCL2 negative FL, grading of FL, Pediatric FL, and indolent and cyclin D1 negative MCL, differential diagnosis of CD5+ low-grade lymphomas and more.
    Pathology 10/2014; 46 Suppl 2:S21.
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    ABSTRACT: Fibroblastic and myofibroblastic tumors represent a relatively common group of soft tissue lesions that includes reactive, hamartomatous and neoplastic conditions. The neoplastic tumors range from benign to intermediate to fully malignant neoplasms, capable of metastasis leading to the death of patient. These tumors can be diagnostically challenging because of the morphologic and immunohistochemical overlap, despite the clinical and molecular differences. As a general rule, superficial soft tissue tumors, especially cutaneous tumors, are less aggressive than deep tumors. In this short overview, several fibroblastic and myofibroblastic tumor entities which can involve the skin will be discussed with emphasis on the clinicopathological features, differential diagnosis, and the rule of immunohistochemical and molecular studies in their diagnosis. Recent advances/developments in this subject will also be reviewed.
    Pathology 10/2014; 46 Suppl 2:S11.
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    ABSTRACT: An 8.5-year-old girl presented with breast development, irregular uterine bleeding, and a spurt in height during the previous 9 months. She also complained of rapid increase of abdominal girth and body weight (4 kg). No remarkable past history or family history was noted. Her height (143 cm), breast development (Tanner stage 3), and pubic hair (Tanner stage 2) were compatible with precocious puberty. Laboratory examinations showed microcytic hypochromic anemia (Hb 9.2 g/dL), and serum estradiol was 138 pg/mL. LH and FSH were in the undetectable level even after a LH-RH (100 μg) injection. Ovarian tumor markers including CEA, CA19-9, CA125, α-fetoprotein, and hCG were within the normal range. Magnetic resonance imaging revealed a giant multilocular cystic tumor (25 × 14 × 10 cm) in the lower abdomen.Tumor resection was performed. The tumor originated from the right ovary and contained 3500 × mL of yellowish serous fluid. The left ovary was grossly normal. The resected right ovarian tumor was multilocular cystic, measuring 16.0 × cm in the greatest dimension, with occasional foci of whitish yellow elevated components in the cystic wall.
    Pathology 10/2014; 46 Suppl 2:S17.
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    ABSTRACT: An expert panel has recommended sessile serrated adenoma/polyp (SSA/P) be diagnosed if one crypt in a serrated polyp shows unequivocal architectural distortion, dilation and/or horizontal branching. In our practice, SSA/Ps represent 12.1% (WHO criteria) or 14.7% (expert panel criteria) of all polyps received, the highest levels yet reported. The expert panel defined SSA/Ps with cytological dysplasia (SSAD) as an advanced polyp with abrupt transition from typical SSA/P morphology to an area of cytological dysplasia. In our study, SSADs were no larger than SSA/Ps, represented 3.5% of SSA/Ps and 11% occurred in the left colon. Progression to SSAD involves not only MLH1 loss and microsatellite instability but p53 mutation and wnt pathway activation. In a study of 200 traditional serrated adenomas (TSAs), we demonstrated flat as well as protuberant growth, slit-like serrations as an important diagnostic feature and different clinicopathological associations of morphologically identical BRAF- and KRAS-mutated TSAs. Advanced TSAs showed abrupt transition to overt dysplasia with p53 mutation, wnt pathway activation and in BRAF-mutated polyps, loss of p16. Morphologically similar serrated tubulovillous adenomas show some TSA-like features but not slit-like serrations. They demonstrate KRAS mutation, negligible CIMP and are the likely precursors of most microsatellite stable serrated adenocarcinomas.
    Pathology 10/2014; 46 Suppl 2:S17.
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    ABSTRACT: Histopathological diagnosis of interstitial pneumonia (IP) requires experiences and is often challenging for general surgical pathologists. In its context, accurate recognition of histopathological usual interstitial pneumonia (UIP) and nonspecific interstitial pneumonia (NSIP) patterns along with separation of idiopathic IPs from ones associated with hypersensitivity pneumonia and systemic connective tissue disease are the critical points. Several reports had indicated insufficient interobserver agreement of IP diagnosis, and we also have investigated the interobserver agreement of chronic interstitial pneumonia in various conditions showing that reproducibility of pathological judgment of above points was not greatest. To improve the reproducibility of diagnosis, recent publication of IPF guidelines set criteria of pathological UIP. It indeed helps pathologists to evaluate definite UIP pattern and works well for pulmonary pathologists, however, it still have some confusions and difficulties to the general surgical pathologists. In the course, summary of interobserver agreement along with our own data among pulmonary and general pathologists before and after the new guidelines will be shown. I will also share possible causes of confusion with audience and suggest a few tips for the improved histological assessment.
    Pathology 10/2014; 46 Suppl 2:S37-S38.
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    ABSTRACT: The subcutaneous fat is a metabolic depot and also provides insulation from trauma. The subcutis is divided into lobules by fibrous septa. Within the fibrous septae course the small arteries, arterioles, veins and small nerve fibres. The nutrient artery supplies the centre of the lobule and drains to venules within the septum. Inflammatory disorders of the subcutaneous fat can be grouped into three main categories: 1) Septal panniculitis. 2) Lobular panniculitis. 3) Panniculitis associated with large vessel vasculitis.Most panniculitis are strictly speaking mixed but the classification is based on the predominant area of involvement.In septal panniculitis the inflammation is centred upon the connective tissue septa. There is often some spill over of the inflammatory cells into the periphery of the lobule. Erythema nodosum (EN) is the prototype of septal panniculitis. Other disorders associated with a septal panniculitis include necrobiosis lipoidica, factitial panniculitis, nephrogenic systemic fibrosis, cellulitis and microscopic polyangiitis.In the lobular panniculitides the inflammation is centered mainly within the lobule. Examples of lobular panniculitis include nodular vasculitis, lupus panniculitis, subcutaneous fat necrosis of the newborn, sclerema neonatorum, cold panniculitis, a1 anti-trypsin deficiency and pancreatic panniculitis.
    Pathology 10/2014; 46 Suppl 2:S10.
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    ABSTRACT: Cambodia is one of underserved countries in Southeast Asia and is still suffering from its terrible history in the last 30 years when no pathologist survived from the genocide of Khmer Rouge regime. Today only 8 pathologists, mostly under qualified, are on service for more than 14 million inhabitants. There are 8 laboratories diagnosing 25,000 to 27,000 histological specimens and non-gynecological cytology, and 24,000 to 25,000 Pap smear screening per year. All laboratories are commonly providing routine histology with most on HE, Giemsa, PAP, and PAS staining. Two laboratories have a capability to provide some immunohistochemistry staining, mostly for only some markers to differentiate lymphomas and carcinomas. At present, no frozen section and no autopsy can be done in Cambodia. All these 8 laboratories are concentrated in the capital city and there is no pathology laboratory in provinces. Four laboratories have established a telepathology or personally have connection to outside world via E-mail. We have two intentions to send the cases to experts: one is to confirm our own diagnosis, second is to discuss the difficult and complex cases with senior experts to get a hint of reliable diagnosis. One lab has built up a clinico-pathological teleconference (CPC) in order to get a good connection and discussion for difficult cases. However, we still have challenging to the limits of teleconsultation due to the available experts time even the optimal clinical information, macro-images, X-rays, CT-scans, MRI are together submitted with microscopic images. There is a gap between newly established therapeutic facility, (e.g., hormone therapy in breast cancer, chemotherapy in soft tissue tumor) and the poor histological and immunohistochemistry methods in the country. Another problem is a personal isolation of Cambodian pathologists with low economic situation who cannot frequently attend international meeting outside of the country. Therefore the training level of Cambodian pathologists cannot be adapted to the standard which is demanded worldwide for sufficient tumor therapy.
    Pathology 10/2014; 46 Suppl 2:S8.
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    ABSTRACT: Although 20 century reforms in medical education and healthcare have led to an impressive doubling of human life-span, there remain many gaps and inequalities in the 21 century, as reflected by the larger disease burden in low income countries, brain drain of workforce to richer countries, the 10/90 gap in research investments, and inequalities in expenditure for laboratory diagnostic services. Compounding these are the demands of more complex health care systems, evolving roles of pathologists, and a rapidly changing environment. Climate change, urbanization and rapid global travel have led to disease emergence which impact on the pathology services. The challenges in under-resourced countries are particularly acute. International pathology organizations, while tending to focus on advances in pathology practices, should do more to address inequalities of health and challenges faced by countries-in-need. Global networks should discuss key global challenges, enhance global cooperation in capacity-building as well as advocate for strategic pathology developments in tandem with other medical disciplines, particularly where the need is greatest. Pathologists play prominent roles in academia, and can be agents of change both as individuals and through academic consortia to bring about reforms in pathology education and training, and in research-capacity strengthening of less developed countries.(Figure is included in full-text article.).
    Pathology 10/2014; 46 Suppl 2:S2-S4.
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    ABSTRACT: NGS is a new approach used to identify genetic mutations that may underline kidney disease. The advantages of NGS compared to Sanger sequencing are the ability to run multiple samples simultaneously, shorter turn-around time and lower cost. For example, compared to older methods that took weeks to complete, NGS can shorten the turn-around time for Alport syndrome diagnosis to just 6 days and the cost to 40%. In addition custom NGS can be designed to identify mutations in a selected group of genes associated with proteinuria and FSGS on renal biopsy. FSGS can be a histologic manifestation of a variety of glomerular diseases including specific podocyte gene mutations (NPHS2, PLC1E, CD2AP, TRPC6) but also glomerular basement membrane abnormalities due to COL4A3-5 mutations. Using custom designed NGS on 14 patients and 19 selected genes, we have identified novel and rare mutations in COLA3, COLA4 AND COLA5, but also mutations in LAMA5 in patients phenotyped as FSGS. Other patients with FSGS were found to have a 6p deletion in APOL1 that is known to be associated with the development of FSGS in African Americans. In this cohort, some patients had congenital hydronephrosis and VUR induced proteinuria. There was no history of familial disease. One of these patients unexpectedly was found to have a novel COLA3 mutation in addition to an expected SALL2 mutation known to be associated with urinary tract developmental anomalies. NGS results were verified using Sanger sequencing. The findings in this study suggest that NGS is a powerful method to identify specific structural changes in the genome that could not have been predicted by the histopathological phenotype. A high throughput approach for mutation analysis is more advantageous compared to single gene approaches and promises to become a clinically useful diagnostic tool.
    Pathology 10/2014; 46 Suppl 2:S39-S40.
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    ABSTRACT: The purpose of this course will be to provide pathologists with an update on breast core needle biopsy procedures using examples of such cases to address areas of recurrent diagnostic difficulty. The educational needs we will be targeting are primarily medical knowledge. We will select cases that constitute recurrent diagnostic problems and discuss challenges presented by such lesions and the entities that may mimic them. We will draw on our experience of core needle biopsy specimens seen in our practices to select cases as well as utilize peer-reviewed publications to support our discussions. The major educational objectives are to ensure competence in diagnosing breast lesions on core needle biopsy specimens; to understand the clinical significance of a variety of breast lesions with particular reference to the implications of these diagnoses in core needle biopsy specimens and to understand the ramifications of these diagnoses with regard to patient management. Additionally, participants will learn to develop differential diagnoses of commonly encountered problems and to appreciate the uses and limitations of immunohistochemistry in solving diagnostic problems in breast core needle biopsy specimens. The importance of radiologic/pathologic correlation in every case will be addressed.
    Pathology 10/2014; 46 Suppl 2:S6.
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    ABSTRACT: Mucormycosis is a rare and often fatal infection caused by fungi of the Mucorales order, commonly affecting immunocompromised patients and adults with diabetic ketoacidosis. Infants are infected through the gastrointestinal tract or the nasopharynx, from where infection can spread to the brain. Mucor fungus is angiotropic, causing thrombosis, infarction and tissue necrosis.A case of neonatal death by mucor encephalitis is reported. The mother had gestational diabetes on insulin. The female infant was diagnosed with Fallot tetralogy and was admitted to NICU. There was a progressive clinical deterioration with signs of infection, but with repeatedly negative full septic screens including fungi, and negative viral control. The brain showed lytic lesions on imaging. Despite treatment with antibiotics and later with anti-fungal drugs, the baby's condition rapidly worsened and she died on day 34.The post-mortem examination revealed mucor hyphae in the brain causing vasculitis and necrotising encephalitis. In addition to tFallot, there was thymus hypoplasia, suggestive of DiGeorge phenotype. CATCH22 cytogenetic examination was negative.Diagnosis of infection with mucor and related fungi is difficult, as cultures are frequently negative. Direct microscopic visualisation of the fungal hyphae in affected tissues is important for the diagnosis, which is often made with delay or only post-mortem.
    Pathology 10/2014; 46 Suppl 2:S29-S30.
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    ABSTRACT: Primary mesenchymal tumors represent a rare subset of hepatic lesions with overlapping spindle cell morphology. These lesions pose unique diagnostic challenges for pathologists as they are infrequently seen in general practice and can be easily mistaken for their benign counterparts or mimickers. In the current era of personalized medicine, precise pathologic diagnosis of these lesions is critically important to guide targeted therapy. This expectation is difficult to meet when pathologists face uncommon lesions outside their scope of experience. This challenge is further exacerbated when interpreting small biopsy samples.In this lecture, we first present the clinicopathological features of 6 typical cases: inflammatory pseudotumor, angiomyolipoma, epitheleioid hemagioendothelioma, malignant fibrous histiocytoma, leiomyosarcoma, and follicular dendritic cell sarcoma. On each case, the focus of discussion is on the morphology characteristics and how to differentiate them from metastatic tumors, non-neoplastic lesions and other types of primary spindle cell neoplasms. We then outline a practical diagnostic approach based on the unique features of each entity. This lecture provides a comprehensive guidance to general pathologists and pathology trainees on how to navigate through this group of seemingly complex entities and to arrive at a specific diagnosis.
    Pathology 10/2014; 46 Suppl 2:S23.
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    ABSTRACT: Giant cell fibroblastoma is a rare fibroblastic tumor occurring mainly in young patients. Back of thigh, inguinal region and chest wall are the most common sites of involvement. The tumor is characterized by a locally aggressive behavior with no reported metastatic potential. Microscopically, it is composed of spindle cells with a moderate degree of nuclear pleomorphism that infiltrate deep dermis and subcutis. A distinctive feature of this tumor is the presence of peculiar pseudovascular spaces lined by a discontinuous row of multinucleated cells. Features very similar to dermatofibrosarcoma protuberans can be seen. Immunohistochemically, it shows positive staining for CD34, while being negative for S-100 protein and vascular markers. The molecular changes are overlapping with dermatofibrosarcoma protuberans. A case of giant cell fibroblastoma will be presented illustrating the clinicopathological and molecular features of this tumor.
    Pathology 10/2014; 46 Suppl 2:S11.
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    ABSTRACT: A 53-year-old male complained of urination discomfort and pain for three weeks. Physical examination noted swelling of legs and enlarged prostate. Imaging studies revealed irregular mass involving the prostate and seminal vesicles with obscured structural features, enlarged peri-iliac artery and peri-aortal lymph nodes, and suspicious metastatic lesions in the 4th-5th lumbar vertebrae. Serum PSA was not elevated. Ten cores of ultrasound-directed needle biopsies of the prostate were collected and submitted to the pathology department. Routine H&E histology reveals medium sized tumor cells infiltrating fibromuscular stroma in sheets or nests.Some tumor cells were distorted with indistinct morphology and hyperchromatic nuclei. Occasional perineural invasion was observed.
    Pathology 10/2014; 46 Suppl 2:S43.