[Pancytopenia and hemolysis--diagnosis, differential diagnosis and therapy of pernicious anemia]

Pernicious anemia and Vitamin B12 deficiency have a wide range of symptoms and are a common finding in the elderly. A 73 year old female is admitted to the hospital because of dyspnea, fatigue and loss of appetite and weight. While previous medical history and physical examination are inconspicuous, laboratory findings show severe pancytopenia with macrocytosis, low reticulocyte count and marked signs of hemolysis. A very low serum level of vitamin B12 and chronic atrophic type A gastritis upon endoscopy with presence of parietal cell antibodies in the serum lead to the diagnosis of pernicious anemia. Complete restitution is achieved by parenteral vitamin B12 substitution. Nowadays, severe pernicious anemia is only rarely seen. The differential diagnosis of pancytopenia (with macrocytic anemia) combined with hemolysis and the essential hints to the diagnosis of pernicious anemia are discussed, and thereby practical aspects including therapy actualized.

Familial hypocalciuric hypercalcaemia as a differential diagnosis of hyperparathyroidism:studies in a large kindred and a review of surgical experience in the condition

We have studied 46 members of a large kindred with familial hypocalciuric hypercalcaemia (FHH) after a neck exploration failed to cure hypercalcaemia in an asymptomatic patient. Serum calcium, serum phosphate, plasma parathormone and vitamin D metabolites do not distinguish affected members from patients with hyperparathyroidism. Because of the continuing debate as to whether or not FHH is a variant of, or distinct from, hyperparathyroidism, we have carried out a review of surgical experience with subtotal parathyroidectomy in hyperparathyroidism secondary to parathyroid hyperplasia and in FHH. Whereas the procedure is successful in 90 per cent of the former cases only one case of FHH has been cured by it. This provides evidence for the two conditions being aetiologically distinct. Before patients with asymptomatic hypercalcaemia are referred for parathyroid surgery the calcium:creatinine clearance ratio should be measured using a 2 h urine sample collected after an overnight fast and a fasting blood sample. If this ratio is less than 0.01 then screening of first degree relations should be undertaken before any parathyroid surgery is performed. Unnecessary surgery can therefore be avoided.

Immunohistochemistry as a fundamental tool for the differential diagnosis of polymorphous low-grade adenocarcinoma

Polymorphous low-grade adenocarcinoma (PLGA) is a subtype of salivary gland carcinoma with a marked predilection for the minor salivary glands. The diagnosis of this lesion can be a challenge in incisional biopsies because of its similarity to other salivary neoplasms and the difficulty of analyzing its infiltrative nature and neurotropism. Diagnosis can be facilitated, however, by immunohistochemistry, a technique that has become a fundamental tool to the pathologist. The purpose of this study was analyze the immunohistochemical aspects of 4 cases that were examined in the São José dos Campos School of Dentistry. The patients included 4 women, ages 32 to 57 years (mean, 50 years), who reported an intraoral painless lesion, ranging in size from 1 to 3 cm (mean, 1.75 cm) with a variable evolution period. Histologically, the lesions showed similar aspects, characterized by polymorphous growth pattern, including solid, cribriform, trabecular, papillary, and single-file arrays. The tumors showed positivity to cytokeratins (Cks) 7 and 8 and vimentin, variable expression for Ck 14, and a negative reaction to Cks 13 and 19 and muscle-specific actin. PLGA is a tumor of the salivary gland that must be distinguished from other neoplasms for therapeutic and prognostic considerations, and the panel of antibodies employed in this study was effective for its diagnosis.

Case for Diagnosis

A 27 year-old-man, with no known personal or familial history of disease, mentioned a 10-year history of asymptomatic groups of telangiectasias, with a Blaschko lines distribution on the right lateral aspect of the neck and asymptomatic. He denied any episodes of disease or drug intake that could be associated with the disease. Blood work had no changes, namely of liver enzymes or infectious serologies. The clinical diagnosis of Idiopathic Acquired Unilateral Nevoid Telangiectasia was made, an uncommon, benign vascular malformation. The patient declined doing a cutaneous biopsy or treatment with a cosmetic intent.

Diagnostic microbiologique de la pneumonie [Microbiological diagnosis of pneumonia].

Les pneumonies causent une mortalité et une morbidité significatives. De manière simplifiée, deux types de pneumonie sont décrits : la pneumonie communautaire et la pneumonie nosocomiale avec le pneumocoque et l'Haemophilus influenzae comme causes principales pour la première, le Pseudomonas et diverses entérobactéries pour la deuxième. La réalité est cependant plus complexe puisque l'on distingue aussi la pneumonie d'aspiration par exemple. La culture est très importante dans le cas des pneumonies nosocomiales car elle permet de déterminer la sensibilité aux antibiotiques de l'agent infectieux et d'adapter le traitement. Pour les patients immunosupprimés, le diagnostic différentiel est plus large et la recherche par tests moléculaires de certains virus, de champignons filamenteux et du Pneumocystis peut se révéler informative. Pneumonia is an importance cause of mortality and morbidity in adults. Two types of pneumonia are defined: community-acquired and nosocomial pneumonia with their corresponding etiology such as pneumococci or Haemophilus influenzae and Pseudomonas or enterobacteriaceae, respectively. However, the reality is more complex with aspiration pneumonia, pneumonia in immunocompromised patient, and pneumonia in ventilated patients. Culture in the case of nosocomial pneumonia is especially important to obtain the antibiotic susceptibility of the infectious agent and to adjust therapy. Moreover for immunocompromised patients, the differential diagnosis is much wider looking for viruses, filamentous fungi and Pneumocystis can be very informative, using new molecular assays.

Diagnosis and management of oral leishmaniasis--case series and literature review

The worldwide prevalence of leishmaniasis is increasing because of ecologic changes and increased medical profession awareness. Furthermore, solitary cases have been recently reported in Western countries. The authors describe the epidemiology, mode of transmission, and diagnosis of leishmaniasis and present 4 oral cases treated with systemic, localized, or combined therapy. The authors suggest that clinicians should maintain a high index of suspicion for atypical, resistant, oral and perioral lesions in individuals with a history of traveling in certain geographic regions. After diagnosis, treatment should be determined jointly by experts from the fields of oral and maxillofacial surgery, oral medicine, and dermatology based on leishmaniasis species and clinical presentation.

Potentially malignant epithelial oral lesions: Discrepancies between clinical and histological diagnosis

OBJECTIVE: To evaluate the discrepancy index between the clinical and histological diagnosis and the prevalence of epithelial dysplasia and carcinoma in 45 patients with potentially malignant epithelial oral lesions (PMEL). PATIENTS AND METHODS: We submitted 45 patients with PMEL to clinical examination and obtained a biopsy from each. The results of histological diagnosis were compared to the clinical diagnosis. RESULTS: Clinical diagnosis showed that the most common PMEL was leukoplakia followed by lichen planus and by actinic cheilitis associated with leukoplakia. The most common site was the buccal mucosa. Histological diagnosis revealed that 46.7% of the PMEL were lichen planus. The discrepancy index between clinical and histological diagnosis was 24.4%. The higher discrepancy index occurred among leukoplakias. The prevalence of epithelial dysplasia and carcinoma was 17.8%. CONCLUSIONS: We conclude that all PMEL should be submitted to a microscopic analysis because the discrepancy between clinical and histological diagnosis was present in a quarter of these lesions. Otherwise, the epithelial dysplasia and carcinoma were more frequent in the leukoplakias.

Cytologic diagnosis of vaginal metastasis from renal cell carcinoma: A case report

BACKGROUND: Metastasis of renal cell carcinoma to the vagina is rare, although it may be the first evidence of the existence of the primary tumor. CASE: A metastatic deposit of renal cell carcinoma in the vagina was diagnosed by cytology as clear cell adenocarcinoma, which was confirmed by biopsy. Radiographic and ultrasound examinations confirmed the renal site of origin, which was corroborated by immunohistochemistry of the biopsy specimen. CONCLUSION: When a cytologic diagnosis of vaginal clear cell adenocarcinoma is made, metastasis of renal cell carcinoma should be considered in the differential diagnosis.

Oral lichen planus versus oral lichenoid reaction: Difficulties in the diagnosis

Lichen planus (LP) is a mucocutaneous disease with well-established clinical and microscopic features. The oral mucosa and skin may present clinical and microscopic alterations similar to those observed in LP, called lichenoid reactions (LRs), which are triggered by systemic or topical etiological agents. The difficulties faced to establish the differential diagnosis between the two pathologies were investigated in the literature. It was observed that the etiology of LP is still under discussion, with a tendency to self-immunity, while the etiology of LRs is related to the contact with specific agents, such as metallic restorative materials, resins, and drugs, allowing the establishment of a cause-effect relationship. In this case, the disease is caused by the antigen fixation in the epithelial cells, which are destructed by the immune system. Based on these data, protocols are suggested for this differentiation. The important role played by the integration between the clinician and the oral pathologist in the diagnostic process is highlighted. The treatment of LP comprises mainly the utilization of corticosteroids and the LR is treated by removal of the causal factor. Differentiation between the two diseases allows an effective and correct therapeutic approach.

Utility of sarcoma-specific fusion gene analysis in paraffin-embedded material for routine diagnosis at a specialist centre.

AIMS: Diagnosis of soft tissue sarcomas can be difficult. It can be aided by detection of specific genetic aberrations in many cases. This study assessed the utility of a molecular genetics/cytogenetics service as part of the routine diagnostic service at the Royal Marsden Hospital. METHODS: A retrospective audit was performed over a 15-month period to evaluate the diagnostic usefulness for soft tissue sarcomas with translocations of fluorescence in situ hybridisation (FISH) and reverse-transcriptase PCR (RT-PCR) in paraffin-embedded (PE) material. Results were compared with histology, and evaluated. RESULTS: Molecular investigations were performed on PE material in 158 samples (total 194 RT-PCR and 174 FISH tests), of which 85 were referral cases. Synovial sarcoma, Ewing sarcoma and low-grade fibromyxoid sarcoma were the most commonly tested tumours. Myxoid liposarcoma showed the best histological and molecular concordance, and alveolar rhabdomyosarcoma showed the best agreement between methods. FISH had a higher sensitivity for detecting tumours (73%, compared with 59% for RT-PCR) with a better success rate than RT-PCR, although the latter was specific in identifying the partner gene for each fusion. In particular, referral blocks in which methods of tissue fixation and processing were not certain resulted in higher RT-PCR failure rates. CONCLUSIONS: FISH and RT-PCR on PE tissue are practical and effective ancillary tools in the diagnosis of soft tissue sarcomas. They are useful in confirming doubtful histological diagnoses and excluding malignant diagnoses. PCR is less sensitive than FISH, and the use of both techniques is optimal for maximising the detection rate of translocation-positive sarcomas.

Refining the diagnosis and EGFR status of non-small cell lung carcinoma in biopsy and cytologic material, using a panel of mucin staining, TTF-1, cytokeratin 5/6, and P63, and EGFR mutation analysis.

INTRODUCTION: The dichotomization of non-small cell carcinoma (NSCLC) subtype into squamous (SQCC) and adenocarcinoma (ADC) has become important in recent years and is increasingly required with regard to management. The aim of this study was to determine the utility of a panel of commercially available antibodies in refining the diagnosis on small biopsies and also to determine whether cytologic material is suitable for somatic EGFR genotyping in a prospectively analyzed series of patients undergoing investigation for suspected lung cancer. METHODS: Thirty-two consecutive cases of NSCLC were first tested using a panel comprising cytokeratin 5/6, P63, thyroid transcription factor-1, 34betaE12, and a D-PAS stain for mucin, to determine their value in refining diagnosis of NSCLC. After this test phase, two further pathologists independently reviewed the cases using a refined panel that excluded 34betaE12 because of its low specificity for SQCC, and refinement of diagnosis and concordance were assessed. Ten cases of ADC, including eight derived from cytologic samples, were sent for EGFR mutation analysis. RESULTS: There was refinement of diagnosis in 65% of cases of NSCLC to either SQCC or ADC in the test phase. This included 10 of 13 cases where cell pellets had been prepared from transbronchial needle aspirates. Validation by two further pathologists with varying expertise in lung pathology confirmed increased refinement and concordance of diagnosis. All samples were adequate for analysis, and they all showed a wild-type EGFR genotype. CONCLUSION: A panel comprising cytokeratin 5/6, P63, thyroid transcription factor-1, and a D-PAS stain for mucin increases diagnostic accuracy and agreement between pathologists when faced with refining a diagnosis of NSCLC to SQCC or ADC. These small samples, even cell pellets derived from transbronchial needle aspirates, seem to be adequate for EGFR mutation analysis.

Chemotherapy induced reversible posterior leukoencephalopathy syndrome

The reversible posterior leukoencephalopathy syndrome (RPLES) is a condition characterised by reversible neurological and radiological findings that has been associated with use of immunosuppressive, chemotherapeutic and more recently novel targeted therapies. We describe the case of a 50-year-old woman with advanced non-small cell lung cancer who developed status epilepticus shortly after receiving cisplatin and gemcitabine chemotherapy. The clinical, radiological and EEG findings during and post event are presented and are in keeping with a diagnosis of RPLES. Early recognition of this rare syndrome, supportive management and withdrawal of the offending agent appear to result in a reversal of the manifestations described. © 2007 Elsevier Ireland Ltd. All rights reserved.

Carcinoma ex pleomorphic adenoma : a comprehensive review of clinical, pathological and molecular data

Carcinoma ex pleomorphic adenoma (Ca ex PA) is a carcinoma arising from a primary or recurrent benign pleomorphic adenoma. It often poses a diagnostic challenge to clinicians and pathologists. This study intends to review the literature and highlight the current clinical and molecular perspectives about this entity. The most common clinical presentation of CA ex PA is of a firm mass in the parotid gland. The proportion of adenoma and carcinoma components determines the macroscopic features of this neoplasm. The entity is difficult to diagnose pre-operatively. Pathologic assessment is the gold standard for making the diagnosis. Treatment for Ca ex PA often involves an ablative surgical procedure which may be followed by radiotherapy. Overall, patients with Ca ex PA have a poor prognosis. Accurate diagnosis and aggressive surgical management of patients presenting with Ca ex PA can increase their survival rates. Molecular studies have revealed that the development of Ca ex PA follows a multi-step model of carcinogenesis, with the progressive loss of heterozygosity at chromosomal arms 8q, then 12q and finally 17p. There are specific candidate genes in these regions that are associated with particular stages in the progression of Ca ex PA. In addition, many genes which regulate tumour suppression, cell cycle control, growth factors and cell-cell adhesion play a role in the development and progression of Ca ex PA. It is hopeful that these molecular data can give clues for the diagnosis and management of the disease.