Histologic transformation in marginal zone lymphomas†.

BACKGROUND: Histologic transformation (HT) is a poorly understood event in patients with marginal zone lymphoma (MZL). The aim of this study was to analyze incidence and risk factors for HT in a large series of MZL patients. PATIENTS AND METHODS: The studied cohort included 340 MZL patients diagnosed and treated between 1995 and 2012: 157 extranodal MZLs [mucosa-associated lymphoid tissue (MALT) lymphoma, 46%], 85 splenic MZLs (SMZLs, 25%) and 37 nodal MZLs (NMZLs, 11%). Sixty-one patients (18%) had bone marrow infiltration at presentation, with or without detectable involvement of peripheral blood, but without other involved sites; they were considered clonal B-cell lymphocytosis of marginal zone origin (CBL-MZ). RESULTS: With a median follow-up of 4.8 years, the median overall survival and progression-free survival of the whole population were 14.5 and 5 years, respectively. HT was observed in 13 cases [3.8%, 95% confidence interval (95% CI) 2%-6.5%]. Elevated lactate dehydrogenase (LDH) at diagnosis was associated with the risk of HT (P = 0.019). HT occurred in 5% of SMZLs, 4% of MALT lymphomas, 3% of NMZLs and 3% of CBL-MZ (P = 0.974). The risk of HT was 5% (95% CI 3-9%) at 5 and 10 years after diagnosis and 10% (95% CI 5%-20%) at 12 years. At the time of HT, most patients had high LDH and B symptoms. At a median follow-up of 12 months after HT, 4 of 13 patients died, all for lymphoma-related causes, with a 2-year post-transformation survival rate of 57% (95% CI 13%-86%). CONCLUSIONS: In this large retrospective series, the risk of HT across all MZL types appeared lower than the one reported for follicular lymphoma.

Analysis of the host pharmacogenetic background for prediction of outcome and toxicity in diffuse large B-cell lymphoma treated with R-CHOP21.

Knowledge on the impact of pharmacogenetics in predicting outcome and toxicity in diffuse large B-cell lymphoma (DLBCL) is scant. We tested 106 consecutive DLBCL treated with R-CHOP21 for 19 single nucleotide polymorphisms (SNPs) from 15 genes potentially relevant to rituximab-CHOP (R-CHOP) pharmacogenetics. Associations of SNPs with event-free survival (EFS) and toxicity were controlled for multiple testing. Genotypic variants of nicotinamide adenine dinucleotide phosphate (NAD(P)H) oxidase p22phox (CYBA rs4673) and alpha1 class glutathione S-transferase (GSTA1 rs3957357) were independent predictors of EFS (CYBA rs4673 TT genotype: HR 2.06, P=0.038; GSTA1 rs3957357 CT/TT genotypes: HR 0.38, P=0.003), after adjusting for International Prognostic Index (IPI). CYBA rs4673 and GSTA1 rs3957357 also predicted outcome in DLBCL subgroups by IPI. Impact of SNPs on toxicity was evaluated in 658 R-CHOP21 courses utilizing generalized estimating equations. NCF4 rs1883112 was an independent predictor against hematologic (odds ratios (OR): 0.45; P=0.018), infectious (OR: 0.46; P=0.003) and cardiac toxicity (OR: 0.37; P=0.023). Overall, host SNPs affecting doxorubicin pharmacodynamics (CYBA rs4673) and alkylator detoxification (GSTA1 rs3957357) may predict outcome in R-CHOP21-treated DLBCL. Also, NCF4 rs1883112, a SNP of NAD(P)H oxidase p40phox, may have a function in protecting against hematologic and nonhematologic toxicity. These results highlight the need to improve characterization of the host genetic background for a better prognostication of DLBCL.

Late diagnosis in severe and mild intellectual disability in adulthood.

BACKGROUND: The diagnosis of intellectual disability (ID) is highly dependent on a comprehensive personal and family medical history, a complete physical examination and a careful developmental assessment of the patient. Our study intended to: (1) classify the aetiology of mild and severe ID in an adult population of 140 Italian subjects; (2) evaluate the frequency of associated medical conditions; (3) evaluate the age of diagnosis in both groups; and (4) underline the importance of aetiological diagnosis for adult ID patients also. METHODS: The study involved 140 consecutive adult Italian ID inpatients and outpatients neurologically investigated at the Neurological Institute C. Mondino of Pavia Service for Mental Retardation. A total of 80 patients had mild ID (MID group) (39 females, 41 males), mean age 34 years (range 19-61 years), mean IQ = 64 (range 51-75), and 60 had severe ID (SID group) (32 females, 28 males), mean age 30 years (range 19-69 years). They underwent a complete diagnostic work-up that comprised prenatal, perinatal and postnatal history, physical examinations, laboratory investigations, genetic survey and neuroradiological investigations to determine the aetiology of ID and to evaluate the presence of associated medical conditions. RESULTS: ID aetiology was classified as prenatal in 34% of the MID and 28% of the SID group. Perinatal and postnatal events were found in 6% of the MID and in 5% of the SID group. Associated medical conditions were found in 97 patients (47% MID and 26% SID). A genetic diagnosis was possible in 6% of patients above 20 years of age and in 5% of patients above 40 years. A diagnosis of cerebral dysgenesis was possible in 5% of patients above 20 years and 4% of patients above 40 years. CONCLUSIONS: A long interval between the diagnosis of ID and the aetiological definition can be observed in a significant percentage (24%) of our population, leading to unfortunate consequences of late diagnosis: late onset of a specific therapeutic program, genetic counselling that is frequently no more useful, and ineffective prenatal diagnosis, leading to the birth of other affected subjects (for familiar ID).

Quality of Life Evaluation and Survival Study: a 3-yr prospective multinational study on patients with chronic respiratory failure.

Therapy of patients with chronic respiratory failure is mainly directed at minimizing symptoms in order to improve, or at least to prevent a deterioration of, patients' well-being. Under such circumstances, the perceived effect of therapies on patients' well-being and daily life represents the most important subjective outcome of treatment. Therefore, there is a need to provide a global estimate of health in patients on long term oxygen therapy or overnight home mechanical ventilation. The Maugeri Foundation Respiratory Failure Questionnaire (MRF28) is the first health status ("quality of life") questionnaire specifically developed for use in CRF and its items were selected to be applicable to patients with both obstructive and restrictive diseases. The Quality of Life Evaluation and Survival Study (QuESS) is a multinational study with the aim of re-evaluating the natural history of chronic respiratory failure in about 300 patients. To the authors knowledge, the Quality of Life Evaluation and Survival Study is the first study to evaluate the natural history of chronic respiratory failure in such a large number of subjects and with a complete set of data. In fact, both pathophysiologic and health status assessments will be made. Moreover, by collecting data on mortality, disease exacerbations and hospitalization, it will also be possible to verify the predictive ability of health status versus pathophysiology in terms of mortality and healthcare utilization.

Dirofilariasis due to Dirofilaria repens in Italy, an emergent zoonosis: report of 60 new cases.

AIMS: Sixty new cases of human dirofilariasis due to Dirofilaria repens, occurring in Italy between 1990 and 1999, are presented. This is the most extensive case study of this zoonosis reported worldwide by a single study group. The aim is to utilize this large experience to characterize the different histopathological findings in the parasitic lesions in man. METHODS AND RESULTS: Diagnosis was performed on histological sections of the nematode enclosed in the nodules excised at biopsy or surgery. The nematode was located in the subcutaneous tissue (49 cases), the epididymis (two cases), the spermatic cord (two cases), the lung (two cases), the breast (two cases), the omentum (two cases) and under the conjunctival tissue (one case). The majority of cases (46) were from Piedmont; the remainder were from Emilia-Romagna, Sardinia, Sicily, Tuscany, Apulia and Lombardy. The histopathological features of the lesions are described and the clinical and epidemiological aspects of the zoonosis are discussed. The prevalence in Italy in general and in the area of Piedmont in particular, comprising the provinces of Alessandria, Asti, Novara and Vercelli, which is one of the most severely affected areas of the world, is emphasized. The evident increase in the number of cases in the last few years is a clear indication that it is an emergent zoonosis. CONCLUSIONS: We recommend that each and every case observed be recorded, to enable the true extent of human dirofilariasis in Italy to be assessed, and that a reference centre be set up in the area to collate the data. The importance of the histopathologist's role in the diagnosis is stressed.

Rosai-Dorfman disease of the larynx.

We present a case of an 81-year-old man with a history of worsening dysphonia of six months duration. A year before a sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease) was diagnosed on a submandibular lymph node biopsy. On presentation the patient showed a mass in the left subglottic area with a modest reduction in the airway space. The patient underwent an endoscopic CO2 laser excision of the mass, without post-operative complications. Histopathological examination and electron microscope images confirmed the previous diagnosis of Rosai-Dorfman disease. The clinical and pathological features of this entity are discussed.

[Non-Hodgkin's lymphoma of the larynx: clinical cases]. / Linfoma non Hodgkin della laringe: casi clinici.

Non-Hodgkin Lymphoma (NHL) is a relatively frequent lymphatic system tumor in the head and neck region with both nodal and extranodal localizations. The larynx is one of the least frequent extranodal sites. The present study reports three cases of NHL with extranodal laryngeal localization that had recently come under observation. In these cases, the symptoms reported by the patients were aspecific and not particularly significant. Indirect macroscopic laryngoscopy and direct microlaryngoscopy did not prove pathognomonic while definitive histology clearly diagnosed lymphoma. The treatment of choice for primary laryngeal lymphoma is radiotherapy; combined chemo-radiotherapy is indicated in cases of high malignancy and in multifocal cases.

[Pleomorphic adenoma of the nasal septum]. / Adenoma pleomorfo del setto nasale.

Pleomorphic adenoma is the most frequent form of tumor in the major and minor salivary glands. It can occasionally appear in other sites corresponding to areas with ectopic salivary tissue. A case is presented of pleomorphic adenoma of the nasal septum recently observed by the authors. Complete removal of the tumor lesion, with the entire support base, careful histopathological evaluation, a battery of immunohistochemical tests and a long-term follow-up constitute the correct approach to this pathology.

[Eosinophilic gastroenteritis. A report of a clinical case]. / Gastroenterite da eosinofili. Descrizione di un caso clinico.

Eosinophilic gastroenteritis is an inflammatory pathology with an unknown etiology characterised by the presence of an eosinophil infiltrate on the intestinal wall. The symptoms (bleeding, occlusion, fistulae, etc.) may lead to surgery even if the best treatment is medical. Endoscopic examination with specific multiple biopsies is indispensable for the diagnosis of the pathology. The authors report the case of a 2-month-old baby suffering from intermittent pyloric obstruction secondary to eosinophilic gastroenteritis which was wrongly interpreted as hypertrophic stenosis of the pylorus.

Metastases to parotid gland from cancers of the upper airway and digestive tract.

Forty-four cases of parotid metastases were diagnosed and treated in the period 1968-1994. In 10 patients (23%), the primary tumour was sited in the mucosal layer of the upper airway or digestive tract: oropharynx (n=3), larynx (n=3), nasopharynx (n=2), hypopharynx (n=1) and the maxillary sinus (n=1). Histologically, the primary tumour was squamous cell carcinoma in 9 cases and adenocarcinoma in one. One patient received surgical treatment only, two patients surgery and postoperative radiotherapy, one radiotherapy only, four chemotherapy and two symptomatic treatment only. Only one patient is alive, disease-free, 5 years after treatment. The other patients died: six within 1 year, two within 2 years and one within 3 years of diagnosis.

The deep parotid lymph nodes: an anatomical and oncological study.

In order to better define the anatomical and clinical importance of the deep parotid lymph nodes, the surgical specimens obtained from a series of 18 total parotidectomies were evaluated. In 10 cases primary parotid pathology was found, whereas in the remaining eight cases metastases to glandular lymph nodes were present. One hundred and forty-nine lymph nodes, in all, were identified (range 3-14, average 8.2, mean 8), 118 located in the superficial parotid lobe (range 3-11, average 6.5, mean 7), and 31 in the deep lobe (range 0-5, average 1.7, mean 2). In the group of patients with oncological pathology, of the total 64 lymph nodes examined, 21 were found to be sites of metastasis, 11 in the superficial lobe, and 10 in the deep lobe. The above findings confirm the anatomical and oncological importance of the deep parotid lymph nodes, and highlight the necessity of a total parotidectomy in all cases in which intraglandular spread of lymph node metastases is certain or suspect.

[Myoepithelial-epithelial carcinoma of the parotid: cyto-histological description of a case]. / Carcinoma epiteliale-mioepiteliale della parotide: descrizione cito-istologic di un caso.

We report a case of epithelial-myoepithelial carcinoma of the parotid gland arised in a 72 years-old woman, in which the diagnosis was suspected on fine-needle aspiration and confirmed on surgical specimen. Immunohistochemical evidence for the dual differentiation (glandular and myoepithelial) of the tumour was obtained both on surgical specimen and cytological inclusion. Morphological features and proliferating index (MIB1) analysis suggest that this case is an intermediate grade malignant neoplasm. Main differential diagnosis of the epithelial-myoepithelial carcinoma with predominantly clear cell tumours of the salivary glands were discussed.

Renal and hepatic angiomyolipomas in a child without evidence of tuberous sclerosis.

A renal neoplasia, displaying the typical features of angiomyolipoma (an admixture of smooth muscle cells, mature adipocytes and tangles of thick-walled blood vessels) was found in a nine-year-old boy. In addition, cytoplasmic crystalloid structures and HMB 45 positivity were found in smooth muscle cells. Similar findings were also observed in a small nodule of the liver. According to literature data, angiomyolipoma is very rare in children and almost exclusively associated with tuberous sclerosis. Our case suggest that the diagnostic hypothesis of angiomyolipoma can not be disregarded when a renal mass is identified in a young patient even in a clinical setting other than tuberous sclerosis.

Angiosarcoma of the hypopharynx.

Angiosarcoma is a tumour of endothelial origin rarely found in the head and neck. A case of angiosarcoma of the pyriform sinus, treated by surgery and post-operative radiotherapy, is reported, providing a cue for discussion of the diagnostic, clinical and pathological peculiarities of the tumour in the light of personal experience and the published data.

[Aids-related cerebral lymphoma. Pathologic and immunohistochemical study of 19 cases]. / Linfomi cerebrali AIDS-correlati. Studio patologico ed immunoistochimico di 19 casi.

We studied 19 cases of AIDS-related cerebral lymphomas, 15 of which are primary, and 4 secondary to systemic lymphoma. Eighteen cases are classified as non-Hodgkin's B cell lymphomas; in 1 case, an anaplastic large cell lymphoma coexists with systemic Hodgkin's disease. High-grade histologic types predominate (centroblastic, immunoblastic and immunoblastic plasmocytoid). One case of angiotropic lymphoma is included solely localized to the brain. We describe clinical and radiological features, gross, microscopic and immunophenotypic appearances. Other HIV-related associated diseases of the central nervous system are also considered.

[Parotid metastases: a review of the literature and case reports]. / Le metastasi parotidee: revisione della letteratura e contributo casistico.

Parotid gland is an unusual metastasis site. Metastatic lesions very often represent spread from adjacent regions of lymphatic drainage; nevertheless direct involvement or hematogenous spread can occur. Head and neck cutaneous tumors are the most common primary: in a overlooking of more than 800 cases, cutaneous squamous cell carcinomas and melanomas represent about 80%. Parotid metastasis from extra-cutaneous head and neck tumors and distant primary are uncommon: in our review we found respectively 66 and 87 reports. In our experience, from 1968 to 1991, we observed 38 patients with metastatic involvement of the parotid gland. The primary were located as follows: 24 cutaneous head and neck tumors (15 SCC, 7 melanomas, 2 BCC), 10 extra-cutaneous supra-clavicular tumors (9 carcinomas, 1 adenocarcinoma), 4 distant primary (2 renal cell carcinomas, 2 lung tumors). In 14 patients was performed a parotidectomy, in 10 cases associated to a neck dissection and in 4 cases followed by post-operative radiotherapy. Exclusive radiotherapy and chemotherapy were performed respectively in 14 and 4 cases, in 6 patients the only planned treatment was a symptomatic therapy. After 1, 3 and 5 years follow-up the overall survival was respectively of 71.4%, 30.4% and 11.8%; better results were observed in cutaneous primary (86.3%, 42.8% and 20%). To conclude, parotid metastases represent a not uniform clinical entity. Cutaneous SCC, BCC and melanoma can be successfully treated by surgery and/or radiotherapy. As non-cutaneous secondary parotid tumors have a poor prognosis, treatment must be related to condition of generalized disease.

Parenchymal renal involvement in three cases of non-Hodgkin lymphomas: clinical and pathological features.

Parenchymal neoplastic invasion of the kidneys is a common postmortem finding in patients who have died from advanced non Hodgkin's lymphomas (NHL). However, it rarely causes major clinical consequences, such as impairment of glomerular and tubular function, acute or rapidly progressive renal failure. Renal involvement is even less frequent as a first manifestation of NHL, the so-called "primary" renal lymphoma. A review of the main clinical, diagnostic and pathological aspects of three cases observed in our division is presented here.

[The CNS in AIDS and in asymptomatic HIV positive patients]. / Das ZNS bei AIDS und bei asymptomatischen HIV-Trägern.

Neuropathological investigations were carried out on 166 autopsies of HIV-seropositive patients, with and without AIDS. Opportunistic infections and lymphomas were present in about 50% of cases; 65 patients were bearers of HIV-encephalopathy. HIV core protein p24 was detected in few mono- and multinucleated macrophages (HIV-cells), only in cases with HIV-encephalopathy. In the CNS of HIV-positive, asymptomatic patients no histological or immunohistochemical abnormalities were seen. These findings let suppose that AIDS-Dementia is a result of a late infiltration of HIV-infected macrophages from the bloodstream into the brain and not due to an impairment of neuronal or glial cells infected by HIV in the early stages of the disease.