New guidelines for treating major depression

A case of acanthosis nigricans associated with a metastatic adenocarcinoma is presented. To our knowledge this is the first one reported in the literature. The primary tumour is unknown, but it is presumably a cholangiocarcinoma. The skin changes preceded the detection of malignancy by 2 years, during which the skin lesions progressed though the patient was still in good health. If malignant acanthosis nigricans is suspected and the underlying malignancy cannot be found at the initial screening, repeated screenings are necessary because of the time factor.     

Case report: defective beta and alpha cell regulation in patients with hyperinsulinemia and acanthosis nigricans

Beta cell hypersecretion is associated with the syndrome of hyperandrogenism, insulin resistance, and acanthosis nigricans. It is unknown whether concomitant alpha cell secretory dysfunction occurs in patients with this syndrome. The authors evaluated the gastroenteropancreatic hormones in four family members with varying degrees of the hyperandrogenism, insulin resistance, and acanthosis nigricans syndrome. Gastroenteropancreatic hormones were measured during oral glucose tolerance test with and without subcutaneous octreotide injection. The study revealed that the administration of subcutaneous octreotide resulted in suppression of beta cell function (insulin and c-peptide) but had no effect or a delayed effect on alpha cell secretion (glucagon). Furthermore, the severity of glucagon abnormalities paralleled that of beta cell hypersecretion and the clinical and phenotypic manifestations of acanthosis nigricans in our four patients. We speculate that this alpha cell aberration could potentially be involved in the altered glucose homeostasis and perhaps the skin manifestations of this syndrome. Therefore, glucagon levels should be evaluated in the hormonal studies in patients with hyperandrogenism, insulin resistance, and acanthosis nigricans syndrome.     

Radiological manifestations of oesophageal involvement in acanthosis nigricans

Radiologic features of two cases of acanthosis nigricans with oesophageal involvement are reported. The first case demonstrated diffuse, granular shadows throughout the oesophagus which were difficult to differentiate from oesophageal moniliasis. Another case showed many discrete and tiny elevations resembling pseudopolyposis of the colon. Emphasis is placed on radiological differential diagnosis from moniliasis and leukoplakia of the oesophagus.     

Detection of Francisella tularensis by the polymerase chain reaction

A 27-year-old woman and a 13-year-old girl diagnosed with juvenile dermatomyositis in childhood developed clinical findings of partial lipodystrophy 10 years after diagnosis. Exhaustive clinical and laboratory examinations showed an association with other abnormalities: hypertrichosis, steatohepatitis, and an abnormal insulin response to the glucose loading test in the first patient. Hypertrichosis, steatohepatitis, insulin-resistant diabetes mellitus, and acanthosis nigricans were observed in the second patient. Renal function was normal in both patients. Although a localized form of lipodystrophy has been reported associated with connective tissue disease (connective tissue lipoatrophy), the partial form has been infrequently described in association with juvenile dermatomyositis.     

Unilateral epidermal naevus resembling acanthosis nigricans

A man born with a unilateral epidermal naevus on the right side of the abdomen developed at puberty symmetrical benign acanthosis nigricans in the body folds. The symmetrical eruption later disappeared completely. The unilateral epidermal naevus and the symmetrical eruption showed identical histological features, i.e. those of acanthosis nigricans. At the age of 32 he developed a muco-epidermoid cancer of the left parotid gland. A decision whether the association of unilateral epidermal naevi with malignant tumours occurs with unusual frequency requires (a) a long follow-up of the patient with the unilateral naevus, (b) a differentiation of the unilateral eruption from unilateral malignant acanthosis nigricans and (c) statistical evidence.     

Combined bilateral submandibular and sublingual swelling, macroglossus, and carpal tunnel syndrome caused by light chain amyloidosis

Three cases of light chain kappa amyloidosis in multiple myeloma patients are described with remarkable involvement of the tongue and swelling of the sublingual and submandibular regions, and without signs of nephropathy despite Bence Jones kappa proteinuria. All three patients had carpal tunnel syndrome at the beginning of their disease course and only moderate gastrointestinal involvement. Primarily for prognostic reasons, amyloidosis should be suspected in such cases, even in the presence of these highly unusual manifestations, and the diagnosis should be confirmed by unambigously-positive biopsies.     

Three monoclonal IgG components, an IgG4(lambda), an IgG2(kappa) and an IgG1/IgG3 (kappa) Gm(f,b) hybrid, in a single myeloma patient

An unusual triclonal IgG combination in the serum of a 56-year old male with clinical stage IIIB multiple myeloma is reported. The patient initially had an IgG4(lambda) monoclonal protein in his serum and later developed an IgG2(kappa) and an IgG (kappa) which possessed the characteristics of both IgG1 and IgG3 subclasses with an unusual combination of allotypic markers. Three M-proteins did not share idiotypic determinants. A rare class-switch recombination followed by mutation has been considered as a possible mechanism leading to this combination.     

Primary plasmacytoma of lymph nodes

Primary plasmacytoma of the lymph nodes is very rare, and there are fewer than 20 reported cases. These cases appeared to have a better prognosis than other extramedullary plasmacytomas, with rare recurrence and no progression to myeloma after treatment. To better characterize the clinicopathological features and the pathogenesis of primary plasmacytoma of the lymph nodes, we reviewed our consultation files and retrieved seven such cases. The age of presentation ranged from 39 to 76 years (median age, 59 years), with three women and four men. The clinical follow-up varied from 1 to 14 years. All patients presented with enlarged lymph nodes and had an indolent clinical course, except for one patient with slow progression and increasing numbers of bone marrow plasma cells. Five patients were treated with excision only and two with excision and chemotherapy. None of the patients had recurrence or developed multiple myeloma. All cases showed immunoglobulin light chain restriction, four with monotypic lambda and three with monotypic kappa. One patient had extensive nodal amyloid deposition. Four cases had monoclonal heavy chain expression, three with monoclonal immunoglobulin (Ig) G and one with monoclonal IgM. All cases were negative for CD20 and CD43, and six cases expressed CD79a. Overexpression of p53 and bcl-2 was not detected by immunostaining in any of the cases. Epstein-Barr viral (EBV) RNA was not detected in all seven cases by in situ hybridization, and no Kaposi's sarcoma-associated herpesvirus (KSHV) DNA sequences were detected by polymerase chain reaction in five cases. Our results confirm a more favorable outcome and rare progression to multiple myeloma in primary nodal plasmacytomas after excision or chemotherapy. The results of oncoprotein and viral studies suggest that the pathogenesis of primary nodal plasmacytoma may not be due to bcl-2- and p53-associated changes or viral-induced changes by EBV and KSHV.     

Advanced glycation endproducts stimulate mitogen-activated protein kinase and proliferation in rabbit vascular smooth muscle cells

Two patients with plasma cell leukemia (PCL) with a t(11;14)(q13;q32) translocation are reported. Case 1 is a 64-year-old woman diagnosed as having primary PCL (IgA/lambda, Stage III) with high serum LDH and beta 2-microglobulin (beta 2MG) levels. She was treated with combination chemotherapy but died of gastrointestinal bleeding on the 45th hospital day. Case 2 is a 52-year-old man, initially diagnosed with multiple myeloma (IgG/kappa, Stage III) in August 1993. Relapse several months after primary chemotherapy was characterized by a rapid increase in plasma cells in peripheral blood, high serum LDH and beta 2MG levels, and resistance to further chemotherapy. Both cases showed complex karyotypic abnormalities including t(11;14), and Northern analysis revealed overexpression of the PRAD1/ cyclin D1 gene. The PRAD1 gene is found on chromosome band 11q13 and encodes cyclin D1. Cyclin D1 plays an important role in control of the cell cycle, and overexpression of PRAD1/cyclin D1 may be involved in disease progression in these cases.     

Clinical evaluation of myeloma osteoclastic bone lesions: II. Induced hypocalcemia test using salmon calcitonin

Acute effects of salmon calcitonin (SCT) were tested by an SCT induced hypocalcemia test (SCT delta Ca test) in 70 cases of multiple myeloma (MM) (including 52 untreated patients) with bone involvement. Response to SCT in terms of maximum induced hypocalcemia (M delta Ca) was compared to normal controls (NC) and correlated with the main presenting features and clinical status. Acute effects are significantly more marked in MM than in NC (p less than .001). There is a good correlation with the extent of lytic bone lesions (p less than .01), the presence of hypercalcemia (p less than .02) and the myeloma cell mass (p less than .05). After correction for bone involvement response to SCT (M delta Ca) was stronger in IgA lambda MM than in IgG kappa (p less than .01). It is of particular interest that acute effects are significantly more marked in cases of active disease than in non-active disease. We conclude that the SCT delta Ca test might be of practical value in the management of MM.     

B-cell lymphoma of mucosa-associated lymphoid tissue of the thymus: a report of two cases with a background of Sj?gren's syndrome and monoclonal gammopathy

Two rare cases of low-grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) arising in the thymus are reported. Both patients (a 61-year-old man and a 75-year-old woman) were suffering from Sj?gren's syndrome and immunoglobulin (Ig)A kappa monoclonal gammopathy. Mixed IgA-IgG cryoglobulinemia was also present in the male case. Tumor cells expressed IgA and kappa antibody reactive proteins identical with serum IgA kappa M. Moreover, we could demonstrate rearrangements of the immunoglobulin heavy and light chain genes, which supported the monoclonal origin of tumor cells. Immunological abnormalities improved after thymectomy in one case in which the tumor cells were confined to the thymus, but not the other with regional lymph node involvement, suggesting a causal role for the tumor. MALT lymphomas of the thymus thus appear to be associated with immunological disorders such as Sj?gren's syndrome or monoclonal gammopathy.     

The arts and humanities: a creative approach to developing nurse leaders

There is still much controversy about the precursor cell type in multiple myeloma (MM). Some authors claim that it is a pre-B cell, others state that it is a memory B cell or plasmablast. We have recently shown that the VDJ region of the MM immunoglobulin heavy chain gene is somatically hypermutated and antigen selected, without intraclonal variation or evolution in time. By using a patient-specific PCR approach we have now obtained evidence that the premyeloma cell can be situated in the pre-switched B-cell compartment and that heavy chain switching can occur without further somatic mutation. Based on the MM immunoglobulin sequences derived from the bone marrow, patient-specific CDR2 and CDR3 oligonucleotides were designed. B lymphocytes were separated from plasma cells based on the expression of CD19 and HLA class II or surface bound IgM using immunomagnetic beads. The expressed Ig sequences were amplified by RT-PCR using patient specific CDR2 primers and isotype specific primers (C mu, C gamma, and C alpha). Myeloma-specific Ig sequences were detected by a myeloma-specific CDR3 probe and sequenced. In one out of five cases we found in the peripheral blood clonally related IgM and IgA sequences with the same somatic mutations as the MM-IgG sequence. In another case of an IgG MM we found in the bone marrow clonally related IgA sequences with the same somatic mutations. These findings, together with the fact that myeloma-Ig genes contain somatic mutations without intraclonal variation, suggest that the clonogenic cell in multiple myeloma can originate from a pre-switched but somatically mutated B cell.     

Clinicopathologic findings in the Bannayan-Riley-Ruvalcaba syndrome

BACKGROUND: The term Bannayan-Riley-Ruvalcaba syndrome has been proposed to reflect the clinical overlap of 3 conditions previously described as separate entities, each inherited in an autosomal dominant fashion. They are the Riley-Smith, Bannayan-Zonana, and Ruvalcaba-Myhre-Smith syndromes. OBSERVATIONS: We studied 2 kindreds with the Bannayan-Riley-Ruvalcaba syndrome. Characteristic cutaneous findings included multiple subcutaneous lipomas and vascular malformations, lentigines of the penis and vulva, verrucae, and acanthosis nigricans. Macrocephaly with normal ventricular size, mental retardation, central nervous system vascular malformations, intestinal polyposis, skeletal abnormalities, and thyroid tumors were the most common systemic featues. A striking clinical finding in 1 patient was widespread verrucous changes of both lips that histologically showed epidermal hyperplasia with papillomatosis and hyperkeratosis. Biopsy specimens of facial papules demonstrated the histological features of both syringomas and trichilemmomas. Lentiginous hyperplasia of the epidermis with increased pigment in the basal layer and a slight increase in the number of melanocytes were seen in biopsy specimens of the penile lentigines. CONCLUSIONS: The histologic findings of both the facial lesions and the pigmented macules of the penis in the Bannayan-Riley-Ruvalcaba syndrome have not, to our knowledge, been reported previously. The similarities between the Bannayan-Riley-Ruvalcaba syndrome and Cowden disease raise the possibility of a common genetic pathogenesis for these 2 diseases.     

Monoclonal heavy chain (immunoglobulin G3) deposition disease: report of a case

Seven cases of nonamyloid heavy chain (gamma chain) deposition disease have been previously reported. We describe one case of a 79-year-old woman presenting with proteinuria and microscopic hematuria whose renal biopsy showed nodular glomerulosclerosis with deposition of gamma3 heavy chains and complement in the glomeruli and tubular basement membranes with no associated light chain deposition. The patient did not have multiple myeloma. This case is unique in that in all previously reported cases of heavy chain deposition disease the gamma chain subtype has been either gamma1 or gamma4.     

Infantile perianal pyramidal protrusion

BACKGROUND: The number of reported cases of infantile perianal eruption has been increasing. However, infantile pyramidal protrusion located in the midline anterior to the anus has apparently been reported mainly as acrochordons or skinfolds. OBSERVATIONS: Fifteen infants (14 girls and 1 boy) had a pyramidal protrusion located only in the midline anterior to the anus. Histological examination revealed acanthosis in the epidermis, marked edema in the upper dermis, and mild infiltrates in the dermis. The patients had been brought to the hospital because of swelling of the protrusion. However, all protrusions showed reduction without any treatment. CONCLUSION: Infantile pyramidal protrusion located only in the midline anterior to the anus should be distinguished from acrochordons or skinfolds based on the characteristic clinical features.     

Multiple myeloma presenting as parasellar syndrome and cranial nerve palsies

Cranial and intracranial locations have been rarely reported in multiple myeloma. Their occurrence as a harbinger of multiple myeloma seems to have a particular significance. In this report, we discuss a case of multiple myeloma presenting as parasellar syndrome and cranial nerve palsies. A 75-year-old woman was admitted to the hospital in June, 1994, with a 3-month history of headache and a 3-week history of diplopia and photophobia. Physical examination revealed right third, fourth and sixth cranial nerve palsies. MRI scan demonstrated a homogeneous, voluminous mass, isointense in T1-weighted images with the cerebral parenchyma and hyperintense in T2-weighted images, occupying the sphenoid sinus and extending within the sella turcica and right cavernous sinus. Lying above the mass and apparently separated from it by a thin rim of hypointensity was a normal pituitary gland. X rays revealed destructive changes of the sella turcica. A minimal disturbance of endocrine function together with a radiologically abnormal pituitary fossa indicated that the primary lesion might lie outside the pituitary fossa. A diagnosis of IgG-kappa type multiple myeloma was made by pertinent laboratory studies. She received local radiation to the intracranial mass (50 Gy) and conventional chemotherapy. Sixteen months after the therapy she is in good health.     

Paraproteinaemic neuropathies

Paraproteinaemia and neuropathy are each relatively frequent and may be associated by chance. However, a number of significant relationships have to be ruled out in the differential diagnosis. Malignant gammopathy should be excluded: multiple myeloma can lead to compression of the spinal cord or cauda equina; primary amyloidosis is occasionally involved; the rare but intriguing POEMS syndrome, consisting of polyneuropathy, organomegaly, endocrinopathy, M-protein and skin changes, usually accompanies osteosclerotic myeloma. It can be associated with angio-follicular lymph node hyperplasia and needs to be recognized because radioablative therapy is curative. The 'benign' monoclonal gammopathies of undetermined significance, known as MGUS, are much more frequent. There is an IgM MGUS group with predominantly distal sensorimotor demyelinating polyneuropathy and another rather heterogeneous group with IgG or IgA MGUS and a tendency to a favourable response to plasmapheresis. The role of the monoclonal IgG and IgA antibodies is unclear. This chapter has focused on the pathogenetic mechanisms of neuropathies associated with IgM MGUS. In the majority of cases, monoclonal autoantibodies specific for particular carbohydrate epitopes bind to myelin and are now recognized as the primary cause of the disease manifestations, including widening of the myelin lamellae. While the autoantibodies have been shown to bind complement, the presence of inhibitors is invoked to explain the absence of acute inflammatory changes. The epitopes recognized with the highest affinity by the auto-antibodies are present on the myelin-associated glycoprotein (MAG) and could interfere with cell adhesion and cellular signally processes. In addition, binding to antigenically similar glycoproteins, such as PO, PMP-22 and some acidic glycolipids, may be a contributory factor. It is generally accepted that the anti-MAG autoantibodies are inducing a progressive demyelinating polyneuropathy by modifying axon-Schwann cell interactions.     

Morphological changes of the accessory male sexual glands of rats treated with estrogens during neonatal period

The first case of oral hairy leukoplakia in an HIV-negative patient with multiple myeloma is reported. The patient is a 56-year old man who has had monoclonal gammopathy of undetermined significance since 1986 and has been treated for a symptomatic multiple myeloma since 1993. The clinical and histopathologic findings are typical for oral hairy leukoplakia, and Epstein-Barr virus was demonstrated with polymerase chain reaction technique. Although a relatively large number of cases of oral hairy leukoplakia has been reported in HIV-negative patients, both immunocompromised and immunocompetent, only a few of these patients have had a malignant hematologic disease.     

Acquired amylase production induced by radiotherapy in a myeloma patient

A 55-year-old patient with multiple myeloma (IgG-lambda) diagnosed in November 1988 was admitted because of bone pain throughout the body. After plasmapheresis and several courses of chemotherapy, a massive tumor of the left thoracic wall involving the rib appeared. Radiotherapy was performed to ameliorate the severe chest pain, after which myelomatous pleural effusion appeared on the left side. The serum, urine and pleural effusion revealed increased activity of amylase of the salivary type. Amylase activity was also detected in the supernatant of myeloma cells cultured from pleural effusion. We reviewed 12 cases of ectopic amylase-producing multiple myeloma. All the cases except one have been reported from Japan, and hyperamylasemia in these cases was detected at diagnosis or during course of the illness. Moreover, cytogenetic analysis of myeloma cells of previous reports revealed structural abnormalities including chromosome 1, near the amylase gene locus. This case also showed t (1; 10) (q 21?; q 26) by examination of 8 metaphase derived from bone marrow. These observations suggested that ectopic amylase production was induced by irradiation to the plasmacytoma of thoracic wall.     

Kappa and lambda light chain proteins--clinical and prognostic significance in patients with multiple myeloma

In 76 patients with multiple myeloma an independent or combined light chain production at a ratio of kappa (kappa) to lambda (lambda) chains of 43:33 was proved. Two groups of patients were formed depending on the type of the light chain production. They were compared by a number of biological, clinical and biochemical parameters, which demonstrate the frequency and pathogenetic participation of the two light chains in the main syndromes of the disease. The therapeutic response and prognostic value were also estimated. Bence Jones (lambda) chains prevail in men, in the III clinical stage of the disease, in patients with tubular proteinuria and in syndromes indicating an advanced stage of evolution of the main process, in non-reversible azotaemia, hypercalcaemia and hypoalbuminemia. The survival rate in thus group of patients is an average of 7 months shorter in comparison with the BJ (kappa) group (the difference is non-significant). The median survival of patients with BJ (kappa) is 30 months and 21 months for BJ (lambda).