Nodular Aggregates Research Articles

An Unusual Apocrine Carcinoma on the Forehead

We herein report an unusual case of apocrine carcinoma on the forehead. The lesion was formed by the anastomosis of numerous tubular structures with widespread decapitation secretion, thus demonstrating apocrine differentiation. However, we observed some unusual histopathologic features that differed from those found in typical examples of apocrine ductal carcinoma, namely: 1) a relatively well-circumscribed lesion in the dermis, and 2) nodular or solid aggregations composed of basaloid cells. We believe the present case is an apocrine ductal carcinoma, although it has a nodular appearance and basaloid cells. Otherwise, it could be a hitherto undescribed variant of apocrine carcinoma. This apocrine carcinoma on the forehead may have originated from either pluripotential cells or from apocrine glands at an unusual site.

Severe dysphagia in lower cranial nerve involvement as the initial symptom of Wegener's granulomatosis

We observed a 42-year-old woman presenting with severe dysphagia secondary to paralysis of the lower cranial nerves and right phrenic nerve involvement, followed by respiratory failure. An EMG confirmed bilateral denervation of the 9th, 10th, 11th and 12th cranial nerves and right phrenic nerve. Videolaryngoscopy showed bilateral vocal fold immobility. Anemia, elevated ESR, microhematuria and C-ANCA (PR-3) antibodies were detected. Brain MRI and CSF were normal. A chest CT showed bilateral, irregular pulmonary lesions. An 18F-FDG total body scan showed diffuse hypermetabolic regions in both pulmonary bases, in the mediastinic region and in the rhinopharynx, raising the suspicion of a neoplastic process. A transthoracic biopsy disclosed nodular granulomatous aggregates with multinucleated giant cells, supporting the diagnosis of Wegener's granulomatosis. Immunosuppressive therapy achieved complete clinical resolution and cleared the pulmonary lesions. To the best of our knowledge this is the first report of Wegener's granulomatosis presenting with neurogenic dysphagia due to lower cranial nerve palsy.

Pigmented villonodular synovitis : Dorsum foot

Plasmacytoid dendritic cell neoplasms manifest in two clinically and pathologically distinct forms. The first variant is represented by nodular aggregates of clonally expanded plasmacytoid dendritic cells found in lymph nodes, skin, and bone marrow ('Mature plasmacytoid dendritic cells proliferation associated with myeloid neoplasms'). This entity is rare, although likely underestimated in incidence, and affects predominantly males. Almost invariably, it is associated with a myeloid neoplasm such as chronic myelomonocytic leukemia or other myeloid proliferations with monocytic differentiation. The concurrent myeloid neoplasm dominates the clinical pictures and guides treatment. The prognosis is usually dismal, but reflects the evolution of the associated myeloid leukemia rather than progressive expansion of plasmacytoid dendritic cells. A second form of plasmacytoid dendritic cells tumor has been recently reported and described as 'blastic plasmacytoid dendritic cell neoplasm'. In this tumor, which is characterized by a distinctive cutaneous and bone marrow tropism, proliferating cells derive from immediate CD4+CD56+ precursors of plasmacytoid dendritic cells. The diagnosis of this form can be easily accomplished by immunohistochemistry, using a panel of plasmacytoid dendritic cells markers. The clinical course of blastic plasmacytoid dendritic cell neoplasm is characterized by a rapid progression to systemic disease via hematogenous dissemination. The genomic landscape of this entity is currently under intense investigation. Recurrent somatic mutations have been uncovered in different genes, a finding that may open important perspectives for precision medicine also for this rare, but highly aggressive leukemia.

Erythema Nodosum

Erythema nodosum is the most frequent clinicopathologic variant of panniculitis. The process is a cutaneous reaction that may be associated with a wide variety of disorders, including infections, sarcoidosis, rheumatologic diseases, inflammatory bowel diseases, medications, autoimmune disorders, pregnancy, and malignancies. Erythema nodosum typically manifest by the sudden onset of symmetrical, tender, erythematous, warm nodules and raised plaques usually located on the lower limbs. Often the lesions are bilaterally distributed. At first, the nodules show a bright red color, but within a few days they become livid red or purplish and, finally, they exhibit a yellow or greenish appearance, taking on the look of a deep bruise. Ulceration is never seen, and the nodules heal without atrophy or scarring. Histopathologically, erythema nodosum is the stereotypical example of a mostly septal panniculitis with no vasculitis. The septa of subcutaneous fat are always thickened and variously infiltrated by inflammatory cells that extend to the periseptal areas of the fat lobules. The composition of the inflammatory infiltrate in the septa varies with age of the lesion. In early lesions edema, hemorrhage, and neutrophils are responsible for the septal thickening, whereas fibrosis, periseptal granulation tissue, lymphocytes, and multinucleated giant cells are the main findings in late stage lesions of erythema nodosum. A histopathologic hallmark of erythema nodosum is the presence of the so-called Miescher's radial granulomas, which consist of small, well-defined nodular aggregations of small histiocytes arranged radially around a central cleft of variable shape. Treatment of erythema nodosum should be directed to the underlying associated condition, if identified. Usually, nodules of erythema nodosum regress spontaneously within a few weeks, and bed rest is often sufficient treatment. Aspirin, nonsteroidal antiinflammatory drugs, such as oxyphenbutazone, indomethacin or naproxen, and potassium iodide may be helpful drugs to enhance analgesia and resolution. Systemic corticosteroids are rarely indicated in erythema nodosum and before these drugs are administered an underlying infection should be ruled out.

Development of a Richter syndrome with a monoclonal component from a true B-cell chronic lymphocytic leukemia (B-CLL) treated with fludarabine

Dear Editor, B-cell chronic lymphocytic leukemia (B-CLL) patients with unmutated IgV genes frequently show trisomy 12 and a poor clinical outcome, while those with mutated IgV genes often show 13q14 deletions (13q−) and a favorable prognosis [1]. A small B-CLL proportion may present with a serum monoclonal component and lympho-plasmacytoid elements, distinguishable from those CD5− and CD23− cells of lympho-plasmacytoid lymphoma [2]. Fludarabine is a very effective drug for the treatment of B-CLL [3] and indolent lymphomas [4]. However, it is associated with decreased immuno-surveillance determining a high incidence of opportunistic infections and secondary cancers [5]. Moreover, the occurrence of a large B-cell lymphoma, referred to as Richter’s syndrome (RS), is one possible natural evolution even in untreated B-CLL patients [6]. Herein, we report on a 58-year-old woman in apparent good health who came to our clinic for evaluation because of the incidental discovery of hyperleucocytosis. Her clinical parameters and biological findings at diagnosis and during the follow-up are summarized in Table 1. She never showed any monoclonal component in either serum or urine samples; however, 1 month after the fourth course of fludarabine dual monoclonal components (12.0 g/dl), both typified as IgG kappa were detected in the serum (Fig. 1c and d). On admission to our ward, a lymphnode biopsy demonstrated the complete disruption of the normal architecture by a lymphomatous B-cell population, which presented a parafollicular and nodular pattern of infiltration. This cell population was formed by small mature B-cells, lympho-plasmacytoid elements and plasma cells, prolymphocytes and paraimmunoblasts. These last cells were grouped in nodular aggregates, that constituted 24% of the entire cell population. In conclusion, the lymphnode histology pointed to a B-CLL in RS evolution. On clinical diagnosis and during the follow-up, flourescent in situ hybridization (FISH) was always performed with the CLL probe panel, including the following five multicolor probes: LSI p53/LSI ATM/LSI D13S319/LSI 13q34/CEP 12 (Vysis, Downers Grove, IL, USA). At diagnosis, loss of one D13S319 locus was revealed in 48% of marrow cells (Fig. 1e), whereas upon progression, the same locus was Ann Hematol (2007) 86:619–622 DOI 10.1007/s00277-007-0281-y

Characterization of surface‐modified hollow fiber polyethersulfone membranes prepared at different air gaps

AbstractHollow fibers were spun from a solution of surface‐modifying macromolecule blended polyethersulfone in dimethyl acetamide by using dry‐wet spinning method at different air gaps and at room temperature. The air gap was varied from 10 to 90 cm. The ultrafiltration performance of hollow fibers was studied by using aqueous solutions of polyethylene glycols and polyethylene oxides of different molecular weights. Significant difference in surface morphology between the inner and outer surface of the hollow fibers was observed by atomic force microscopy (AFM). Similar results were obtained by contact angle measurement and XPS. Mean pore sizes of the inner surface and outer surface were calculated from AFM images and compared with the pore sizes obtained from mass transport data. Pore size distribution curves were drawn from both data, i.e., from AFM images and mass‐transport data, both methods gave similar results. Roughness parameters of the inner and outer surfaces and the sizes of nodular aggregates on both surfaces were measured. An attempt was made to correlate the above parameters with the performance of the membranes. Unexpected values of contact angles of both inner surface and outer surface were obtained. It was observed that the studied membranes could be put into two groups: (i) the membranes fabricated between 10 and 50 cm air gap and (ii) fabricated at higher than 50 cm air gap. A plausible mechanism for the unexpected results was discussed. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 104: 710–721, 2007

Human mesenchymal stem cells isolated from bone marrow and lymphoid organs support tumor B-cell growth: role of stromal cells in follicular lymphoma pathogenesis

AbstractAccumulating evidence indicates that the cellular microenvironment plays a key role in follicular lymphoma (FL) pathogenesis, both within tumor lymph nodes (LNs) and in infiltrated bone marrow where ectopic LN-like reticular cells are integrated within malignant B-cell nodular aggregates. In normal secondary lymphoid organs, specific stromal cell subsets provide a highly specialized microenvironment that supports immune response. In particular, fibroblastic reticular cells (FRCs) mediate immune cell migration, adhesion, and reciprocal interactions. The role of FRCs and their postulated progenitors, that is, bone marrow mesenchymal stem cells (MSCs), in FL remains unexplored. In this study, we investigated the relationships between FRCs and MSCs and their capacity to sustain malignant B-cell growth. Our findings strongly suggest that secondary lymphoid organs contain MSCs able to give rise to adipocytes, chondrocytes, osteoblasts, as well as fully functional B-cell supportive FRCs. In vitro, bone marrow–derived MSCs acquire a complete FRC phenotype in response to a combination of tumor necrosis factor-α and lymphotoxin-α1β2. Moreover, MSCs recruit primary FL cells that, in turn, trigger their differentiation into FRCs, making them able to support malignant B-cell survival. Altogether, these new insights into the cross talk between lymphoma cells and their microenvironment could offer original therapeutic strategies.

The challenging patient: HCV and alcoholic liver disease

A 54-year-old man first learned that he had liver disease 5 years ago. He was complaining of aches and pains when his wife noticed that his eyes had turned yellow. He presented to the emergency room and was referred to the transplant evaluation clinic. Liver transplantation evaluation confirmed that the patient was infected with hepatitis C virus (HCV) genotype 1a. The viral copy number was 1.4 million copies/mL HCV RNA. In addition to jaundice, he had ascites and mild encephalopathy. He had been married for 25 years with 2 children. In the past he worked in construction, but he had not been able to work for 2 years before his initial presentation because of chronic back pain. Before recognition of liver disease, his normal pattern was to drink 2-4 beers a day. He answered negatively to all 4 CAGE questions. He stopped all alcohol when he was given the advice to stop on account of liver disease. He had no reaction to stopping alcohol. He had a history of one conviction for driving while impaired 25 years ago. He went to drivers education classes to get his license back. He agreed that he had “experimented” with intravenous drugs when he was a teenager. He was also tattooed when he was 18. There is a history of probable alcoholism affecting his mother. Antiviral therapy was not attempted, and the patient was placed on the transplant waiting list. Four years ago, he underwent orthotopic liver transplantation. Histopathological examination of the explanted liver revealed micronodular cirrhosis without neoplasm. He received posttransplantation immunosuppression with tacrolimus, mycophenolate mofetil, and prednisone. He had no episodes of acute cellular rejection. Fifteen months after the transplant, when his immunosuppression had been reduced to just tacrolimus, he was treated with pegylated interferon alfa-2a and ribavirin. He was unable to tolerate this because of depression and because of “feeling terrible.” It was stopped after 8 weeks. Two years ago, results of a percutaneous liver biopsy showed one core of hepatic tissue with 14 portal tracts. The portal tracts contained moderate inflammation, comprising mostly lymphocytes and plasma cells, with occasional eosinophils and neutrophils. A few nodular lymphoid aggregates were also seen. There was mild interface hepatitis. One to 3 necroinflammatory foci were found per lobule. Occasional ballooned hepatocytes and acidophil bodies were seen. The parenchyma was negative for marked steatosis, Mallory hyaline, cholestasis, alpha-1 antitrypsin-like globules, and iron deposits. A Trichrome-stained slide showed portoportal fibrous bridging with rare portocentral fibrous bridging. There was mild pericellular fibrosis. In summary, these histopathological appearances were characterized as chronic HCV, grade 2, stage III, with mild pericellular fibrosis. For the past year, his main problem has been recurrent persistent intractable ascites. He underwent a transjugular intrahepatic portosystemic shunt placement 3 months ago. He was admitted to the hospital 2 months ago with encephalopathy. He was treated with increased lactulose, and although the symptoms improved, they did not resolve completely.

Evidence of reworking and resuspension of carbonates during last glacial maximum and early deglacial period along the southwest coast of India

A gravity core collected from the upper slope of southwest of Quilon at a water depth of 776 m (Lat: 8°12′263″N, Long: 76°28′281″E) was analysed for texture (carbonate free), calcium carbonate and organic carbon. Variation in silicic fraction seems to be controlled by silt, i.e., enrichment from 15 ka BP to 10 ka BP and then constant in Holocene. Below 15 ka BP, the silicic fraction gets depleted compared to the Holocene section with a minimum around 21 ka BP. Clay content remains nearly constant except in the Holocene where it shows an enrichment. Carbonate content of less than 63 micron when computed by subtracting coarse fraction content from the total carbonate suggests that the total carbonates are mainly concentrated in the finer fraction. All these carbonate phases show an inverse relationship with silicic fraction except in Holocene. Below 15 ka BP, CaCO3 dominates in sediments comprising more than 65%, such an increase is also seen in the coarse fraction. Coarse fraction from these sections contains abundant nodular type aggregates encrusting small forams. This period is marked by a high sedimentation rate comparable to Holocene. These parameters suggest that the productivity and precipitation have increased in the Holocene due to the intensification of the southwest monsoon. During the last glacial maximum and early deglacial period the high sedimentation rate indicates redeposition of the carbonates from the existing carbonate lithofacies situated between Quilon and Cape Comorin probably due to the slope instability.

Human Mesenchymal Stem Cells Isolated from Bone Marrow and Lymphoid Organs Support Tumor B-Cell Growth: Implications in Follicular Lymphoma Pathogenesis.

There is accumulating evidence that cellular microenvironment plays a key role in follicular lymphoma (FL) pathogenesis, both within tumor lymph nodes (LN) and in infiltrated bone marrow (BM) where ectopic LN-like reticular cells are integrated within malignant B-cell nodular aggregates. In normal secondary lymphoid organs, specific stromal cell subsets provide a highly specialized microenvironment that supports immune response. In particular, fibroblastic reticular cells (FRC) mediate immune cell migration, adhesion, and reciprocal interactions. The role of FRC and their postulated progenitors, i.e. bone marrow mesenchymal stem cells (MSC), in FL remains unexplored. In this study, we have investigated the relationships between FRC and MSC and their capacity to sustain malignant B-cell growth. Our findings strongly suggest that secondary lymphoid organs contain bona-fide MSC able to give rise at single-cell level to adipocytes, chondrocytes, and osteoblasts. These LN-derived MSC could also differentiate, in response to a combination of tumor necrosis factor-α (TNF) and lymphotoxin-α1β2 (LT), into fully functional FRC, able to construct a dense extracellular reticular meshwork positive for transglutaminase and fibronectin staining, to produce inflammatory (CXCL9, CXCL10, CCL5, CCL2) and LN-specific (CCL19) chemokines, and to favour lymphoma B-cell growth. Bone marrow-derived MSC (BM-MSC) acquire in vitro a complete FRC phenotype in the same culture conditions. As an exemple, BM-MSC had a strong, although not complete, protective effect on serum deprivation-induced apoptosis of BL2 cell line (mean percentage of CD20posCaspase-3pos cells: 24.8 +/− 17.5% in coculture with BM-MSC versus 80.7 +/- 10.4% in medium alone; P < .05; n =5) and pretreatment with TNF/LT fully restored BL2 viability (mean percentage of CD20posCaspase-3pos cells: 7.4 +/− 4.7%; P < .05; n = 5). Moreover, stimulation of stromal cells by TNF/LT before coculture enhanced the number of viable CD19pos primary FL B cells by 2.4-fold for BM-MSC and 2.3 fold for LN-MSC compared with the culture without stromal cells (P < .05; n = 6). Interestingly, cell contact with lymphoma B-cell lines or purified FL B cells trigger the differentiation of BM-MSC into FRC that, in turn, support malignant B-cell migration, adhesion and survival. Altogether, these new insights into the interactions between lymphoma cells and their microenvironment could offer original therapeutic strategies.

The Pathology of Devil Facial Tumor Disease (DFTD) in Tasmanian Devils (Sarcophilus harrisii)

A disfiguring and debilitating neoplastic condition known as devil facial tumor disease (DFTD) has been discovered in wild Tasmanian Devils (Sarcophilus harrisii) across 51% of its natural range, with population declines of up to 80% in some areas (C. Hawkins, personal communication). Between 2001 and 2004, 91 cases were examined. The tumors presented as large, solid, soft tissue masses usually with flattened, centrally ulcerated, and exudative surfaces. They were typically multicentric, appearing first in the oral, face, or neck regions. Histologically, the tumors were composed of circumscribed to infiltrative nodular aggregates of round to spindle-shaped cells, often within a pseudocapsule and divided into lobules by delicate fibrous septae. They were locally aggressive and metastasized in 65% of cases. There was minimal cytologic differentiation among the tumor cell population under light and electron microscopic examination. The results indicate DFTD to be an undifferentiated soft tissue neoplasm.

Traces of evaporites in Upper Cretaceous lacustrine deposits of Korea: Origin and paleoenvironmental implications

Diverse types of halite and sulfate evaporite traces occur in the Upper Cretaceous lacustrine deposits of the Jindong Formation and the Jangdong Tuff in Korea, in which dinosaur tracks are common. The halite traces usually occur as casts or moulds, and they include traces of primary halite hoppers, primary and intrasedimentary skeletal halite, and intrasedimentary tiny halite. The sulfate traces occur as intrasedimentary and displacive casts filled with sediments and sparry calcite, and the casts occur as diverse modes from single crystal casts through nodular aggregates to massive aggregates. Some aggregates of the sulfate casts are aligned in crack pattern, and selective occurrence of the laths in ripple troughs are observed. Soluble sulfate evaporite minerals such as gypsum, glauberite, or mirabilite are probable for the precursors of these traces. These halite and sulfate traces are interpreted to have been formed in a saline lake and mudflats. It is interpreted that meteoric water was responsible for the evaporite precipitation in the Jindong Lake and Jangdong Lake. Recycled brine produced by the repeated dissolution of evaporites might contribute to the evaporite precipitation in the paleo-Jindong Lake and the paleo-Jangdong Lake. The development of saline lake deposits in the Jindong Formation and the Jangdong Tuff suggests that the southern part of the Korean Peninsula remained an inland continental area during the Cretaceous resulting in semi-arid paleoclimatic condition due to an orographic effect by the location of the Korean Peninsula on continental margin in mid-latitude with topographic barriers during the Cretaceous. The occurrence of dinosaur tracks in the lake margin deposits of saline lake with frequent inflow of dilute meteoric water suggests that Upper Cretaceous dinosaurs inhabiting lakes on the Korean Peninsula might have drunken brackish water.

Mesenchymal stem cells cultured on a collagen scaffold: In vitro osteogenic differentiation

Objective Management of periodontal defects has always been a challenge in clinical periodontics. Recently mesenchymal stem cells (MSC) have been proposed for tissue regeneration in periodontal disease and repair of large bone defects. Bone regeneration has to be supported by a scaffold which has to be biocompatible, biodegradable, and able to support cell growth and differentiation. The aim of this study was to evaluate osteogenic differentiation of MSC seeded on a collagen scaffold. Design MSC were obtained from adult rat bone marrow, expanded and cultured in plastic dishes or seeded in a collagen scaffold (Gingistat ®). MSC were induced towards osteogenic differentiation using osteogenic supplements. Cell differentiation and calcium deposits were evaluated by immunoblotting, immunohistochemistry, histochemical techniques, enzymatic activity assay, and SEM–EDX analysis. Biomaterial in vitro degradation was evaluated by measuring mass reduction after incubation in culture medium. Results Rat MSC osteogenic differentiation was demonstrated by osteopontin and osteocalcin expression and an increase in alkaline phosphatase activity. MSC were distributed homogeneously in the collagen scaffold. Nodular aggregates and alizarin red stained calcium deposits were observed in MSC induced towards osteogenic differentiation cultured in dishes or seeded in the collagen scaffold. SEM–EDX analysis demonstrated that calcium co-localized with phosphorous. The biomaterial in vitro degraded in 4–5 weeks. Conclusions MSC from bone marrow differentiate towards osteogenic lineage, representing a suitable cell source for bone formation in periodontal regeneration. Gingistat ® collagen scaffold supports MSC distribution and differentiation, but its short degradation time may be a limitation for a future application in bone tissue regeneration.

Patterns of Stromal Invasion in Ovarian Serous Tumors of Low Malignant Potential (Borderline Tumors): A Reevaluation of the Concept of Stromal Microinvasion

Stromal-epithelial patterns of invasion in serous tumors of the ovary have been subclassified as destructive and nondestructive. By definition, well-differentiated serous tumors featuring destructive stromal invasion are classified as low-grade serous carcinomas whereas those with either no stromal invasion or stromal microinvasion are classified as serous tumors of low malignant potential (S-LMP). The histologic features of stromal microinvasion in ovarian S-LMP have been addressed in a variety of studies, but controversy persists regarding diagnostic criteria and prognostic significance, particularly in patients with high-stage disease. In addition, a subset of otherwise typical S-LMP has patterns of invasion that are not classic destructive invasion and do not meet the current diagnostic criteria for stromal microinvasion because of either qualitative features or size restrictions. To further evaluate the full histologic spectrum of stromal-epithelial patterns of invasion in otherwise typical S-LMP, we examined a series of 60 ovarian S-LMP (34 FIGO stage I; 26 FIGO stages II, III, and IV) with stromal-epithelial alterations not meeting criteria for classic destructive invasion. This group of cases included those meeting the definition of microinvasion and a subset that would be excluded based on size measurements or unusual qualitative features, but did not exhibit significant stromal reaction. Five patterns of invasion were identified: individual eosinophilic cells and cell clusters, cribriform, simple and noncomplex branching papillae, inverted macropapillae, and micropapillae. Individual, discrete aggregates of invasive epithelium ranged from 1 to 12 mm (mean, 1.4 mm) in greatest linear dimension as measured by conventional methods. The number of discrete foci ranged from 1 to greater than 10; in 7 tumors (12%), the invasive foci were diffusely scattered throughout the stroma without discrete aggregates. These stromal-epithelial alterations were associated with disease progression and/or death due to disease in 9 of 50 (18%) patients with follow-up (mean, 92.5 mo) and were covariant with other adverse prognostic features (invasive implants, nodular lymph node aggregates, high stage, and unresectable disease). Disease progression was most strongly linked to the presence of micropapillae, but the majority of patients with adverse outcome had the more common, classic stromal-epithelial patterns associated with microinvasion (ie, individual cells, cell clusters, and simple papillae). Neither size of the largest contiguous aggregate nor extent of stromal involvement correlated with outcome. Classic microinvasion disproportionately occurred in patients presenting during pregnancy (P<0.0001), and was not associated with adverse outcome in that setting, but follow-up was limited. Based on the cumulative outcome data, the presence of stromal-epithelial patterns of invasion distinct from classic destructive invasion in otherwise typical S-LMP stratifies patients at long-term risk for disease progression, but does not warrant a diagnosis of carcinoma or a change in current management schemes. Maintaining classification as a serous tumor of low malignant potential (serous borderline tumor) with stromal invasion seems appropriate even in the presence of diffuse stromal involvement or discrete aggregates measuring greater than 3 (or 5) mm. As the stromal-epithelial alteration featuring micropapillae may represent a comparatively higher-risk lesion with a clinical course analogous to that of low-grade serous carcinoma, pathologists should identify this specific stromal-epithelial pattern in the diagnostic report until sufficient data is acquired to form more definitive conclusions regarding its prognosis.

Uterine Adenomyoma

The aim of this study is to highlight the importance of diagnosing uterine adenomyoma and help in differentiating it from other sinister lesions. Adenomyoma of the uterus is a circumscribed nodular aggregate of benign endometrial glands surrounded by endometrial stroma with leiomyomatous smooth muscle bordering the endometrial stromal component. It may be located within the myometrium, or it may involve or originate in the endometrium and grow as a polyp. A retrospective analysis of 26 consecutive cases of uterine adenomyomas diagnosed in the Department of Pathology, Government Medical College, Chandigarh from January 1994 to December 2004 was done, and their clinical and histological features were analyzed. The criterion used for case identification was a circumscribed mass composed of benign endometrial glands with a stromal component consisting of endometrial type stroma surrounded by leiomyomatous smooth muscle. Mitotic figures were counted within 50 high-power fields (hpf) and recorded as the highest number per 10 hpf. The age of the patients ranged from 22 to 60 years (mean age, 41 years). The most common presenting symptom was abnormal vaginal bleeding (n = 15). Thirteen patients underwent panhysterectomy; 7, total hysterectomy; 1, subtotal hysterectomy; 4, polypectomy or tumor removal; and 1, curettage. Of the 26 cases of adenomyoma, 24 were in the corpus, 1 was in the cervix, and 1 was in the broad ligament. An associated leiomyoma was noted in 12 cases (46.9%). The adenomyomas were firm in consistency and, on cut section, showed a gray-white surface. Five tumors showed cystic spaces filled with dark brown material. On microscopic examination, the tumors were well demarcated from the surrounding structures. The endometrial glands were mostly tubular and showed relatively regular spacing from each other without any back-to-back arrangement. The glands were lined by benign proliferative pseudostratified columnar epithelium. An occasional typical mitotic figure was noted in these glands in a few cases. The glands were surrounded by endometrial stroma which was compact and spindly. This stroma was, in turn, bordered by leiomyomatous smooth muscle. Thick-walled blood vessels were commonly observed. One to two typical mitotic figures per 10 hpf were noted in the endometrial stroma in few cases; however, no mitosis was noted in the myometrial component. Associated adenomyosis was also noted in 8 cases (30.8%). Adenomyomas have to be distinguished from a number of other lesions, for example, adenomyosis, leiomyoma with entrapped glands, atypical polypoid adenomyoma, endometrial polyps, adenofibroma, and adenosarcoma. This study highlights the importance of correctly identifying this fairly common entity and helps to distinguish adenomyoma from other similar appearing benign and malignant lesions.

Lymph Node Involvement in Ovarian Serous Tumors of Low Malignant Potential (Borderline Tumors)

The occurrence of regional lymph node involvement (LNI) in patients with primary ovarian serous tumors of low malignant potential (S-LMP), although well described in the literature, continues to be problematic. Most studies indicate that LNI is not associated with an adverse prognosis, but there has not been a comprehensive study addressing the histologic patterns of LNI, the importance, if any, of classifying the type of LNI (ie, as either noninvasive or invasive in analogy to peritoneal implant classification), or the presence and significance of associated endosalpingiosis. To further evaluate LNI in S-LMP, 74 patients with ovarian S-LMP and a lymph node biopsy or sampling were studied. Thirty-one of 74 patients had LNI in pelvic (18; 58%), mesenteric/omental (9; 29%), paraaortic (8; 26%), or supradiaphragmatic (2; 6%) lymph nodes. The number of involved nodes ranged from 1 to 20 (mean, 11.1). Four patterns of LNI were identified: individual cells, clusters of cells, and simple, nonbranching papillae (28 of 31; 90%); intraglandular (21 of 31; 68%); cells with prominent cytoplasmic eosinophilia ("eosinophilic cell" pattern) (16 of 31; 52%); and micropapillary pattern (5 of 31; 16%). LNI was diffuse in at least one lymph node in 13 patients (42%) and formed nodular aggregates greater than 1 mm in 6 patients (19%). Nodal endosalpingiosis was present in 58% of cases with LNI compared with 35% without LNI (P=0.06). There was no significant difference in survival for patients with LNI compared with patients without LNI. However, the presence of discrete nodular aggregates of epithelium greater than 1 mm in linear dimension without intervening lymphoid tissue was associated with a statistically significant decreased disease-free survival when compared with other patterns of LNI (P=0.02). Nodular aggregates were strongly associated with desmoplastic fibrous stromal reaction (P=0.001) and micropapillary architecture (0.02). There was also a trend for decreased survival among patients with LNI without associated endosalpingiosis (56%) compared with patients with LNI associated with endosalpingiosis (85%) and those with endosalpingiosis only (93%). This study suggests that patients with ovarian S-LMP may be further substratified into risk categories by the presence of nodular aggregates of S-LMP in lymph nodes, a feature that is more common in cases with micropapillary architecture and associated stromal reaction in the intranodal tumor. This high risk pattern of LNI may have a predictive value similar to invasive peritoneal implants and deserves independent evaluation in future studies of S-LMP.

Case report of a Quilty lesion within a coronary artery

The Quilty lesion is the moniker of a lymphoid proliferation that resides predominantly in the endocardium and underlying myocardium within transplanted hearts. It has been described in the endocardium, myocardium, and epicardium. Although its pathogenesis is not understood, it is generally considered that the Quilty lesion is not a manifestation of acute rejection. However, its clinical significance and relation to acute rejection, such as its pathogenesis, are still not completely understood. Immunohistochemical studies distinguish between the cellular infiltrates of Quilty lesions and those associated with acute rejection. We describe, what we believe to be, the first case of a Quilty lesion in an epicardial coronary artery from an 8-year-old girl with congenital heart disease who required retransplantation 25 months after her cardiac transplantation for severe graft coronary artery disease. The lesion consisted of an intramural nodular aggregate of numerous T and B lymphocytes, with fewer macrophages, characteristic of a Quilty lesion.

Fatal HHV-8-Associated Hemophagocytic Syndrome in an HIV-Negative Immunocompetent Patient With Plasmablastic Variant of Multicentric Castleman Disease (Plasmablastic Microlymphoma)

Virus-associated hemophagocytic syndrome (VAHS) triggered by HHV-8 is extremely rare and has been reported only in 9 immunocompromised patients. We report the first case of HHV-8-associated VAHS in an HIV-negative, immunocompetent patient with plasmablastic variant (plasmablastic microlymphoma) of multicentric Castleman disease (MCD). This 61-year-old man presented with fever, cough, and bilateral inguinal lymphadenopathy. Biopsy of the right inguinal lymph node revealed plasmablastic MCD with nodular aggregates of plasmablasts expressing IgM, MUM1, HHV-8 latency-associated nuclear antigen, and viral interleukin-6. These plasmablasts were monotypic for Iglambda light chain expression but not Igkappa. All the B-cell clonality assays, including IgH-FR2, IgH-FR3, DH-JH, Igkappa, and Iglambda PCR, showed a polyclonal pattern. His serum human interleukin-6 level was markedly elevated and was negative for EBV acute infection/reactivation. The marrow aspirate showed florid hemophagocytosis. His disease progressed rapidly to multisystemic illness, and he died of acute respiratory failure in 1 month. Our case showed that HHV-8 might trigger VAHS in an immunocompetent patient with plasmablastic MCD. We speculated that our patient developed VAHS under the cytokine storm associated with the proliferating HHV-8-infected plasmablasts, similar to the EBV-triggered VAHS in patients with EBV-associated T-cell lymphoma.

Evolution of a True B-Cell Chronic Lymphocytic Leukaemia (B-CLL) in a Diffuse Immunocytoma after Treatment with Fludarabine.

In B-CLL CD5, CD23 antigen-experienced B-cell are the neoplastic population. However, a small proportion of patients may present a monoclonal component (MC) and lymphoplasmacytoid (LP) cells, different from those CD5,CD23 negative of immunocytoma. Fludarabine, a very effective drug in the treatment of B-CLL and indolent lymphomas, may favour opportunistic infections and secondary cancers due to intense and prolonged immunosuppression.Herein we report on a 58-year old woman with night sweats and weakness. Physical examination revealed small peripheral lymphoadenopathies. WBC were 17.2x109/l; the marrow was infiltrated by 52% small mature lymphocytes presenting a monotypic kappa light chain restriction and CD5, CD19, CD20, CD23, CD38, ZAP70 antigens. Cytogenetics revealed a normal karyotype, whereas FISH detected 13q- in 48% nuclei. A diagnosis of B-CLL in Rai stage IA without any MC was made. The patient did not receive any treatment and nine months later developed multiple adenopathies and a progressive splenomegaly. WBC were 32.9x109/l; the marrow was infiltrated by 78% mature B lymphocytes and 5% LP cells sharing the original phenotype. Therefore a progression in Rai stage III had occurred and the patient started treatment with oral fludarabine (40mg/m2/day for 5 days, repeated every 4 weeks) which was well tolerated. A clinical response was achieved after fourth courses, with disappearance of adenopathies and splenomegaly, and normalization of peripheral blood. Few days later the patient complained of itching. Her blood tests revealed eosinophilia (42%), but twenty days later an IgG kappa MC (4,3g/dl) became apparent. Ten days later the patient was admitted to our ward because of liver, spleen and lymphonode enlargement and a doubled MC (10.9g/dl). The bone marrow was infiltrated by 60% mature B lymphocytes with the original phenotype and 20% plasma cells with cytoplasmic IgM and IgG, a monotypic restriction for kappa light chains, CD38, CD138, CD56 antigens. FISH showed that both cell populations presented a 13q- and the analysis of the CDRIII region detected only one clonal cell population with mutated Ig(V) genes. In addition a lymphonode biopsy showed a parafollicular and nodular pattern of infiltration by CD20+, CD79a+, CD5+, CD23 +/−, CD10- and Bcl1- B-cells, showing a trend towards differentiation in secreting elements, and by 18% prolymphocytes and paraimmunoblasts grouped in nodular aggregates. In conclusion, the lymphonode histology addressed to an immunocytoma in initial evolution in Richter's syndrome.Our patient emphasizes the overlapping features between B-CLL and lymphoplasmacytoid lymphoma (LPL) since imunophenotypic, FISH, CDIII analysis demonstrated that the initial clonal cell population was able to undergo in vivo isotype switching to IgG, giving rise to LP elements and plasma cells producing high IgG levels. In addition, the correctness of the initial diagnosis is confirmed by the absence of t(9;14), a rearrangement typical of LPL, and the presence of 13q-, which prognostic impact in B-CLL with LP differentiation may be different than in typical B-CLL. The influence of fludarabine on the differentiation process remains unclear.

Neoplasm of hepatic stellate cells (spongiotic pericytoma): A new tumor entity in human liver

The purpose of this investigation was to classify a previously unknown tumor entity in human liver observed in a 35-year-old woman. It was characterized by an unusual accumulation of fusiform CD34-positive cells and was initially misconceived as a tumor of the liver sinusoids. The tissue was examined by light and electron microscopy and by immunocytochemical techniques with a broad spectrum of antibodies. The polycyclic tumor contained multiple nodular cell aggregates. The tumor cells possessed extensive cytoplasmic processes, rough endoplasmic reticulum, a prominent Golgi complex, and, in isolated cases, fat droplets. They expressed vimentin, CD34, CD105, CD99, CD56, and sm-actin. The matrix surrounding these cells was reactive for collagen types I, III and V, and fibronectin. The unusual aspect of this tumor is that it contained collections of cells that appeared to be hepatic stellate cells (Ito cells). It also contained hepatic cells arranged in plates, lobules, and capillarized sinuses. These findings suggest that the tumorous proliferation of hepatic stellate cells is functionally linked to the hepatocytes. It is unclear whether there is a link between the tumor and the patient's use of oral contraceptives. Referring to animal studies, different hepatocarcinogens may cause neoplastic Ito cell proliferation. The patient has remained recurrence-free during the 12 months since operation.