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We describe the case of a 67-year-old female patient presenting with constitutional symptoms and rapid decline. Two bone marrow core biopsies were performed, with spindled cells identified and thought to represent marrow involvement by systemic mastocytosis on the first biopsy. A diagnosis of metastatic vascular malignancy with sarcomatoid features was favored on the second core biopsy. The patient rapidly deteriorated and passed away. The post-mortem examination revealed a splenic angiosarcoma with metastasis to the liver and bone marrow. Splenic angiosarcoma is a rare, aggressive entity, with bone marrow metastasis even more uncommon. This report perceives this as a diagnostic consideration on bone marrow biopsies with spindled cells and explores the diagnostic dilemma and overlapping features of systemic mastocytosis and angiosarcoma.

Renal cell carcinoma (RCC) commonly metastasizes to areas such as the lungs, liver, bone, brain, adrenals, and lymph nodes. We present a rare case of a 59-year-old female patient with RCC metastasis to the gallbladder. The patient had undergone right nephrectomy for RCC more than 6 years prior to the metastasis. During routine follow-up, a polypoid lesion of the gallbladder was identified. Laparoscopic cholecystectomy was performed, and pathologic examination of the specimen revealed metastatic RCC. The patient was completely asymptomatic, which reinforces the importance of postoperative follow-up. Renal cell carcinoma is one of the few common malignancies for which there is good evidence of survival benefit from surgical resection of the metastatic tumours.

Extensive necrosis affecting more than 50% of the bone marrow is an extremely rare histopathological finding. Relatively little is known about its clinical significance because it is most commonly identified at autopsy - whether it is an independent prognostic marker or whether it is a surrogate marker of underlying disease burden remains unclear. We describe herein a case of a 66-year-old patient with acute myeloid leukemia who presented with acute bone marrow failure and was found to have extensive necrosis. We include presenting clinical features, pathology attained at biopsy, and the challenge of treatment. Bone marrow necrosis is a rare but important clinicopathological entity whose recognition may herald the way for more effective prognostication of underlying disease.

Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) is the most common subtype of marginal zone lymphoma (MZL), with stomach being the most frequent primary site, followed by salivary gland, lung and ocular adnexa. Although clinically indolent, MALT lymphoma has the potential of local recurrence and systemic spread. Amyloid deposition is a very unusual complication of MALT lymphoma. In this study, we report clinicopathologic features of 5 cases of MALT lymphomas with associated amyloid deposits. One case showed amyloid deposits in the primary lesion; the other four cases showed amyloid deposits only in recurrences. Previous studies suggest that the amyloid deposits do not implicate worse prognosis. In our study, although amyloid deposits were focal and organ confined, one patient had extensive deposits of amyloid in the large bowel wall leading to bowel perforation and another patient developed significant peripheral neuropathy due to amyloid deposits in the brachial plexus. In conclusion, amyloid deposits in MALT lymphomas are rare and organ/tumour confined. However, complications can be critical and cause considerable morbidity. Therefore, pathologists should be aware of the association between MALT lymphoma and amyloid deposition, and clinical follow up is warranted.

Case report: Primary intraocular lymphoma arose over a period of 9 months in the left eye of an 81-year-old woman who was blind in both eyes from temporal arteritis. During this period, she was treated with prednisone and methotrexate. Following a sudden total hyphema, the eye was enucleated. Examination revealed that, in addition to iris neovascularisation and central retinal artery occlusion, the neurosensory retina was replaced by atypical lymphocytes. Comments: Histological and immunohistochemical studies confirmed the presence of a lymphoma with features indicative of an immunosuppression-related disorder. The relationship of the lymphoma to the vascular changes within the eye is discussed.

Background. Posttransplant lymphoproliferative disorder (PTLD) remains a difficult management issue; therefore, many studies focus on the identification of risk factors to allow for preventive strategies. We investigated risk factors for PTLD in the adult renal transplant setting. Methods. A single-center, matched case-control study design was used. Cases were identified from patients who underwent a first renal transplant between January 1, 1985, and December 1, 2001. Two controls were chosen per case, matched (±1 year) by date of transplant and graft survival. Clinical and demographic data were ascertained from medical records. Pretransplant serology for Epstein-Barr virus (EBV) and cytomegalovirus was confirmed on frozen, stored sera. Statistical analysis included univariate and multivariable examination of putative risk factors using conditional logistic regression. Results. Twenty cases of PTLD were identified, an incidence of 2.4%. Median time from transplant to diagnosis was 55 months (range, 3-168 months), with 16 cases of late-onset PTLD ( > 1 year posttransplant). The only significant risk in univariate analysis was EBV-negative status at transplant (risk ratio 6.0, P=0.03). In multivariable analysis, EBV-negative status remained significant (adjusted risk ratio 8.9, P=0.01). The risk related to EBV status held true when late cases were analyzed separately (adjusted risk ratio 7.1, P=0.03). Conclusions. Pretransplant EBV-seronegative status is a strong risk for development of PTLD in adult renal allograft recipients, even in late disease. These results indicate that primary infection with EBV may have a pathogenic role in some cases of late PTLD.

Castleman's disease (CD), a disorder of lymphoid hyperplasia with an unknown etiology, is rare in children. It usually presents as a localized mass and is often cured by surgery. The authors report two unusual cases of CD in children. One patient had localized CD in the left supraclavicular region, a rare site of unicentric disease. She was ultimately treated by excisional biopsy, and the mass did not recur. Another patient presented with airway compression due to localized infiltrating mediastinal disease, not amenable to surgery. She refused prednisone and was treated with radiotherapy, with slow remission and no relapse for 4 years.

In this report, we describe a rare case of relapsed nodular sclerosing Hodgkin lymphoma presenting as a lesion of the oral mucosa. Although this is an uncommon clinical scenario, health care professionals should be aware of this possibility. A brief differential diagnosis and review of Hodgkin lymphoma is discussed.

We report a case of a 54-year-old previously healthy man with Hodgkin lymphoma who presented initially with a solitary cutaneous ulcer. Unlike non-Hodgkin lymphoma subtypes, skin involvement of Hodgkin lymphoma is extremely rare. Furthermore, the prognosis of Hodgkin lymphoma with skin infiltration is felt to be extremely poor. Contrary to other reports, this case demonstrates that a good response with standard therapy is possible.

Background: Akt is an ubiquitous signaling molecule that is associated with a wide array of biological effects including cell growth and proliferation. The dysregulation of Akt has been associated with cancer cell transformation, invasion and metastasis. While the roles of mutations in FGFR3, p53 and Ras have been the focus of the majority of studies of Transitional cell carcinoma (TCC) of the bladder, recent evidence suggests a link between the Akt pathway and the progression of TCC. Mutations in Akt pathway members have been identified in subsets of bladder TCCs, and Akt activation in TCC cell lines confers resistance to chemotherapeutics and promotes invasion in vitro. This led us to hypothesize that activated Akt may be an important biomarker in the progression of muscle invasive TCC. Methods: Tissue was obtained from 67 patients who had undergone radical cystectomy procedures for treatment of muscle invasive TCC. Tissue sections were taken from paraffin embedded samples and subjected to immunohistochemical analysis with anti Akt antibody to detect the activated form of Akt. A database of patient demographics, disease, treatment and survival parameters was generated and used to correlate 4, 12, 24 and 36 month disease-free intervals (DFI). Results: 53 of the 67 patients had sufficient follow-up to allow for DFI analysis. Of these 53 patients, 48 stained positively for pAkt, while 5 stained negatively. None of the pAkt negative patients had recurrent disease, while the pAkt negative patients suffered cumulative recurrence in 10, 19, 24, and 25 of the 48 patients at 4, 12, 24 and 36 months respectively. Chi square analysis reveals statistically significant differences in recurrence rates between pAkt negative and negative patients at 24 (p=0.0235) and 36 months (p=0.016). Tumor stage and nodal status were also strong predictors of recurrence. Conclusions: pAkt negative patients were found to have a significantly better prognosis for TCC recurrence, which indicates that pAkt status could be useful in helping to determine the prognosis for patients with muscle invasive TCC. These results lead us to speculate that the use of a serine threonine kinase inhibitor may prove to be therapeutically beneficial for TCC patients undergoing concurrent chemotherapy for their disease. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4187. doi:10.1158/1538-7445.AM2011-4187

Abstract 3112 Objective: To compare the utility of high sensitivity (5-colour) flow cytometry (FCM) vs. conventional cytology (CC) for detecting cerebrospinal fluid (CSF) involvement in patients with hematological lymphoid malignancies. Methods: The results of diagnostic evaluations on all CSF samples analyzed for involvement by neoplastic lymphoid cells between January 2005 and February 2010 were reviewed retrospectively. Cases were identified by reviewing logs of all FCM procedures performed during that time period. FCM was performed on the CSF using a 5-antibody panel (“high sensitivity”). Result: 108 patients (62M/46F) diagnosed with non-Hodgkin lymphoma or acute lymphoblastic leukemia underwent a total of 609 lumbar punctures (LP). The 359 samples that were sent for both CC and FCM form the basis of this analysis. The majority of the LP's (312/359, 87%) were negative for malignant cells by both FCM and CC (FCM-/CC-). 47 samples showed infiltration by tumor cells; of these, 25 (7%) were FCM+/CC+, and 22 (6%) were FCM+/CC-. No cases (0%) were FCM-/CC+. Using FCM as the gold standard, CC had a specificity of 100%, but a sensitivity of only 53%. Conclusion: High-sensitivity FCM has superior sensitivity to CC for diagnosing leptomeningeal involvement by lymphoid malignancies. CC failed to identify any additional cases that were not seen on FCM. This raises the question of whether performing CC on CSF samples to search for neoplastic lymphoid cells is of any additional diagnostic value. Disclosures: No relevant conflicts of interest to declare.

Background: Central nervous system (CNS) involvement by non-Hodgkin’s lymphoma (NHL) portends a very poor prognosis. There is no consensus in the literature on the “high- risk” features that predict for leptomeningeal disease, and no standardized clinical guidelines exist regarding CNS surveillance, prophylaxis or treatment for patients at increased risk. 2–4 colour flow cytometry (FCM) has been reported to be more sensitive than standard cytology in detecting occult leptomeningeal disease (Blood 2005,105:496). The current study evaluates the utility of a high-sensitivity (5-colour) flow cytometry technique for detecting occult lymphoma cells in the cerebrospinal fluid (CSF) of high-risk patients with NHL. Method: Patients with a new diagnosis of histologically aggressive B or T cell NHL were included in this study if they displayed one or more “high-risk” features for CNS involvement. Patients suspected of CNS relapse of NHL were also eligible for participation. Patients underwent routine staging investigations, with the addition of a diagnostic lumbar puncture (LP) during initial assessment. CSF was tested by standard cytology, cell count and biochemistry, and an additional 5 ml was obtained for analysis by high-sensitivity FCM on a Beckman Coulter FC500. The antibody panel (5 antibodies per tube) was customized according to the phenotype of the lymphoma. The key markers for B cell lymphoma were CD19/kappa/lambda with CD5 or CD10. CD45 was used to identify all white blood cells in the sample. Results: Seventeen patients (8M/9F) with a median age of 59 (range 36–85) have been tested. Patients displayed anywhere from 2–6 “high-risk” features for CNS involvement. These included: HIV positivity (2), primary mediastinal B-cell lymphoma (4), bone marrow (5), multifocal bone (2), paraspinal (1), nasopharyngeal (2) or orbital (1) involvement, elevated serum LDH (12), multiple extranodal sites of disease (5), poor performance status (2), high IPI (3), B-symptoms (9), stage IV disease (11), and otherwise unexplained neurological symptoms (3). 14 patients underwent CSF analysis at time of initial diagnosis, one of whom had cranial nerve palsies secondary to a nasopharyngeal mass extending to the skull base. The other 3 were tested at relapse, transformation, and suspected CNS relapse ultimately diagnosed as a stroke. Despite the presence of these features, CSF analysis was negative for lymphoma cells by both cytology and FCM in all but one of the patients tested. However this patient had very high numbers of circulating lymphoma cells in the peripheral blood (PB), and the positive result was felt to be due to PB contamination of the CSF during a “bloody tap.” One patient with vague neurological symptoms had a negative LP at diagnosis, and later developed frank CNS involvement by lymphoma, but was too unwell to undergo a repeat LP. Conclusions: Given the limited number of patients enrolled thus far and the low prevalence of patients with NHL and CNS involvement (2/17), it is difficult to fully assess the utility of high-sensitivity FCM in the diagnosis of occult leptomeningeal disease. It is of interest that CSF analysis was negative even in the patient with cranial nerve palsies and in the patient who later developed multiple CNS lesions secondary to lymphoma, suggesting that this technique may have limited sensitivity in diagnosing leptomeningeal disease. The systematic screening of high-risk patients cannot yet be recommended as standard clinical practice.