Undiagnosed Metastatic Breast Carcinoma Presenting as Thrombotic Thrombocytopenic Purpura.

Cancer-associated thrombotic microangiopathy has a documented relationship with metastatic disease. Other examples of thrombotic microangiopathy (TMA) include thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS). All these conditions can present with microangiopathic hemolytic anemia as well as thrombocytopenia. However, when these findings occur in association with cancer, they often carry a poor prognosis. Though associated with metastasis, microangiopathic hemolytic anemia, and thrombocytopenia have rarely been seen as the presenting signs of malignancy. We present the case of a 66-year-old female with no known history of cancer who exhibited an intriguing clinical presentation, including progressive dyspnea worsening with exertion, diarrhea, and dizziness. Laboratory investigations revealed Coombs-negative hemolytic anemia with schistocytes on blood smears and thrombocytopenia. The patient's condition raised concerns for TTP, prompting the initiation of plasmapheresis. However, despite treatment, the anemia and thrombocytopenia showed no improvement, leading to further investigations. Ultimately, a bone marrow biopsy revealed tumor cells arranged in nests and single files, leading to a diagnosis of metastatic carcinoma, consistent with breast primary. This was the patient's first known sign of breast cancer. This case emphasizes the significance of considering metastatic cancer as a potential differential diagnosis in patients presenting with similar signs and symptoms.

Concurrent Splenic Marginal Zone B Cell Lymphoma and Metastatic Pancreatic Adenocarcinoma Diagnosed on Splenectomy for Suspected Splenic Abscess.

Splenic marginal zone lymphoma (SMZL) is an uncommon low-grade B-cell lymphoma. It is an indolent lymphoma with a median survival rate of greater than 10 years. Most patients are asymptomatic, but some patients may present with upper abdominal pain and distention, while others may present with splenomegaly, emaciation, fatigue, or weight loss. Due to the long median survival, patients with SMZL may develop a second primary malignancy. Pancreatic adenocarcinoma is the most common malignant neoplasm of the pancreas. It has a poor prognosis with a five-year survival rate of 10%. Fifty percent of patients have metastatic disease on presentation. However, the spleen is not a common site of metastasis for malignant tumors from other primary sites including the pancreas. Here we present a case of a 78-year-old African American patient, who was found to have previously undiagnosed, concurrent metastatic pancreatic adenocarcinoma and SMZL diagnosed on splenectomy for a suspected splenic abscess.

Cotyledonoid Dissecting Leiomyoma: A Rare Variant of Leiomyoma of the Uterus.

Cotyledonoid dissecting leiomyoma is a rare variant of leiomyoma and has only been reported a few times in the literature. As a result of its alarming gross and radiologic appearance, it must be differentiated from other malignant smooth muscle tumors. We report a case of cotyledonoid dissecting leiomyoma in an African American premenopausal woman with a medical history of anemia, abnormal uterine bleeding, and a cervical mass. A total hysterectomy was performed on the patient. On pathological examination, the gross and microscopic appearance of the tumor was consistent with that described in previous reports of cotyledonoid dissecting leiomyoma. However, our case showed focal areas of increased mitotic activity with 5 mitoses per high power field but no tumor cell necrosis or cellular atypia. This tumor does not have malignant potential, but clinicians and pathologists must be aware of its existence to avoid overtreating patients.

Multiple Primary Malignant Neoplasms in African Americans: A Case Series and Literature Review.

Multiple primary malignant neoplasms (MPMNs) or multiple primary malignancies are defined as two or more histologically distinct malignancies present in the same individual. While second or higher-order malignancies account for approximately 18% of all cancers in the United States, it is reasonable to presume that MPMNs are now occurring more frequently than previously reported. Underserved groups such as blacks and Hispanics may represent a high proportion of these underreported cases due to well-established health disparities. Although the role of health disparities has been well established in single primary malignancies, less is known on racial differences in patients with multiple primaries. In comparing MPMNs by race, blacks have lower survival rates compared to white patients. Moreover, despite the lower overall incidence of MPMNs in blacks compared to white patients, when broken down by the specific types of cancers and gender, there are significant racial disparities in the incidence of prostate cancer and possibly other cancers. Further research and case reports are required to explore the risk factors of developing MPMNs in these groups. Our case series explores three African American patients with MPMNs that are rarely described in the literature and outlines the management challenges of treating multiple malignancies.

A Case of Classical Hodgkin's Lymphoma Presenting With Intractable Pruritus.

Hodgkin's Lymphoma presenting with hypereosinophilia and intractable pruritus is a rare entity. Diagnostic and therapeutic decisions remain a challenge in such patients. Here we report a case of a 25-year-old female with a special case of Hodgkin's lymphoma. A 25-year-old was admitted to our hospital for intractable pruritus and was found to have significant leukocytosis with eosinophilic predominance. The patient underwent a bone marrow biopsy and mediastinal lymph node biopsy, which confirmed classical Hodgkin's lymphoma. Furthermore, the patient was given six cycles of adriamycin, bleomycin, vincristine, and doxorubicin (ABVD) chemotherapy and initially showed improvement; however, she relapsed within a short period. Post-treatment positron emission tomography (PET) scan showed interval progression of the disease, and so the patient was referred for a clinical trial with immunotherapy and Brentuximab vedotin.

Plasma Cell Leukemia Presenting as a Chest Wall Mass: A Case Report.

Plasma cell leukemia (PCL) is an uncommon neoplasm of plasma cells, with an aggressive clinical course and poor outcome, even with current standard of care. It can occur either de novo (primary PCL) or as a progression of multiple myeloma (MM). This disease has unique diagnostic criteria but certain genetic markers and clinical features may overlap with MM. Due to the low prevalence of PCL, guidelines on its management are extrapolated from the management of MM and based on small retrospective studies and cases reports/series. We present an interesting case of PCL in a middle-aged African-American male, who was diagnosed incidentally after chest wall imaging for an unrelated complaint. The diagnostic approach, management and outcomes of PCL are discussed.

ALK-positive large B-cell lymphomas express a terminal B-cell differentiation program and activated STAT3 but lack MYC rearrangements.

ALK-positive large B-cell lymphoma is an aggressive lymphoid neoplasm characterized by a monomorphic proliferation of immunoblast-like cells expressing a plasmablastic phenotype and carrying ALK rearrangements. MYC rearrangements are frequent in plasmablastic lymphomas, advanced plasma cell myelomas and a subgroup of diffuse large B-cell lymphomas, but their presence in ALK-positive large B-cell lymphomas is unknown. MYC expression is downregulated by BLIMP1, a master modulator of plasma cell differentiation. BLIMP1 and MYC are upregulated by STAT3, a signal transducer activated by ALK. To determine the role of BLIMP1, MYC and STAT3 in the pathogenesis of ALK-positive large B-cell lymphomas, we investigated MYC rearrangement and the expression of MYC, phosphorylated STAT3, BLIMP1, PAX5 and XBP1 in 12 ALK-positive large B-cell lymphomas. All cases expressed ALK with a granular cytoplasmic pattern. Nine cases had a split signal consistent with an ALK rearrangement. Three additional cases showed a deletion of the 5' or 3' end of the ALK probe consistent with cryptic translocation. PAX5 was virtually negative in all cases tested, whereas BLIMP1 was expressed in all tumors and XBP1 in 11 of 12. Phosphorylated STAT3 was observed in all cases with a strong and diffuse nuclear pattern. MYC rearrangements were not identified in any tumor, but MYC gains and amplification were detected in six cases and one case, respectively. MYC protein was expressed in all tumors independently of MYC gene alterations. These results indicate that ALK-positive large B-cell lymphomas express a complete plasmablastic differentiation program but, contrary to plasmablastic lymphomas, do not have MYC rearrangements. STAT3 is constantly activated and may be an alternative mechanism to promote MYC expression in these tumors. The relevance of the ALK/STAT3 pathway in the pathogenesis of ALK-positive large B-cell lymphomas may offer an attractive target for new therapies.

IG/MYC rearrangements are the main cytogenetic alteration in plasmablastic lymphomas.

Plasmablastic lymphoma (PBL) is an aggressive lymphoma characterized by a terminally differentiated B-cell phenotype that usually occurs in the immunocompromised or elderly patients. Although the clinical and pathologic characteristics of these tumors have been defined, the genetic alterations involved in their pathogenesis are not well known. In this study, we have investigated the chromosomal alterations of MYC, BCL2, BCL6, MALT1, PAX5, and IGH loci using fluorescence in situ hybridization in 42 PBL and 3 extracavitary primary effusion lymphomas. MYC rearrangements were identified in 20 of 41 (49%) PBL and the immunoglobulin (IG) genes were the partners in most tumors. MYC rearrangements were more common in Epstein-Barr virus (EBV)-positive (14 of 19, 74%) than EBV-negative (9 of 21, 43%) tumors (P<0.05). No rearrangements of BCL2, BCL6, MALT1, or PAX5 were detected in any PBL but gains of these loci were observed in 31% to 41% of the cases examined. Twelve of the 40 PBL in which 3 or more loci could be investigated had multiple simultaneous gains in 3 or more loci. No differences in the survival of the patients according to MYC were observed but the 4 patients with the longest survival (>50 mo) had no or low number of gains (<3). No rearrangements of any of these loci were seen in the primary effusion lymphomas. In conclusion, PBL are genetically characterized by frequent IG/MYC translocations and gains in multiple chromosomal loci. The oncogenic activation of MYC in these lymphomas may be an important pathogenetic element associated with EBV infection.

Plasmablastic lymphoma with MYC translocation: evidence for a common pathway in the generation of plasmablastic features.

Plasmablastic lymphoma, which is considered a subtype of diffuse large B-cell lymphoma, shares many similar morphological and immunophenotypic features with plasmablastic transformation of plasma cell myeloma. In the setting of human immunodeficiency virus (HIV) infection, both types of neoplasms can be associated with Epstein-Barr virus (EBV), thus making their distinction challenging. Moreover, the biological relationship between these entities remains unclear. We report four unique cases of plasmablastic lymphoma occurring in the setting of HIV infection that had overlapping clinical and genetic features with plasma cell myeloma. We reviewed the clinical, morphological, and cytogenetic findings and performed immunohistochemistry, in situ hybridization for EBV, chromosome analysis, and fluorescent in situ hybridization (FISH) using the MYC break-apart rearrangement probe. All patients were males with a median age of 45 years. In addition to extra-nodal disease, plasmablastic morphology, and phenotype typical of plasmablastic lymphoma, three of the four cases also showed clinical findings overlapping with plasma cell myeloma, that is, monoclonal serum immunoglobulin and lytic bone lesions. Furthermore, these cases showed complex cytogenetic changes that are more commonly observed in plasma cell myeloma. A unique feature was the presence of MYC (8q24.1) rearrangement confirmed by FISH in all four cases. MYC translocation has been associated with tumor progression in multiple myeloma but has only rarely been previously reported in plasmablastic lymphoma. These cases show a clinical and biological relationship between plasmablastic lymphoma and the plasmablastic variant of plasma cell myeloma. Dysregulation of MYC may be a common genetic mechanism that imparts plasmablastic morphology and aggressive clinical course to B-cell neoplasms at a later stage of differentiation.

Case of chronic eosinophilic leukemia with deletion of chromosome 16 and hepatitis C.

Chronic eosinophilic leukemia is a rare entity, characterized by eosinophilia of >1.5 x 10(9)/L, persisting for >6 months after exclusion of other reactive and neoplastic causes of eosinophilia, and occurring in association with a clonal cytogenetic abnormality. Various chromosomal abnormalities have been associated with chronic eosinophilic leukemia. Partial deletion of the long arm of chromosome 16 is a cytogenetic abnormality first reported 20 years ago in patients with acute myeloid leukemia associated with bone marrow eosinophilia (AML-M4Eo). We report a case of a 45-year-old African-American male with hepatitis C and sustained peripheral blood eosinophilia who presented with gross hematuria, dyspnea on exertion, chills, decreased appetite and weight loss of 40 pounds associated with hepatosplenomegaly and lymphadenopathy. Bone marrow biopsy showed clonal cytogenetic abnormality consisting of deletion of the long arm of chromosome 16 (16q22). Philadelphia chromosome t (9;22) and polymerase chain reaction (PCR) analysis for C-kit and platelet-derived growth factor receptor-alpha (PDGFRA) mutations were negative. The patient was treated with imatinib at 400 mg/d with improvement of symptoms, reduction of lymphadenopathy and normalization of the eosinophil count. To our knowledge, this is the first case report of isolated del (16) (q22), a cytogenetic abnormality associated with AML-M4Eo, occurring in chronic eosinophilic leukemia. Whether this cytogenetic abnormality might represent a prodromal phase of AML-M4Eo is not known. In addition, the role of hepatitis C in inducing clonal proliferation of eosinophils is unclear.

Marginal zone B-cell lymphoma in children and young adults.

We describe the clinicopathologic findings of 48 cases of marginal zone B-cell lymphoma (MZL) in children and young adults, a disease that has been recognized previously only rarely in this age group. Patients ranged in age from 2 to 29 years, with pediatric patients (< or =18 years) comprising 52% of the cases. As in adults, both primary nodal (N) and extranodal (E) MZL were observed. However, primary NMZL comprised the majority of the cases (67%) and demonstrated distinctive clinical and histologic features. NMZL occurred most commonly in young males (median 16 years, male/female ratio 5.4:1), with no underlying disease, presenting as localized adenopathy (90% stage I), with excellent prognosis and low rate of recurrence. In contrast, EMZL were much less common, and patients were older (median 24.5 years), with only a slight male predominance (male/female ratio 1.2:1). Most patients had localized disease (73% stage I) with excellent prognosis and infrequent recurrences. In addition, an association with autoimmune disease was observed in 19% of the EMZL. Both primary NMZL and EMZL in young patients shared similar morphologic and immunophenotypic findings to those described in adults and were monoclonal B-cell proliferations with monoclonality demonstrated in 94% of the cases. A common morphologic feature in NMZL was disruption of residual follicles resembling progressive transformation of germinal centers (PTGC), observed in 66% of the cases. Although the precise relationship of primary NMZL and the PTGC-like changes is unclear, it is possible that NMZL arises in a background of PTGC, as florid PTGC often occurs in young males. We conclude that EMZL in children and young adults are similar to EMZL of mucosa-associated lymphoma tissue occurring in older patients. However, pediatric NMZL appear to have distinctive clinical and histologic features.

Florid CD4+, CD56+ T-cell infiltrate associated with Herpes simplex infection simulating nasal NK-/T-cell lymphoma.

We report a case of Herpes simplex virus (HSV) infection of the nasopharynx associated with a dense CD4+, CD56+ T-cell infiltrate that simulated lymphoma on clinical, histologic, and immunophenotypic grounds. Histologic examination showed a tumorlike lymphoid infiltrate with extensive necrosis. Multinucleated giant cells with "ground-glass" nuclei characteristic of HSV were observed in necrotic areas but were not prominent. Immunohistochemical studies of the lymphoid infiltrate revealed a predominance of T cells, positive for CD3, CD4, CD5, and CD56. Immunohistochemical staining with HSV antibody was focally positive in the multinucleated giant cells. Molecular studies using PCR and Southern blot were positive for HSV Type II. PCR studies for T-cell receptor gamma and immunoglobulin heavy chain gene rearrangements showed no evidence of a clonal population. In situ hybridization studies for Epstein-Barr virus (EBV) were negative. The clinical presentation of a large fungating mass, the extent of the lymphoid infiltrate, and the expression of CD56 all raised the possibility of a nasal NK/T cell lymphoma. However, the presence of HSV, lack of angioinvasion and angiodestruction, absence of EBV, and polyclonal T-cell nature of the infiltrate argued against this diagnosis. Although prior studies have not fully characterized the immunophenotypic features of the lymphocyte response to HSV in infected tissues, we postulate that the CD56+, CD4+ T-cell reaction represents a florid antiviral immune response.