The clinical spectrum of Castleman's disease.

Castleman's disease (CD) is a rare, poorly understood lymphoproliferative disease. The spectrum of symptoms and course of disease are broad, but there is no large study describing the natural history of this disease. Basic clinic and laboratory data from the records of 113 patients with CD evaluated at the Mayo Clinic and University of Nebraska were abstracted. The impact of these variables on overall survival (OS) from time of diagnosis was evaluated. Sixty patients had multicentric disease. Of the patients with multicentric CD, 32% had criteria sufficient for a diagnosis of POEMS syndrome. For all patients, 2, 5, and 10-year OS was 92%, 76%, 59%, respectively. Most of the factors identified as risk factors for death on univariate analysis cosegregated with diagnostic criteria for POEMS syndrome, which supported the concept of four categories of CD, which are (along with their 5-year OS): (1) unicentric CD (91%); (2) multicentric CD associated with the osteosclerotic variant of POEMS syndrome (90%); (3); multicentric CD without POEMS syndrome (65%); and (4) multicentric CD with POEMS syndrome without osteosclerotic lesions (27%). We have demonstrated that CD represents a spectrum of disease that can be differentiated by simple prognostic factors that provide a framework for further study.

A Previously Unrecognized Granulomatous Variant of Gamma-Delta T-Cell Lymphoma.

Primary cutaneous γδ T-cell lymphoma (PCGD-TCL) is an extremely rare and aggressive T-cell neoplasm with complex heterogeneity. We present a series of two patients who presented with firm, subcutaneous nodules and were diagnosed with PCGD-TCL. In both cases, biopsies demonstrated a both superficial and deep adnexotropic infiltrate comprised of angiocentric, medium- to large-sized atypical lymphocytes. The infiltrate extended into the panniculus. Immuno-histochemical stains highlighted atypical lymphocytes that expressed CD3, CD8 and CD56 but were negative for EBV ISH. A brisk histiocytic response with focal aggregation into granulomas was highlighted with a PG-M1 stain. The atypical lymphocytes were positive for gene rearrangements on a TCR delta stain and negative for ßF-1. CT and PET scan in one of the two patients demonstrated diffuse, subcutaneous, ground-glass foci; hypermetabolic soft tissue nodules; and lymphadenopathy in the lungs, as well as splenomegaly. A diagnosis of histiocyte-rich PCGD-TCL was rendered. A histiocyte-rich, granulomatous variant of γδ T-cell lymphoma is extremely rare. Its potentially misleading resemblance to inflammatory granulomatous conditions could pose a diagnostic pitfall in this already challenging condition. This variant may resemble granulomatous mycosis fungoides and granulomatous slack skin syndrome, but it has a distinct, aggressive clinical outcome.

Primary peritoneal myeloid sarcoma in association with CBFB/MYH11 fusion.

Myeloid sarcoma, also known as chloroma or granulocytic sarcoma is an extramedullary disease process that typically presents in association with acute myeloid leukemia during initial presentation or at relapse. Often associated with cytogenetic mutations, including t(8;21)(q22;q22); RUNX1/RUNX1T1, and less frequently with inv(16)(p13.1q22) or t(16;16)(p13.1;q22); CBFB/MYH11, myeloid sarcoma is most commonly discovered in skin, soft tissue, bone, and connective tissue. In rare circumstances, myeloid sarcoma can present without any evidence of bone marrow or leukemic involvement. These cases of de novo myeloid sarcoma are rare, and are commonly misdiagnosed due to similarities with other entities. We report an unusual case of a primary de novo peritoneal myeloid sarcoma, in association with inv(16)(p13;q22) and clonal heterogeneity at different sites of involvement, that has responded well to AML induction therapy and consolidation treatment with gemtuzumab ozogamicin and high dose cytarabine. Cytogenetics, immunophenotyping, and chromosomal analysis, were each critical in establishing a proper diagnosis as well as helping to develop appropriate therapeutic strategies for this rare entity.

Primary age-related EBV-associated effusion-based lymphoma successfully treated with rituximab and thoracentesis.

EBV-positive HHV8-negative EBL is part of the spectrum of EBV-positive diffuse large B-cell lymphoma NOS. This entity can be labeled as primary age-related EBV-associated EBL and appears to respond well to rituximab and thoracentesis.

Outcomes of Hepatosplenic T-Cell Lymphoma: The Mayo Clinic Experience.

BACKGROUND: Hepatosplenic T-cell lymphoma (HSTCL) is a rare subtype of peripheral T-cell lymphoma accounting for less than 1% of non-Hodgkin lymphomas. It is generally associated with poor prognosis. PATIENTS AND METHODS: We performed a cohort study of patients with HSTCL treated at the Mayo Clinic between 1996 and 2020 exploring the clinical characteristics and therapeutic outcomes. RESULTS: Twenty-two cases of HSTCL were identified with a median (range) age at diagnosis of 45.5 (15.5-80.6) years and a male predominance (15/22, 68.2%). Clinical characteristics include massive splenomegaly in 16 patients (73%), hepatic involvement in 13 (59%), and chronic immunosuppressed state in 8 (36%). Phenotypically, lymphoma cells had gamma/delta T-cell receptor expression in 18 (82%) and alpha/beta in 4 patients. Cytogenetic abnormalities included isochromosome 7q (i7q) in 8 (62%) of 13 and trisomy 8 in 4 (44%) of 9. The median (range) follow-up of surviving patients was 33 (2.5-137) months. The median progression-free and overall survival were 9.5 months (95% CI, 1.8, 16.3) and 12.4 months (95% CI, 4.9, 18.5), respectively. Long-term survival was seen in 4 (18%) of 22 patients, with survival of 55, 74, 95, and 137 months. Moreover, 3 of 4 long-term survivors had splenectomy as part of initial treatment, and 2 of 4 long-term survivors received an allogeneic hematopoietic cell transplant (allo-HCT). CONCLUSION: Liver involvement and chronic immunosuppression were associated with shorter survival. Although splenectomy and allo-HCT have anecdotal benefit in the literature, our data do not show a statistically significant benefit of splenectomy and/or allo-HCT, likely as a result of our small sample size.

Radiation-induced pseudotumor following therapy for soft tissue sarcoma.

PURPOSE: The purpose of this study was to describe the prevalence and imaging appearance of radiation induced pseudotumors in patients following radiation therapy for extremity soft tissue sarcomas. MATERIALS AND METHODS: We retrospectively reviewed the serial magnetic resonance (MR) images of 24 patients following radiation therapy for extremity soft tissue sarcomas. A total of 208 exams were reviewed (mean, 8.7 exams per patient) and included all available studies following the start of radiation therapy. Exams were analyzed for the identification of focal signal abnormalities within the surgical bed suggesting local tumor recurrence. Histopathologic correlation was available in nine patients suspected of having local tumor recurrence. Additional information recorded included patient demographics, tumor type and location, radiation type, and dose. RESULTS: The study group consisted of 12 men and 12 women, having an average age of 63 years (range, 39-88 years). Primary tumors were malignant fibrous histiocytoma (n = 13), leiomyosarcoma (n = 6), liposarcoma (n = 3), synovial sarcoma (n = 1), and extraskeletal chondrosarcoma (n = 1). All lesions were high-grade sarcomas, except for two myxoid liposarcomas. Average patient radiation dose was 5,658 cGy (range, 4,500-8,040 cGy). Average follow-up time was 63 months (range, 3-204 months). Focal signal abnormalities suggesting local recurrence were seen in nine (38%) patients. Three of the nine patients with these signal abnormalities were surgically proven to have radiation-induced pseudotumor. The pseudotumors developed between 11 and 61 months following the initiation of radiation therapy (mean, 38 months), with an average radiation dose of 5,527 cGy (range, 5,040-6,500 cGy). MR imaging demonstrated a relatively ill-defined ovoid focus of abnormal signal and intense heterogeneous enhancement with little or no associated mass effect. CONCLUSION: MR imaging of radiation-induced pseudotumor typically demonstrates a relatively ill-defined ovoid mass-like focus of intense heterogeneous enhancement with little or no associated mass effect. Imaging follow-up or biopsy may be an alternative course of action to surgical re-exploration if this diagnosis is considered. The study revealed radiation-induced pseudotumor in 12.5% of patients in our extremity study group, suggesting that radiation-induced pseudotumor may be more prevalent than previously reported.

Adenocarcinoma developing at an ileostomy: report of a case and review of the literature.

Primary adenocarcinoma of a permanent ileostomy is a rare and unusual complication. We report a case of primary adenocarcinoma arising at an ileostomy site 46 years after total proctocolectomy for Crohn's colitis. In addition, we performed a literature search and found 36 such cases reported. Based on the results of this case and literature review, we concur with the previously reported theory that the etiology of this phenomenon is likely the result of colonic metaplasia in the ileal mucosa, which eventually progresses to carcinoma. Common presenting symptoms include a bleeding, friable mass, difficulty fitting the stomal appliance, and bowel obstruction. Once confirmed by biopsy, appropriate surgical en bloc excision and stomal relocation is the mainstay of therapy. Lymph node metastasis occurs in 19 percent of patients and survival is at least 85 percent. Adjuvant therapy may be of additional benefit. Patient education is important for early detection as the lesion typically appears an average of 27 years after the original operation.

Primary alveolar soft-part sarcoma of the liver: anomalous presentation of a rare disease.

Alveolar soft-part sarcoma is a highly vascular soft-tissue tumor that is uniformly malignant. It comprises less than 1 per cent of all soft-tissue sarcomas. Patients with alveolar soft-part sarcoma most frequently are aged 15 to 35 years, and the soft tissues of the lower extremities typically are affected. In the pediatric population, it most frequently occurs in the head and neck and particularly affects the tongue and orbit. Alveolar soft-part sarcoma has been described as a primary lesion in the trunk, upper extremities, and retroperitoneum; more novel locations include the mediastinum, female genital tract, stomach, bone, and larynx. Numerous case reports describe alveolar soft-part sarcoma in diverse anatomic locations, but this report is, to our knowledge, the first documentation of primary alveolar soft-part sarcoma of the liver. We describe a 47-year-old woman with such a manifestation. Despite surgical resection and numerous chemotherapeutic regimens, this patient had widespread metastasis and died approximately 2 years after the diagnosis was established.

Myelodysplasia-related acute myeloid leukemia and acute promyelocytic leukemia: concomitant occurrence of two molecularly distinct diseases.

Concurrent presentation of acute promyelocytic leukemia (APL) with other hematologic diseases in the absence of previous chemotherapy or ionizing radiotherapy treatment is very rare. We present a case of simultaneous occurrence of APL with myelodysplastic syndrome (MDS)-related acute myeloid leukemia (AML). A 43-yearold female presented with 3 month of history fatigue, night sweats, chills and pancytopenia. Bone marrow aspirate and biopsy demonstrated 20% myeloid blasts with dysplastic changes admixed with abnormal promyelocytes. Cytogenetic analysis showed tetraploidy and deletion in chromosomes 5q and 7q and polymerase chain reaction showed presence of PML/RARA mRNA transcripts, confirming the presence of concurrent APL and MDS-related AML. Induction chemotherapy with cytarabine and daunorubicin was initiated along with all-trans retinoic acid. This is the first case to be reported in the literature of concurrent occurrence of APL with MDS-related AML. Treatment with 7 + 3 regimen and ATRA was successful in inducing complete remission.

Colorectal lymphangioma.

Lymphangiomas of the colon are historically rare benign tumors. Only 331 cases have been reported in the world medical literature between 1931 and 2004. With widespread use of colonoscopy, however, they are being found more frequently. We report the case of a 74-year-old woman in whom a colonoscopy revealed a 3 x 4-cm submucosal lesion in the cecum that was eventually diagnosed as a lymphangioma. A CT of the abdomen showed a soft-tissue mass in the cecum and a low-density hepatic lesion. An endoscopic ultrasound of the colon showed a 3 x 4-cm hypoechoic lesion with internal septa arising from the submucosal layer of the cecum. This lesion resembled a vascular malformation; therefore a biopsy specimen was not taken. Pathologic findings of a specimen taken after a subsequent right hemicolectomy identified a submucosal lymphangioma. Published reports indicate that colonoscopy cures most lesions smaller than 2.5 cm in diameter. Resection should be reserved for larger lesions or those in patients exhibiting protein-losing enteropathy.

Mantle cell lymphoma with a novel t(11;12)(q13;p11.2): a proposed alternative mechanism of CCND1 up-regulation.

Mantle cell lymphoma (MCL) is typically characterized by t(11;14), which places the IGH@ enhancer elements upstream of CCND1. This fusion results in up-regulation of CCND1 and consequently its protein product cyclin D1. Recent studies have shown that in MCL, mutations or translocations occurring within the 3' untranslated region (UTR) of the CCND1 gene can result in a truncated mRNA transcript that is more stable and associated with more aggressive disease. We identified a case of MCL showing cyclin D1 overexpression by immunohistochemistry and a t(11;12)(q13;p11.2) by conventional cytogenetic studies. Next-generation genomic sequencing indicated a chromosomal break through the CCND1 3'-UTR and fusion with a non-coding region of chromosome 12. We suggest that, in the absence of the typical CCND1/IGH@ fusion, this rearrangement promotes MCL pathogenesis by eliminating miRNA interaction elements within the 3'-UTR of the CCND1 mRNA transcript consequently resulting in CCND1 overexpression.

Comprehensive Genomic Profiling of a Rare Thyroid Follicular Dendritic Cell Sarcoma.

We previously reported an extremely rare case of follicular dendritic cell sarcoma (FDCS) presented as a thyroid mass. Given the rarity of this disease, there are no personalized and molecularly targeted treatment options due to the lack of knowledge in the genomic makeup of the tumor. A 44-year-old white woman was diagnosed with an extranodal FDCS in thyroid. The patient underwent a total thyroidectomy, central compartment dissection, parathyroid re-implantation, and adjuvant radiation therapy. Tumor DNA sequencing of 236 genes by FoundationOne panel found truncating mutations in PTEN and missense mutations in RET and TP53. However, patient-matched germline DNA was not sequenced which is critical for identification of true somatic mutations. Furthermore, the FoundationOne panel doesn't measure genomic rearrangements which have been shown to be abundant in sarcomas and are associated with sarcoma tumorigenesis and progression. In the current study, we carried out comprehensive genomic sequencing of the tumor, adjacent normal tissues, and patient-matched blood, in an effort to understand the genomic makeup of this rare extranodal FDCS and to identify potential therapeutic targets. Eighty-one somatic point mutations were identified in tumor but not in adjacent normal tissues or blood. A clonal truncating mutation in the CLTCL1 gene, which stabilizes the mitotic spindle, was likely a driver mutation of tumorigenesis and could explain the extensive copy number aberrations (CNAs) and genomic rearrangements in the tumor including a chr15/chr17 local chromothripsis resulted in 6 expressed fusion genes. The fusion gene HDGFRP3→SHC4 led to a 200-fold increase in the expression of oncogene SHC4 which is a potential target of the commercial drug Dasatinib. Missense mutations in ATM and splice-site mutation in VEGFR1 were also detected in addition to the TP53 missense mutation reported by FoundationOne.

The spectrum of localized amyloidosis: a case series of 20 patients and review of the literature.

Localized deposition of amyloid may occur in individual organs, in the absence of systemic involvement. The reason for localized deposition is unknown, but it is hypothesized that deposits result from local synthesis of amyloid protein, rather than the deposition of light chains produced elsewhere. We identified 20 cases of localized amyloidosis at our institution between 1993 and 2003. There were 11 males and nine females in the group. The mean age at the time of diagnosis was 65.5 years. Organs involved included skin, soft tissues, oropharynx, larynx, lung, bladder, colon, conjunctiva, and lymph node. In six of nine patients typed, the amyloid light chain was lambda. In those patients where follow-up was available (mean 7.6 years), none developed systemic disease. Localized amyloidosis occurs in a variety of organ systems. Evolution into systemic amyloidosis was not seen in our series of patients, supporting the hypothesis of local production of amyloid protein in these cases.

Solitary breast mass as initial presentation of clinically silent metastatic renal cell carcinoma.

Metastasis to the breast from extramammary tumors is rare. Breast metastases of renal cell carcinoma (RCC) origin have been described in sporadic case reports. We present a patient with a solitary breast mass representing the manifestation of clinically silent, metastatic RCC. A 76-year-old female was 12 years prior removed from radical nephrectomy for localized RCC. Her new breast mass was identified on physical examination. Pathology of the resected mass was diagnostic of metastatic RCC and subsequent imaging studies demonstrated a 1.9 cm renal mass in her solitary kidney. The patient elected subcutaneous Interleukin-2 immunotherapy as primary treatment for her recurrent RCC.

Imaging characteristics of bone graft materials.

Bone graft materials are widely used in reconstructive orthopedic procedures to promote new bone formation and bone healing, provide a substrate and scaffolding for development of bone structure, and function as a means for direct antibiotic delivery. Bone graft materials include autografts, allografts, and synthetic substitutes. An autograft (from the patient's own bone) supplies both bone volume and osteogenic cells capable of new bone formation. The imaging appearance of an autograft depends on its type, composition, and age. Autografts often appear as osseous fragments at radiography. At computed tomography (CT), autografts appear similar to the adjacent cortical bone. At magnetic resonance (MR) imaging, however, autografts have a variable appearance as a consequence of the viable marrow inside them, a feature not present in other graft materials. An allograft (from cadaveric bone) has an appearance similar to that of cortical bone on radiographs and CT images. An allograft in the form of bone chips or morsels does not show those features on radiographs and CT images, but instead appears as a conglomerate with medium to high opacity and attenuation within the bone defect. In the immediate postoperative period, allografts appear hypointense on both T1- and T2-weighted MR images. Hematopoietic tissue replaces the normal fatty marrow in the later phases of graft incorporation. Synthetic bone substitutes are much more variable in imaging appearance. As the use of bone allografts and synthetic substitutes increases, familiarity with postoperative imaging features is essential for differentiation between grafts and residual or recurrent disease.

Post-Transplant Lymphoproliferative Disorder Presenting as CD20-Negative Plasmablastic Lymphoma in the Lung.

Post-transplant lymphoproliferative disorders (PTLD) are a serious complication of transplantation with a high mortality. Most PTLD present within the first year of transplantation and are associated with Epstein-Barr virus (EBV) infection. Plasmablastic lymphoma (PBL) is a rare but aggressive disease originally described in patients with HIV, presenting most commonly in the jaw and oral mucosa. To our knowledge, this is the first case of PBL presenting as PTLD of the lung in a HIV and EBV negative patient. Given the increasing number of transplants performed, we would like to share this uncommon presentation of PTLD as PBL.

Hemodynamic Transesophageal Echocardiography-Guided Venous-Arterial Extracorporeal Membrane Oxygenation Support in a Case of Giant Cell Myocarditis.

Giant cell myocarditis (GCM) is a rare and commonly fatal form of fulminant myocarditis. During the acute phase, while immunosuppressive therapy is initiated, venoarterial extracorporeal membrane oxygenation (VA-ECMO) support is commonly used as a bridge to heart transplantation or recovery. Until recently, conventional transesophageal echocardiography and transthoracic echocardiography were the tools available for hemodynamic assessment of patients on this form of mechanical circulatory support. Nevertheless, both techniques have their limitations. We present a case of a 54-year-old man diagnosed with GCM requiring VA-ECMO support that was monitored under a novel miniaturized transesophageal echocardiography (hTEE) probe recently approved for 72 hours of continuous hemodynamic monitoring. Our case highlights the value of this novel, flexible, and disposable device for hemodynamic monitoring, accurate therapy guidance, and potential VA-ECMO weaning process of patients with this form of severe myocarditis.