Elizabeth Sagatys

Rosai-Dorfman Disease: Tumor Biology, Clinical Features, Pathology, and Treatment

BACKGROUND Rosai-Dorfman disease (RDD) is a rare, nonmalignant clinical entity characterized by a group of clinical symptoms and characteristic pathological features. METHODS Articles that reviewed tumor biology, clinical features, pathology, and treatment for RDD were identified in a search of the literature for the years 1990 to 2014. The results from this body of literature were reviewed and summarized. RESULTS Patients with RDD generally present with massive, painless cervical lymphadenopathy, fevers, and elevated inflammatory markers. Extranodal disease is typical, with the most common sites being the skin and the central nervous system. Rarely, the gastrointestinal tract is involved. Immunohistochemistry remains the mainstay of diagnosis with S100 and CD68 positive cells while CD1a will be negative of involved histiocytes. Histologically, the disease shows the classical characteristic finding of emperipolesis. Many patients do not require treatment; however, surgical resection remains the mainstay of treatment for symptomatic disease. The role of steroids, chemotherapy, and radiation therapy continue to be based on small case series and case reports. CONCLUSIONS RDD has a variable clinical presentation; therefore, a high degree of suspicion and a thorough pathological review are necessary to diagnose this rare clinical entity. Although some patients will experience spontaneous resolution, others may require surgical resection or steroid therapy and radiation or chemotherapy. Given the rarity of the disease and the lack of a clear therapeutic pathway, referring patients to a tertiary center is recommended for confirming the diagnosis and treatment considerations.

Dendritic cell and histiocytic neoplasms: biology, diagnosis, and treatment.

BACKGROUND Dendritic and histiocytic cell neoplasms are rare malignancies that make up less than 1% of all neoplasms arising in lymph nodes or soft tissues. These disorders have distinctive disease biology, clinical presentations, pathology, and unique treatment options. Morphology and immunohistochemistry evaluation by a hematopathologist remains key for differentiating between these neoplasms. In this review, we describe tumor biology, clinical features, pathology, and treatment of follicular dendritic cell sarcoma, interdigitating dendritic cell sarcoma, indeterminate dendritic cell sarcoma, histiocytic sarcoma, fibroblastic reticular cell tumors, and disseminated juvenile xanthogranuloma. METHODS A literature search for articles published between 1990 and 2013 was undertaken. Articles are reviewed and salient findings are systematically described. RESULTS Patients with dendritic cell and histiocytic neoplasms have distinct but variable clinical presentations; however, because many tumors have recently been recognized, their true incidence is uncertain. Although the clinical features can present in many organs, most occur in the lymph nodes or skin. Most cases are unifocal and solitary presentations have good prognoses with surgical resection. The role of adjuvant therapy in these disorders remains unclear. In cases with disseminated disease, prognosis is poor and data on treatment options are limited, although chemotherapy and referral to a tertiary care center should be considered. Excisional biopsy is the preferred method of specimen collection for tissue diagnosis, and immunohistochemistry is the most important diagnostic method for differentiating these disorders from other entities. CONCLUSIONS Dendritic cell and histiocytic cell neoplasms are rare hematological disorders with variable clinical presentations and prognoses. Immunohistochemistry remains important for diagnosis. Larger pooled analyses or clinical trials are needed to better understand optimal treatment options in these rare disorders. Whenever possible, patients should be referred to a tertiary care center for disease management.

Lymphoid lost and found.

We present the clinicopathologic features of a case initially interpreted as lymphocytoma cutis that was later determined to be lymphoepithelioma-like carcinoma of the skin. The histologic presence of nodular aggregates of undifferentiated epithelioid cells surrounded by a dense, reactive lymphocytic infiltrate should prompt consideration of the diagnosis of lymphoepithelioma-like carcinoma of the skin. This lesion should be distinguished from lymphocytoma cutis, B-cell lymphoma, and cutaneous lymphadenoma.

PRIMARY CUTANEOUS B-CELL LYMPHOMA IN A CHILD

Primary cutaneous B-cell lymphoma is a B-cell lymphoma of the skin with no evidence of extracutaneous involvement at the time of diagnosis. In this report, we describe an 8-year-old boy who presented with a firm, alopecic, skin-colored, smooth nodule over the right frontal scalp. Histological examination revealed a mid-to deep-dermal mononuclear lesion. Immunohistochemical staining revealed a B-cell population that was CD10(+), CD5(−), CD21(+), and bcl2(−). This pattern of reactivity is characteristic of primary cutaneous B-cell lymphoma of follicle-center subtype. To the best of our knowledge, this is the first report of this type of cutaneous lymphoma in a child.

55-YEAR-OLD MAN WITH A PARASPINAL MASS

A 55-year-old man presented for a routine preoperative chest X-ray in preparation for a knee replacement. Imaging revealed an extrapleural paraspinal mass in the region of T8. Fine needle aspiration of the mass was interpreted as melanoma. Neurologic examination was unremarkable. Total body skin examination failed to reveal any suspicious pigmented lesions. The mass was in close connection with the exiting T8 nerve root and somewhat adherent to the sympathetic chain. The mass was removed within an intact capsule. Immunohistochemical staining and electron microscopy of the resected specimen revealed a malignant melanotic schwannoma. The features of melanotic schwannoma, both benign and malignant variants, and their distinction from melanoma are discussed. Correspondence 635 Brain Pathology 18 (2008) 631–635

Acral keratosis with eosinophilic dermal deposits: a distinctive clinicopatholgic entity or colloid milium redux?

Aims:  The differential diagnosis of acral keratoses is broad. Encompassing a variety of infectious, heritable and degenerative disorders, emphasis upon the clinical setting and histologic subtlety are often required to arrive at the correct diagnosis. Herein, we report on a series of adult patients who presented with agminated or solitary papules of the distal finger found on histologic examination to contain amorphous eosinophilic deposits.

What is it? Unusual interstitial fibrohistiocytic tumor or other.

Fibrohistiocytic lesions are capable of presenting in a variety of histologic guises. We have recently encountered two lesions that similarly showed a hitherto described proliferation of atypical spindled and stellate cells with a distinctive deep dermal and interstitial distribution. The pathogenic significance and nosologic status of this neoplasm is unknown.

In vivo IL-12/IL-23p40 neutralization blocks Th1/Th17 response after allogeneic hematopoietic cell transplantation

T-helper 1 and T-helper 17 lymphocytes mediate acute graft-versus-host disease (GvHD). Interleukin 12 is critical for T-helper 1 differentiation and interleukin 23 for T-helper 17 maintenance. Interleukin 12 and 23 are heterodimeric cytokines that share the p40 subunit (IL-12/IL-23p40). In a randomized, blinded, placebo-controlled trial, we examined the biological impact and clinical outcomes following IL-12/IL-23p40 neutralization using ustekinumab. Thirty patients received peripheral blood mobilized hematopoietic cell transplantation (HCT) from HLA-matched sibling or unrelated donors, received sirolimus plus tacrolimus as GvHD prophylaxis, and were randomized to ustekinumab versus placebo with 1:1 allocation after stratification by donor type. The primary end point of the trial was the mean percentage (%) T-regulatory (Treg) cells on day 30 post HCT. Ustekinumab was delivered by subcutaneous injection on day −1 and day +20 after transplantation. On day 30 post transplant, no significant difference in % Treg was observed. Ustekinumab suppressed serum IL-12/IL-23p40 levels. Host-reactive donor alloresponse at days 30 and 90 after transplantation was polarized with significant reduction in IL-17 and IFN-α production and increase in IL-4. No toxicity attributed to ustekinumab was observed. Overall survival and National Institute of Health moderate/severe chronic GvHD-free, relapse-free survival were significantly improved among ustekinumab-treated patients. No significant improvements were observed in acute or chronic GvHD, relapse, or non-relapse mortality. These data provide first evidence that IL-12/IL-23p40 neutralization can polarize donor anti-host alloresponse in vivo and provide initial clinical efficacy evidence to be tested in subsequent trials. (Trial registered at clinicaltrials.gov identifier: 01713400.)

Follicular Lymphoma With Progression to Diffuse Large B-Cell Lymphoma and Concurrent CD5-Negative Mantle Cell Lymphoma-3 Entities in a Lymph Node

A 68-year-old woman with a history of follicular lymphoma had pathological findings of grade 3B follicular lymphoma, mantle cell lymphoma (MCL), and diffuse large B-cell lymphoma (DLBCL) identified in 1 lymph node. The DLBCL appeared to be a transformation of the follicular lymphoma. The nodules were diffusely and strongly positive for CD20, BCL6, and BCL2. CD43 highlighted smaller lymphocytes in a fraction of the nodules. BCL1 staining was variable with a mixture of nodular and mantle zone patterns. The diffuse areas showed weaker positivity for CD10, BCL2, and BCL6. CD3 and CD5 highlighted intermixed T cells. The Ki-67 proliferative index was overall estimated to be 60%. Fluorescent in situ hybridization performed on the lymph node was positive for CCND1/IGH. The patterns of BCL1 and BCL6 staining demonstrated 2 separate populations of neoplastic B lymphocytes.