Journal Article Degranulation of mast cells in dengue patients Get access LVS Asher, LVS Asher Walter Reed Army Institute of Research, Silver Spring, Maryland 20910-7500 Search for other works by this author on: Oxford Academic Google Scholar AS Norton, AS Norton Walter Reed Army Institute of Research, Silver Spring, Maryland 20910-7500 Search for other works by this author on: Oxford Academic Google Scholar S Krivda, S Krivda Department of Medicine, Walter Reed Army Medical Center, Washington DC 20307 Search for other works by this author on: Oxford Academic Google Scholar HK Wong, HK Wong Walter Reed Army Institute of Research, Silver Spring, Maryland 20910-7500 Search for other works by this author on: Oxford Academic Google Scholar MP Mammen, MP Mammen Walter Reed Army Institute of Research, Silver Spring, Maryland 20910-7500 Search for other works by this author on: Oxford Academic Google Scholar AG Lyons, AG Lyons Walter Reed Army Institute of Research, Silver Spring, Maryland 20910-7500 Search for other works by this author on: Oxford Academic Google Scholar S Thomas, S Thomas Department of Medicine, Walter Reed Army Medical Center, Washington DC 20307 Search for other works by this author on: Oxford Academic Google Scholar W Sun, W Sun Walter Reed Army Institute of Research, Silver Spring, Maryland 20910-7500 Search for other works by this author on: Oxford Academic Google Scholar KH Eckels, KH Eckels Walter Reed Army Institute of Research, Silver Spring, Maryland 20910-7500 Search for other works by this author on: Oxford Academic Google Scholar DW Vaughn DW Vaughn Walter Reed Army Institute of Research, Silver Spring, Maryland 20910-7500 Search for other works by this author on: Oxford Academic Google Scholar Microscopy and Microanalysis, Volume 8, Issue S02, 1 August 2002, Pages 920–921, https://doi.org/10.1017/S1431927602107288 Published: 01 August 2002
Both classic and atypical Spitz nevi are uncommon melanocytic lesions usually presenting in children and adolescents. The classic Spitz nevus typically is benign and has characteristic clinical and histologic features. In contrast, the atypical Spitz nevus has an unknown clinical prognosis, and its clinical and histologic traits are loosely defined. Melanoma can have similar features to both classic and atypical Spitz nevi and must be ruled out in all cases. We review the literature on classic and atypical Spitz nevi, advances in differentiating both types of nevi from melanoma, and treatment options.
Birt-Hogg-Dubé syndrome (BHDS) is a rare genodermatosis with cutaneous and systemic findings. We report the case of a 47-year-old woman with BHDS who presented with numerous facial papules and the more recently associated finding of pulmonary cysts. We review recent genetic discoveries and the cutaneous and systemic findings associated with this rare syndrome.
Plasma cell myeloma (PCM) constitutes approximately 10% of all hematologic malignancies, and usually evolves from a pre-malignant stage known as monoclonal gammopathy of undetermined significance.1 PCM is diagnosed when a patient has met criteria for a clonal bone marrow plasma cell neoplasm (PCN) with ≥10% involvement or extramedullary plasmacytoma and at least one myeloma-defining event (MDE). MDEs include the CRAB (hypercalcemia, renal failure, anemia, and lytic bone lesions) symptoms as well as additional biomarkers. More recent randomized control studies show PCM median overall survival (OS) to be approximately 6 years.1 For patients with autologous stem cell transplantation (ASCT), median OS improves by approximately 2 additional years.1 Regardless of transplant status, patients are frequently kept on maintenance therapy after the initial treatment. Unfortunately, remission is generally not durable in PCM, and the remission duration tends to shorten with each relapse. In PCM, the malignant plasma cells generally reside in the bone marrow but may enter peripheral circulation (plasma cell leukemia). Fewer than 1% of PCM patients have cutaneous involvement.2 In this case, we present an interesting report of a 70-year-old female who presented to her dermatologist with firm, pink papulonodules. The skin biopsy specimen showed atypical hematolymphoid cells infiltrating the dermis with an unusual immunohistochemical staining pattern, resulting in a diagnostically challenging case requiring correlation with clinical history. A 70-year-old female patient presented to her dermatologist with multiple firm, pink, nontender papulonodules randomly distributed on her flank, back, and upper thighs, measuring 5 to 6 mm in diameter (Figure 1). She denied other systemic complaints. The patient underwent a skin biopsy with the clinical impression of leukemia cutis vs atypical Sweet syndrome. FIGURE 1 The patient presented with multiple firm, pink papulonodules randomly distributed on her flank, back, and upper thighs, measuring 5 to 6 mm in diameter FIGURE 2 A, Infiltrative dermal neoplasm with uninvolved epidermis (H&E, ×40). B, The plasmablastic neoplastic cells near the epidermis are crowded, with large irregular nuclei, prominent nucleoli, and high nuclear to cytoplasmic ratio. Frequent atypical mitotic figures are present (H&E, ×600). C, The neoplastic cells deeper in the dermis show a plasmacytic morphology, with frequent bilobed and multilobated cells, some of which have a peri-nuclear clearing (H&E, ×600) On routine H&E staining (Figure 2), there was a diffuse dermal infiltrate of intermediate to large cells with high nuclear to cytoplasmic ratio, irregular nuclei, prominent nucleoli, and frequent atypical mitotic figures. The overlying epidermis was largely uninvolved. Deeper in the dermis, the neoplastic cells were discohesive and less crowded. They had moderate cytoplasm, some with a peri-nuclear clearing. Bilobed and multilobed neoplastic cells were abundant. A comprehensive panel of immunohistochemical stains was performed, with the tumor cells expressing strong diffuse CD4, weak CD56 (Figure 3), and strong bcl-2. The neoplastic cells were negative for CD45, CD3, CD20, bcl-6, CD30, CK7, CK20, AE1/AE3, desmin, Melan A, SOX10, S100, CD117, myeloperoxidase, CD34, and CD68. Ultimately, additional markers were added and showed the neoplastic cells to be strongly positive for CD138 with κ-restriction by κ/λ light chain immunohistochemical stains (Figure 4). After review of the immunohistochemical staining results, we obtained additional clinical information from the clinician that was not present on the original requisition form: The patient was first diagnosed with kappa light chain multiple myeloma 4 years ago and treated with chemotherapy. One year into treatment, the patient received a stem cell transplant, and was kept on maintenance therapy with presumed well-controlled disease. This clinical history supports the diagnosis of cutaneous involvement by myeloma and excludes the diagnosis of primary extramedullary plasmacytoma (PEMP), a rare PCN involving soft tissue only, with the absence of bone marrow involvement or other systemic symptoms of multiple myeloma.3 The patient was admitted to the hospital to begin treatment following the diagnosis of cutaneous PCM. A month into chemotherapy, the patient had a bone marrow biopsy showing residual PCM: CD138 highlighted the plasma cells in the marrow (<5% of marrow cellularity) which were kappa-restricted. Because of residual disease, the patient was initiated on chimeric antigen receptor T-cell (CAR-T) therapy, resulting in resolution of the cutaneous lesions a week after therapy. Cutaneous involvement of PCM is rare and typically a late-stage disease event although it has also been documented as the presenting sign.4 Monoclonal light chain studies show κ-restriction to be more frequent than λ-restriction in cutaneous PCM, with serum electrophoresis studies to be 100% concordant with the immunohistochemical κ/λ staining pattern.4, 5 The clinical presentation includes violaceus papules, nodules, and plaques.4, 6 The trunk is most frequently affected, with head and extremities less often involved.4, 6, 7 Unfortunately, most patients do not survive beyond 1 year after skin involvement.4, 6, 7 Cutaneous involvement by PCM has diverse histopathologic patterns, including plasmacytic (mature-appearing plasma cells), plasmablastic (immature), and lymphoplasmacytic (mature with scant cytoplasm, resembling lymphocytes).6 Sarcomatoid and spindle plasma cell morphologies have also been described.7 In cases where the morphology is not always reliable, immunohistochemical stains can better elucidate the cell lineage. In our case, routine histopathology suggested a hematolymphoid process because of the discohesive and blastic appearance of the cells, and negative epithelial and melanocytic differentiation markers. Based on the H&E morphology coupled with expression of CD4 and CD56, the differential diagnosis included blastic plasmacytoid dendritic cell neoplasm (BPDCN), formerly known as CD4/CD56 hematodermic neoplasm. BPDCN is derived from the precursors of plasmacytoid dendritic cells and is an aggressive hematologic neoplasm that commonly involves the skin. Histopathology is characterized by diffuse infiltrates of medium-sized cells resembling lymphoblasts or myeloblasts. The neoplastic cells express CD4, CD56, CD123, and TCL-1, bcl-2 and are negative for CD3, CD34, CD20, CD10, CD30, myeloperoxidase, and bcl-6.8, 9 Most cases show a dot-like pattern with CD68, which was negative in our case.9 The positive labeling for CD4 also raised the possibility of T-cell lymphoma. Skin involvement has been described in 20% to 70% of mature T-cell leukemias including adult T-cell leukemia (ATLL), T-cell prolymphocytic leukemia (T-PLL), and Sézary syndrome (SS).10 ATLL is a neoplasm of mature CD4+ T lymphocytes associated with human T-cell lymphotropic virus type I (HTLV-1) which may show heterogeneous and/or pleomorphic lymphocytes.10 T-PLL frequently involves the face, and biopsy will reveal small to medium-sized lymphocytes with a perivascular and periadnexal predilection.10 Finally, SS is a clonal T-lymphoproliferative disorder presenting with erythroderma, generalized lymphadenopathy, and blood involvement. SS skin biopsies would show perivascular and/or interstitial dermal infiltration by small to medium lymphocytes, frequently with epidermotropism.10 However, in all these T-cell neoplasms, CD3 is typically positive (but was negative in this case), often along with other T-cell markers. The strong bcl-2 expression and plasmacytoid morphology can be seen in plasmacytoid cutaneous marginal zone lymphoma and lymphoplasmacytic lymphoma. Although cutaneous marginal zone lymphoma and lymphoplasmacytic lymphoma tend to be positive for bcl-2, they are also typically positive for CD20.11 Although a diagnostic pitfall can occur when CD20 expression is lost following anti-CD20 therapy (rituximab).12 Finally, the differential diagnosis could include plasmablastic lymphoma (PBL), an aggressive B-cell lymphoma with frequent loss of CD20 expression and positivity for plasma cell markers such as CD38 or CD138.13, 14 This entity is typically restricted to HIV-positive patients and is often associated with Epstein-Barr virus positivity. In our case, the patient is negative for HIV. The cells deeper in the dermis had a more plasmacytoid appearance than the blast-like cells near the epidermis, so staining with CD138 and light chains was performed, and the neoplastic cells labeled as κ-restricted, CD138-positive plasma cells. This immunohistochemical staining pattern was in concordance with the commonly observed immunophenotype of PCM, characterized by the absence of pan-B marker CD20 and abnormal gain of CD56.15, 16 While normal plasma cells do not express CD56, the neoplastic plasma cells of PCM are generally positive for CD56; the prognostic implications of CD56 positivity are still being evaluated.17 Despite its common utility as a pan-leukocyte marker, CD45 is frequently negative in PCNs, particularly in advanced disease.15 The only immunohistochemical staining exception in our case was the aberrant CD4 positivity, which is a well-established T-cell lineage marker. Various B-cell lymphomas have been documented to gain abnormal expression of T-cell markers such as CD5, CD7, and CD8.18, 19 However, the plasma cells of PCNs originate from terminally differentiated B-cells, and their expression of T-cell markers is exceedingly rare, with limited cases reported in literature.20-23 Gain of CD4 can be accompanied by gain of CD3; however, the significance and pathogenesis of these T-cell markers in PCNs are unclear.20, 22 Concurrent amyloid deposition in PCM would offer a clue to diagnosis,6 but usually occurs in the bone marrow and was not observed in our patient's skin biopsy specimen. Rare reports documenting cutaneous immunoglobulin-related deposits in PCM have been described including crystal-storing histiocytosis, cryoglobulinemia, and crystalglobulinemia.24-26 In summary, we present a case of a 70-year-old female with pink, firm, nontender papulonodules in a random distribution around the flank, back, and upper thighs. Our case is particularly challenging because the morphology was of largely plasmablastic with focally plasmacytic appearing neoplastic cells. Although our initial suspicion of a hematologic neoplasm was correct, the abnormal CD4 expression was a diagnostic pitfall. Ultimately, correlation of histopathology, immunohistochemistry, and clinical history confirmed the diagnosis of cutaneous involvement by PCM. The authors have no conflicts of interest. Data sharing not applicable to this article as no datasets were generated or analyzed during the current study
Anthrax is occasionally encountered by U.S. military physicians in the deployed setting, where limited resources make it difficult to obtain laboratory confirmation. We present a case of cutaneous anthrax diagnosed using a ruggedized polymerase chain reaction device in austere combat conditions.
