Cat Scratch Disease and Acquired Immunodeficiency Disease: Diagnosis by Transmission Electron Microscopy

A 33-year-old, homosexual, cat-owning, African-American man with human immunodeficiency virus infection by positive serologic tests and acquired immunodeficiency syndrome by CD4 lymphocyte count alone (39 cells/mL) presented with a one-year history of intermittent fever, weight loss, and generalized lymphadenopathy. A malignant lymphoma was suspected clinically. Light microscopic study of a left inguinal lymph node biopsy specimen revealed effacement of the lymph node architecture by a diffuse infiltrate of large, atypical reticulum cells, loose, patchy granulomatous inflammation, diffuse hyaline fibrosis, diffusely proliferated blood vessels, and multifocal degeneration and necrosis. Lymph follicles were absent and lymphocytes were moderately depleted. Microorganisms were not seen in lymph node sections stained with special histochemical stains (including the War-thin-Starry stain). These light microscopic changes were considered suggestive of a malignant lymphoma, especially Hodgkin's disease. The diagnosis of cat scratch disease (CSD) became apparent only after transmission electron microscopic study of the lymph node revealed clusters of small, pleomorphic bacteria in degenerated collagenous tissue and in blood vessel walls. This case illustrates the value of transmission electron microscopy in making the diagnosis of CSD, especially when light microscopic changes are superimposed on those of late human immunodeficiency virus infection of the lymph node.     

Inflammatory pseudotumor of lymph nodes presenting as pyrexia of unknown origin

Inflammatory pseudotumor (IPT) is an uncommon benign disorder characterized by proliferation of spindle cells, inflammatory cells, and small vessels. The IPT of lymph nodes is a rare cause of lymphadenopathy that usually affects one or two nodal groups. We describe a 27-year-old male presenting with generalized lymphadenopathy, hepatosplenomegaly and fever for 1 year. Histologic examination of lymph node revealed few remnant lymphoid aggregates with marked sclerosis and numerous anastomosing blood vessels in lymph node parenchyma. Interspersed in between the fibrotic bands was a polymorphic infiltrate composed of lymphocytes, plasma cells, eosinophils, and immunoblasts. Also, many histiocytes, multinucleated giant cells some being Langhan's type and at places forming ill-defined granulomas were observed. The presence of granulomas and Langhan's type of giant cells can lead to a misdiagnosis of tuberculosis as was also done in the present case. It is thus not only important to be aware of this rare benign pathologic entity while dealing with a case of lymphadenopathy, but also consider it in the differential diagnosis of granulomatous disease.     

T-cell lymphoblastic leukemia/lymphoma with t(7;14)(p15;q32) [TCRγ-TCL1A translocation]: a case report and a review of the literature

A 22-year-old man sought medical advice for a swelling in the right side of the neck in December 2011. Histopathological examination of the lymph node biopsy initially suggested reactive lymphadenitis, on account of the only sparse presence of tumor cells. Bone marrow examination was performed in February 2012 revealed findings consistent with a diagnosis of T-cell lymphoblastic leukemia/lymphoma (T-LBL), and the patient was begun on remission induction therapy. The bone marrow showed an immature thymocytic pattern: cytoplasmic CD3⁺, surface CD3^-, CD5⁺, CD4^-, and CD8^-. Re-assessment of the lymph node specimens revealed the same phenotype of the cells in the lymph node as that of the blasts in the bone marrow. In addition, a chromosomal aberration t(7;14)(p15;q32) was noted. The lymph node biopsy specimens were examined by paraffin-embedded tissue section-fluorescence in situ hybridization (PS-FISH), which revealed a fusion signal of T-cell receptor (TCR)γ gene (7p15) with T-cell leukemia/lymphoma 1A (TCL1A) gene (14q32.13). There have been at least 10 reported cases of T-LBL with t(7;14)(p15;q32), including the present case. However, this is the first reported case in which TCRγ-TCL1A translocation was confirmed by FISH.     

Inflammatory pseudotumor of lymph nodes: clinicopathologic and immunohistological study of 11 Japanese cases

We report 11 Japanese cases of inflammatory pseudotumor (IPT) of the lymph node. There were 7 males and 4 females with ages ranging from 5 to 68 years (median; 48). Only 2 patients had systemic lymphadenopathy, and all others had involvement of only 1 lymph node group. Constitutional symptoms such as fever were present in 8 patients and laboratory abnormalities were detected in 5. All patients recovered and were alive and well after 2 to 180 months (median; 32 months). Histologically, the process mainly involved the connective tissue framework of the lymph node, secondarily spreading into the lymph node parenchyma and the perinodal tissue. It was characterized by a storiform growth pattern of myofibroblasts, marked vascularity with associated vascular lesions, and a polymorphous reactive cellular infiltrate in a collagen-rich stroma. An immunohistochemical study revealed numerous myofibroblasts, histiocytes, and vascular endothelial cells expressing vascular endothelial growth factor (VEGF) in 6 cases. It was suggested that VEGF may be involved, in part, in the induction of the angiogenesis of IPT. Moreover, the present study indicates that follicular dendritic cell sarcoma, nasal T/natural killer cell lymphoma, and anaplastic large cell lymphoma should be added to the differential diagnosis from IPT of the lymph node. Int J Surg Pathol 9(3):207-214, 2001     

Evaluation of FoxP3 expression in peripheral T-cell lymphoma

Peripheral T-cell lymphomas (PTCLs) are biologically heterogeneous and have not been successfully correlated with specific T-cell subsets. We investigated PTCL, not otherwise specified (NOS), angioimmunoblastic T-cell lymphoma (AILT), and anaplastic large cell lymphoma (ALCL) cases for FoxP3 expression to determine a potential derivation from regulatory T (Treg) cells. One PTCL-NOS case strongly expressed FoxP3 in the neoplastic T cells and showed unusual histomorphologic features with a dense infiltration of the lymph node by immunoblastic T cells and almost no reactive background infiltrate. The patient died shortly after diagnosis, suggesting that biologic properties of Treg cells may have contributed to the rapidly fatal clinical course. All remaining PTCL-NOS and AILT cases showed FoxP3 positivity only in the reactive infiltrate. Among ALCL cases, 4 of 6 ALK+ cases displayed weak and inhomogeneous FoxP3 expression in the tumor cells. FoxP3+ PTCL-NOS presumably derived from bona fide Treg cells occurs but seems rare in the Western population.     

Nodal marginal zone lymphoma associated with extensive epithelioid histiocytes

Nodal marginal zone lymphoma (NMZL) is a rare type of non-Hodgkin lymphoma. In this report, we describe a similar condition affecting female 53-year-old presented with generalized lymphadenopathy and high LDH level. The patient underwent excision of cervical lymph node and bone marrow biopsy. Histopathological examination of the excised lymph node revealed florid infiltrate by epithelioid histiocytes, which greatly underscores the neoplastic process directing the diagnosis towards reactive lesions such as toxoplasmosis, marginal zone hyperplasia or monocytoid B-cell hyperplasia. Careful histopathological examination of interfollicular and parafollicular regions helped in recognition of the pale monomorphic neoplastic cells that showed immunoreactivity for CD20 and Bcl-2 and lacked expression for CD5, CD10 and CD23. The involvement of bone marrow by the same type of cells has excluded the possibility for reactive conditions. The recognition of NMZL is sometimes difficult when benign components predominate such as the presence follicular hyperplasia and epithelioid cell clusters. However, full clinical data including LDH level and asking for bone marrow biopsy were greatly helpful in identifying the correct lesion.     

The great masquerader: Kikuchi-Fujimoto disease presenting as fever of unknown origin

IntroductionKikuchi-Fujimoto (KF) disease, also known as necrotizing histiocytic lymphadenitis, is a rare cause of fever of unknown origin. Most commonly seen in Japanese populations, it presents with fever and diffuse lymphadenopathy. KF can present a diagnostic challenge as its presentation can mimic sepsis, autoimmune disease, and/or malignancy. We present a case of KF disease presenting with innumerable pulmonary nodules and suspected sepsis.Case reportA 24-year old African-American male inmate with no past medical history presented to the Emergency Department with two witnessed generalized tonic-clonic seizures. Initial vitals were notable for a fever of 101.5 F, tachycardia, and tachypnea. He was lethargic with a diffuse, erythematous, scaly, necrotic rash. Additionally, cervical, axillary, and inguinal mobile, non-tender lymph nodes were noted. Laboratory studies revealed white blood cells 1.9 × 10 3 cells/μL with 25% bands, hemoglobin 9.4 G/dL, and platelet count of 110 × 10 3 cells/μL. He was subsequently admitted for sepsis due to presumed meningitis and started on broad-spectrum antibiotics. Lumbar puncture revealed no pleocytosis. Peripheral blood smear showed bandemia with Pelger Huet cells. Computed Tomography of chest, abdomen, and pelvis with contrast revealed diffuse pulmonary nodules involving all lobes of the lungs in addition to bulky hilar and retroperitoneal lymphadenopathy. Interventional Radiology performed a retroperitoneal lymph nodes biopsy that revealed lymphoplasmacytic cell infiltrate with extensive necrosis. Otolaryngology performed an excisional biopsy of a lymph node, which showed histiocytic necrotizing lymphadenitis. The final diagnosis was Kikuchi-Fujimoto disease, also known as histiocytic necrotizing lymphadenitis.OutcomeThe patient completed a 7-day course of empiric antibiotics. Workup for infectious etiologies was negative. The patient had a repeat CT of the chest with interval resolution of his pulmonary nodules on outpatient follow-up.ConclusionPatients with innumerable pulmonary nodules and fever of unknown origin should be evaluated early in their hospital course for KF as early diagnosis can reduce excessive testing and shorten hospital stay.     

The lymph as a pool of self-antigens

Prenodal lymph is generated from the interstitial fluid that surrounds organs, and thus contains products of organ metabolism and catabolism. New proteomic analyses of lymph have identified proteins and peptides that are derived from capillary extravasation and tissue-specific proteins. Many of these peptides are detected at nanomolar concentrations in the lymph before passage through a regional lymph node. Before entering the node and once inside, proteins and processed peptides are filtered from the lymph by circulating immature dendritic cells (DCs) or non-activated nodal antigen-presenting cells (APCs) (macrophages, B cells and immature DCs). Here, we suggest that this process ensures organ-specific self-antigens are displayed to circulating and nodal APCs, thus contributing to the maintenance of peripheral tolerance.     

Peripheral T-cell lymphoma mimicking marginal zone B-cell lymphoma.

Peripheral T-cell lymphoma (PTCL) may assume a variety of histologic and cytologic appearances. We describe eight cases of PTCL morphologically simulating marginal zone B-cell lymphoma. We reviewed PTCL cases diagnosed in our institution between 1990 and 2000 and selected eight cases for study based on the following criteria: small-cell morphology with abundant, clear cytoplasm and either marginal zone involvement by the neoplastic infiltrate in lymph node biopsies or lymphoepithelial lesions in extranodal biopsies. Histologic features and ancillary studies were reviewed. Patients included six women and two men with a median age of 53 years (range, 35 to 74 years). Six patients were diagnosed with primary nodal PTCL, and two presented with primary extranodal disease. The original diagnosis was PTCL in only four cases; three cases were diagnosed as atypical lymphoid infiltrate, and one case as benign lymphoepithelial lesion. Lymph node biopsies revealed partial effacement of the architecture with residual follicles surrounded by the neoplastic small cells. Extranodal sites included hard palate, tongue, tonsil, and submandibular glands; all but one case demonstrated lymphoepithelial lesions. Monoclonality was demonstrated in six of eight cases (rearrangement of T-cell receptor gene), and three of eight had an aberrant T-cell population by flow cytometry. The differential diagnosis of atypical lymphoid infiltrates with morphologic features of marginal zone B-cell lymphoma should include PTCL. This uncommon morphological mimicry should be recognized, because PTCL is an aggressive disease regardless of morphology and should be treated accordingly.     

Cytologic features and frequency of plasmacytoid dendritic cells in the lymph nodes of patients with histiocytic necrotizing lymphadenitis (Kikuchi‐Fujimoto disease)

Histiocytic necrotizing lymphadenitis (HNL), also known as Kikuchi‐Fujimoto disease, is a benign and self‐limiting disease. It is histologically characterized by nodal lesions that show the infiltration of histiocytes, lymphoid cells, myeloid dendritic cells (mDCs), and plasmacytoid dendritic cells (pDCs), along with either apoptotic or karyorrhexic nuclear debris. pDCs have been proposed to be lymphoid early‐committed immature DCs which are positive for CD123, CD303, CD68, and HLA‐DR but negative for fascin, a mature DC marker, as well as CD13 and CD33,which are mDC markers. In the present study, we analyzed the cytomorphologic features and frequency of pDCs in the lymph nodes of HNL patients. Because the cytologic apprearance of pDCs with Papanicolau staining was quite similar to that of large lymphocytes, immunocytochemistry against CD123 was necessary for the distinction of pDCs. Counting the number of CD123‐positive pDCs in the HNL lymph nodes revealed that pDCs more frequently infiltrated the lymph nodes in the setting of HNL than in either reactive lymphadenitis or T and B cell lymphoma. In addition, interestingly, the numberof pDCs did not depend on the age of the HNL lesion, thus suggesting that pDCs are excellent indicators for the cytologic diagnosis of HNL. Diagn. Cytopathol. 2010. © 2009 Wiley‐Liss, Inc.     

Sinus Histiocytosis with Massive Lymphadenopathy: A Case Report with Pleural Effusion and Cervical Lymphadenopathy

Sinus histiocytosis with massive lymphadenopathy (SHML) is a rare disorder characterized by a nonneoplastic proliferation of distinctive histiocyte cells within lymph node sinuses and lymphatics in extranodal sites. SHML occurs worldwide and is primarily a disease of childhood and early adulthood. A 26-yr-old man presented with painless palpable lymph node in cervical area. Radiographic studies revealed pleural effusion with lymphadenopathy and calcification in mediastinum. The cervical lymph node biopsy showed dilated sinuses filled with histiocytes with clear cytoplasm. The cells stained positive with CD68 and S-100. These cytologic and immunohistochemical findings were considered consistent with the diagnosis of SHML.     

Development of different mast cell types in the opossum Didelphis albiventris

Previous studies have disclosed three types of mast cell in opossums: connective tissue (CTMC), mucosal (MMC), and lymphatic sinus (LSMC). In contrast to most opossum lymph nodes, the mesenteric lymph node is virtually devoid of LSMC, displaying medullary cord CTMC. The present study aimed to describe the development of these mast cell populations. Toluidine blue staining and a histochemical method for demonstrating heparin allowed the identification of immature and mature mast cells. Immature CTMC devoid of detectable heparin were rare until postnatal day 10. Mature CTMC filled with heparin-containing granules became numerous by day 30 to day 40. In the ileum, despite the presence of mature CTMC in the submucosa and mucosa (villus base), immature mast cells first appeared in the villus core by day 65 and adult features were apparent by day 100. In LSMC-containing lymph nodes, immature mast cells were found in lymphatic sinuses by day 10. Clear signs of LSMC differentiation were observed from day 20. Compared with the 10-day value, the mean diameter of cytoplasmic granules at day 40 had doubled and that at day 110 had tripled. In the mesenteric lymph nodes, immature mast cells differentiated into lymphatic sinus CTMC-like cells. After day 80, most of them were located in medullary cords. Weaning and complete maturation of mucosa preceded the differentiation of MMC. In lymph nodes, LSMC differentiation occurred in parallel with the development of the medullary region and deep cortex units.     

Development of different mast cell types in the opossum<Emphasis Type="Italic"> Didelphis albiventris</Emphasis>

Previous studies have disclosed three types of mast cell in opossums: connective tissue (CTMC), mucosal (MMC), and lymphatic sinus (LSMC). In contrast to most opossum lymph nodes, the mesenteric lymph node is virtually devoid of LSMC, displaying medullary cord CTMC. The present study aimed to describe the development of these mast cell populations. Toluidine blue staining and a histochemical method for demonstrating heparin allowed the identification of immature and mature mast cells. Immature CTMC devoid of detectable heparin were rare until postnatal day 10. Mature CTMC filled with heparin-containing granules became numerous by day 30 to day 40. In the ileum, despite the presence of mature CTMC in the submucosa and mucosa (villus base), immature mast cells first appeared in the villus core by day 65 and adult features were apparent by day 100. In LSMC-containing lymph nodes, immature mast cells were found in lymphatic sinuses by day 10. Clear signs of LSMC differentiation were observed from day 20. Compared with the 10-day value, the mean diameter of cytoplasmic granules at day 40 had doubled and that at day 110 had tripled. In the mesenteric lymph nodes, immature mast cells differentiated into lymphatic sinus CTMC-like cells. After day 80, most of them were located in medullary cords. Weaning and complete maturation of mucosa preceded the differentiation of MMC. In lymph nodes, LSMC differentiation occurred in parallel with the development of the medullary region and deep cortex units.     

FNAC in a case of NHL presenting initially as nodal infarction

Lymph node infarction is rare and can occur in either nonneoplastic or neoplastic conditions. Fine needle aspiration cytology (FNAC) of infarction preceding lymphoma has not been described earlier. A 26-year-old male, was referred to the cytology laboratory for FNAC of bilateral axillary lymph nodes. FNA smears showed uniform looking ghost cells. There were no viable cells. A biopsy was advised which also showed extensive coagulative necrosis. Five weeks later, right cervical lymph nodes also appeared and FNA smears showed discrete monomorphic population of immature lymphoid cells. A cytologic diagnosis of infarction in a case of non-Hodgkin's lymphoma (NHL) was made and subsequently confirmed by histopathologic examination. Our case indicates that such cases should be followed up closely and repeated aspirations should be done to prevent a delayed diagnosis of lymphoma.     

T cell receptor gamma/delta expression on lymphocyte populations of breast cancer patients.

The quantitative distribution and phenotype of gamma/delta lymphocytes in the peripheral blood (PBL), tumour draining lymph node (LNL) and tumour infiltrating lymphocytes (TIL) from breast carcinoma patients were determined by one- and two-colour flow cytometry. The TCR-gamma/delta + cells generally expressed the T cell lineage antigen CD3. The proportions of such cells were variable but generally small from all the three sources. Phenotypic analysis revealed that the CD8 marker was consistently and predominantly observed on gamma/delta + CD3+ cells in the tumour infiltrate, whereas CD4 expression, while generally low, was noted on a significant percentage (median 10%) of LNL gamma/delta + lymphocytes. In both PBL and LNL the predominant gamma/delta cell population was CD4-8-.     

Cervical lymph node metastasis of ovarian dysgerminoma: A case report with fine needle aspiration cytology

Dysgerminoma is a rare germ cell tumor, accounting for 1% to 2% of all malignant ovarian tumors. Here, we report a case of dysgerminoma diagnosed by aspiration cytology of a cervical lymph node. A 20‐year‐old woman presented with an abdominal mass and left cervical swelling. CT revealed a large pelvic tumor, along with a nodular lesion on the left side of neck. Fine needle aspiration (FNA) cytology of a cervical lymph node showed large atypical cells and small lymphocytes. Immunocytochemical staining on cell block material revealed that these large tumor cells were positive for placental alkaline phosphatase, D2‐40, and c‐kit. Dysgerminoma was suggested by FNA cytology. Furthermore, bilateral oophorectomy was performed, and histology confirmed the diagnosis of ovarian dysgerminoma. FNA cytology of metastatic lymph nodes along with immunocytochemistry is a useful tool for diagnosis of dysgerminoma.     

Classic follicular dendritic reticulum cell tumor of the lymph node developing in a patient with a previous inflammatory pseudotumor-like proliferation

Inflammatory pseudotumor (IPT) and follicular dendritic reticulum cell tumor (FDRCT) are rare entities of the lymph node characterized by spindle-cell proliferation. We report a case of a 31-year-old woman, who was admitted for biopsy of a lymph node in the left submandibular area. The microscopic examination revealed a proliferation of spindle cells, partially replacing the normal lymph node architecture, suggestive of an IPT. The preserved peripheral portion showed follicular hyperplasia with Castleman-like appearance. Six years later she presented with a new enlargement in the same submandibular area. The nodule was removed, and a diagnosis of a classic FDRCT of the lymph node was made. The present case is remarkable, and clinicopathological data show that IPT-like proliferations could be in some case an early presentation of FDRCT.     

Murine lymph nodes in response to the local administration of dextran sulphate

In mice a single injection of 4 mg of Dextran sulphate within a few days produces an enlargement of area draining lymph nodes and activates basophils/mast cells. This activation is manifested by many-fold increase of mast cell number per lymph node, degranulation of mast cells and appearance of young, immature mast cells capable to synthetize new granules. In contrast to the lymph nodes, the Dextran-injected connective tissue mast cells remained unchanged. This suggest that Dextran sulphate directly activates lymph node mast cells, probably by activation of T-cell suppressor or macrophages.