Plasmacytoid Cells Research Articles

Antibody responses initiated by Clec9A-bearing dendritic cells in normal and Batf3−/− mice

Injection of antigens coupled to antibodies against the dendritic cell (DC) surface molecule Clec9A has been shown to produce strongly enhanced antibody responses even without co-administration of adjuvants, via antigen presentation by DC on MHC class II and consequent production of follicular helper T cells. A series of mutant mice were tested to determine the DC subtypes responsible for this MHC II presentation of targeted antigen, compared to presentation of antigen on MHC I. A new clec9A null mouse was developed; these mice did not give enhanced antibody production, confirming the response was dependent on Clec9A-expressing DC. However targeting of antigen to Clec9A in batf3 null mice produced enhanced antibody responses despite the marked reduction in CD8+ DC, the major Clec9A-expressing DC subtype. This was shown to be dependent on efficient MHC II presentation by minor Clec9A-expressing DC subtypes in the environment of the Batf3−/− mice, namely early cells of the CD8 DC lineage and the plasmacytoid-related CD8+ DC subset, but not by plasmacytoid cells themselves. However in normal mice most MHC II presentation of the Clec9A-targeted antigen was by the major CD8+ DC population, the DC also responsible for presentation on MHC I.

Histological and immunohistochemical profile of sporadic and familial medullary thyroid carcinoma

IntroductionThe histological and immunohistochemical profile of medullary thyroid carcinoma is ill-defined. The objective of this study was to determine the epidemiological, histological, and immunohistochemical characteristics of medullary carcinoma and to analyze whether differences exist between sporadic and familial carcinomas. Patients and methodsFifty-five histologically confirmed tumors were studied. Histological slides were reviewed and immunohistochemical staining of the archival paraffin blocks was performed. ResultsNineteen of the 55 carcinomas (35%) were sporadic, and 36 (65%) familial. Sex distribution was similar, but familial carcinoma was more common in patients under 40 years of age (p<0.001). A solid growth pattern and plasmacytoid cells were found in most cases. C-cell hyperplasia and multicentricity were more frequent findings in familial carcinoma, while tumor necrosis, hemorrhagic foci, vascular invasion, and neovascularization were more common in the sporadic type. Immunohistochemical staining was positive for calcitonin, CEA, bcl-2, and p53 protein. With regard to staging, familial carcinomas were diagnosed in the earliest stages, when they were smaller and there were no lymph node metastases (p<0.01). ConclusionsFamilial cases were more frequent when there was more C-cell hyperplasia and multicentricity. Sporadic cases more frequently showed foci of necrosis, hemorrhage, vascular invasion, and neovascularization. Neither histopathological nor immunohistochemical criteria are useful for differentiating between familial and sporadic forms.

Large Neglected Ulcerated Melanoma Mimicking Extramedullary Plasmacytoma

Amelanotic melanoma, a renowned impersonator, has taken on a new persona. A 63-year-old woman was seen in the emergency room with a chief complaint of back pain after a fall and was discovered to have a 15-cm fungating mottled gray mass independent of bone on the right elbow. Initial workup discovered lytic calvarial lesions, anemia (Hb 7; Hct 20%), and circulating plasma cells consistent with plasma cell myeloma. Biopsy of the elbow mass displayed sheets of plasmacytoid cells, some reactive for CD138. Flow cytometry revealed a substantial portion of the plasma cells in the tumor that were kappa restricted consistent with cutaneous plasmacytoma. The elbow mass was initially signed out as extramedullary involvement by her myeloma. Reevaluation of the mass after the patient experienced an explosive growth of multinodular jet black malignant melanoma on ipsilateral breast revealed MART-1 and S-100 reactivity of the majority of the cells. In retrospect, the elbow mass was a neglected primary amelanotic malignant melanoma with neoplastic plasma cells participating in its chronic inflammatory infiltrate.

Perfil histológico e inmuno-histoquímico del carcinoma medular de tiroides esporádico y familiar

Introduction The histological and immunohistochemical profile of medullary thyroid carcinoma is ill-defined. The objective of this study was to determine the epidemiological, histological, and immunohistochemical characteristics of medullary carcinoma and to analyze whether differences exist between sporadic and familial carcinomas. Patients and Methods Fifty-five histologically confirmed tumors were studied. Histological slides were reviewed and immunohistochemical staining of the archival paraffin blocks was performed. Results Nineteen of the 55 carcinomas (35%) were sporadic, and 36 (65%) familial. Sex distribution was similar, but familial carcinoma was more common in patients under 40 years of age (p < 0.001). A solid growth pattern and plasmacytoid cells were found in most cases. C-cell hyperplasia and multicentricity were more frequent findings in familial carcinoma, while tumor necrosis, hemorrhagic foci, vascular invasion, and neovascularization were more common in the sporadic type. Immunohistochemical staining was positive for calcitonin, CEA, bcl-2, and p53 protein. With regard to staging, familial carcinomas were diagnosed in the earliest stages, when they were smaller and there were no lymph node metastases (p < 0.01). Conclusions Familial cases were more frequent when there was more C-cell hyperplasia and multicentricity. Sporadic cases more frequently showed foci of necrosis, hemorrhage, vascular invasion, and neovascularization. Neither histopathological nor immunohistochemical criteria are useful for differentiating between familial and sporadic forms.

Multiple myeloma with primary manifestation in mandibular area

AbstractMultiple myeloma (MM) is a haematological disease characterised by the multicentric proliferation of plasma cells in the bone marrow. This relatively rare disease develops mainly in men (mean age, 60 years). The occurrence of the disease in jaws is uncommon as a primary manifestation. A 73‐year‐old man was first seen with a chief complaint of a painful mandibular enlargement persisting for 1 month with an increase in the volume of the gingiva, which bled during oral hygiene. The Xray revealed a ‘punched‐out’ lesion with ill‐defined margins in the mandibular ramus and body. A computed tomography scan showed a mandibular osteolytic lesion extending to the surrounding soft tissue. The incisional biopsy revealed a monotonous proliferation of plasmacytoid cells strongly immunoreactive to Kappa IgG, which confirmed the diagnosis of MM. After the biopsy, the patient spontaneously fractured his ribs, and the Bence Jones protein test was positive. Conformal radiotherapy followed by bortezomib with melphalan and prednisone was the elected treatment. The patient stopped treatment after two cycles, and progression to death followed after 6 months. This case report reinforces the data on the importance of early diagnosis of MM in the jaw and illustrates the contribution that oral assessment can provide for the diagnosis of this disease.

Leptomeningeal myelomatosis in previously treated high-risk kappa light chain multiple myeloma: case report and literature review

Leptomeningeal myelomatosis in previously treated high-risk kappa light chain multiple myeloma: case report and literature review Maro Ohanian1, James Alaly2, Stephen Samuel3, Christian Cable1, Kathleen Halka11Department of Hematology/Oncology, 2Department of Radiology, 3Department of Hematopathology, Scott and White Healthcare, The Texas A&amp;M Health Science Center College of Medicine, Temple, Texas, USAObjective: To describe leptomeningeal myelomatosis (LM) in previously treated high-risk kappa light chain multiple myeloma (MM) and to review the literature.Case report: A 71-year-old female with previously treated kappa light chain myeloma presented with right lumbosacral discomfort. Magnetic resonance imaging (MRI) of spine revealed multiple intradural masses involving the cauda equina, with mass effect on adjacent nerve roots. Brain MRI was unremarkable. Cerebrospinal fluid flow cytometry confirmed an abnormal population of plasma cells with kappa restriction; CD38, CD138, and CD56 were positive. She was originally diagnosed with kappa light chain myeloma 10 months earlier while hospitalized for anemia, thrombocytopenia, renal failure, and hypercalcemia. Bone marrow revealed plasma cell myeloma approaching 100% cellularity, with 92% plasma cells, atypical plasmacytoid cells with prominent nucleoli, and significant cytogenetic abnormalities: deleted 13, c-myc rearrangements, -X, +1. Treatments consisted of seven cycles of bortezomib with weekly dexamethasone. Her last dose had been 4 months earlier. After treatment, bone marrow demonstrated a complete remission with normal cytogenetics. Her clinical course had otherwise been indolent with a good hematologic response. After diagnosis of LM, therapy included focal external beam radiation to the cauda equina, weekly bortezomib and dexamethasone, intrathecal (IT) cytarabine liposomal every 2 weeks for five doses, and monthly IT cytarabine liposomal thereafter. The cerebrospinal fluid gradually cleared on serial lumbar punctures and follow-up MRI demonstrated near complete resolution of the intradural masses. Five months after diagnosis the patient is essentially asymptomatic.Conclusion: The incidence of central nervous system (CNS) involvement in MM patients is 1%. LM is associated with cytogenetic abnormalities and plasmablastic morphology. It can occur with a seemingly low tumor burden. Novel agents such as bortezomib allow for prolonged survival in high-risk patients; however, with inadequate CNS penetration, complications such as LM may be inevitable.Keywords: leptomeningeal myelomatosis, intrathecal, complete remission

The varied presentation of metastatic melanoma in fine needle aspiration cytology of the breast

To identify cytomorphological patterns of metastatic melanoma (MM) in breast fine needle aspiration (FNA) specimens and highlight the differential diagnoses and features most useful in identifying MM. The clinical, radiological and FNA findings of 16 cases were reviewed. Cytological features evaluated related to cell arrangement, size and shape of cells, nuclear and cytoplasmic features, and the presence or absence of necrosis. The series consisted of 14 females and two males, ranging in age from 24 to 83 years (mean = 50 years). A previous history of melanoma was available in 12/16 (75%) cases at the time of FNA reporting; however the clinical/radiological impression in 4/16 cases was of a breast cyst. The cases were classified into six morphological variants: classical (8/16), pseudopapillary (3/16), spindle-cell (1/16), melanin-rich (1/16), pleomorphic (2/16) and lymphoma-like (1/16). The varying patterns raised a wide range of differential diagnoses; however, discohesion, binucleation and granular cytoplasm were the major features seen in 94% of all cases. In 14/16 cases (88%), plasmacytoid cells, prominent nucleoli and cytoplasmic vacuolation were identified. Melanin and multinucleation were detected in 44% of cases and intranuclear cytoplasmic invaginations in 63%. Necrosis was present in more than half of the cases (56%). MM should be considered in the differential diagnosis of breast FNA specimens when atypical cells are seen that present as plasmacytoid cells in a dispersed or pseudopapillary pattern, or as spindle, pleomorphic or pigmented cells. These features, combined with clinical history and immunocytochemistry, may assist in correctly identifying MM and directing optimal treatment.

Serous fluid cytology of multicentric Castleman’s disease and other lymphoproliferative disorders associated with Kaposi sarcoma‐associated herpes virus: a review with case reports

The aim of this study is to describe and review the cytological features of Kaposi sarcoma-associated herpes virus (KSHV) related entities, such as multicentric Castleman's disease (MCD), plasmablastic-lymphoma (PBL) and primary effusion lymphoma (PEL), which all may present as body cavity effusions. Serous fluid cytology of MCD and PBL has not, to our knowledge, thus far been described. Although different in nature, MCD, PBL and PEL are characterized by similar morphological features. Body cavity effusions from four different patients with previously known or unknown KSHV-related lymphoproliferations have been examined by routine cytology, immunocytochemistry (IC) and polymerase chain reaction (PCR). MCD, PBL and PEL are all characterized by increased cellularity, comprising mainly lymphoid and plasmacytoid cells with variable proportions of immunoblasts. Immunocytochemistry and PCR results show the MCD to be CD138 and KSHV positive, CD30 negative, IgM, IgH and lambda restricted but IgH polyclonal. PBL was CD138 positive, kappa restricted, weakly positive with VS38 and over 80% positive with MIB 1. PEL was CD45, EMA, CD138, KSHV, p53 and CD3 positive, CD20, EBV, CD30, CD2, CD4, ALK1, epithelial and mesothelial markers negative, and PCR monoclonal B-cell expanded (Ig-kappa bands). Cytological examination of effusions in KSHV-related lymphoproliferative disorders may show similar morphological features but clonality studies and immunocytochemistry are very helpful in distinguishing between these rare benign and malignant lymphoproliferative diseases.

Basal cell carcinoma with myoepithelial differentiation: a distinct plasmacytoid cell variant with hyaline inclusions

We describe a 74-year-old man presenting with a 10-year history of an asymptomatic, skin-colored hard plaque on his left cheek. Microscopy revealed well-demarcated tumor with peripheral palisading and peritumoral clefting in the dermis. The tumor included many plasmacytoid cells with cytoplasmic hyaline inclusions and eccentric nuclei. Electron microscopic examination showed that hyaline inclusions consisted of aggregates of filaments. Immunoperoxidase staining showed diffuse cytoplasmic expression of 34bE12, smooth muscle actin, calponin and p63. We diagnosed the patient with basal cell carcinoma (BCC) with myoepithelial differentiation and treated him with excision. Eight months postoperatively, the patient remained well with no recurrence. This distinct variant of BCC with myoepithelial differentiation, showing cytoplasmic hyaline inclusions and eccentric nuclei, has previously been confusingly termed 'signet-ring cell BCC'. However, these plasmacytoid cells differ from signet-ring cells with vacuolated cytoplasm. To avoid confusion, we suggest the designation 'BCC with myoepithelial differentiation'.

Fine needle aspiration cytology of medullary carcinoma of the thyroid with a focus on rare variants: a review of 78 cases

The cytological features of variants of medullary carcinoma of the thyroid (MCT) are sparsely documented in the literature from case reports. Detailed cytomorphological analysis of MCT variants and features helping to distinguish them from usual MCT are presented here. A total of 78 aspirates with a diagnosis of MCT over a period of 10 years were re-evaluated. Cytomorphological details were reviewed and semiquantitatively analysed. Histology slides were reviewed in 36 cases. Most aspirates showed classical features of dispersed polygonal or plasmacytoid cells with areas of spindling. In 54 aspirates, a definite cytological diagnosis of medullary carcinoma was made, which in 87.1% was based on cytomorphology alone and in 12.9% was based on immunocytochemistry for calcitonin. In 30.1% of aspirates from MCT, a guarded report of tumour was given in the absence of calcitonin immunocytochemistry. Of the 78 cases, nuclear grooves were seen in 5.1%, intranuclear cytoplasmic inclusions in 28.2%, cytoplasmic granularity in 23.1% and bizarre cells with abrupt anisocytosis in 85.9%. A follicular arrangement was seen in 14.1% and was more frequent in the follicular type (one case) and mixed follicular and medullary carcinoma (one case). Melanin production was seen in aspirates from two cases. One case of the giant cell type of MCT was seen, in which background cells showed large pleomorphic nuclei and numerous bizarre tumour giant cells, prompting a differential diagnosis with anaplastic carcinoma. One example each of the small cell type, paraganglioma-like MCT and papillary MCT were seen. MCT has uniform cytological features in the majority of aspirates, including many of the histological variants. Searching for pigment in every aspirate of MCT may be rewarding. The giant cell type of MCT is rare and has to be differentiated from anaplastic carcinoma.

Primary leptomeningeal plasmablastic lymphoma

Lymphomas that develop in human immunodeficiency virus (HIV) infected patients are predominantly aggressive B-cells lymphomas. The most common HIV-associated lymphomas include Burkitt lymphoma, diffuse large B-cell lymphoma (that often involves the CNS), primary effusion lymphoma, and plasmablastic lymphoma (PBL). Of these, PBL is relatively uncommon and displays a distinct affinity for presentation in the oral cavity. In this manuscript we report a previously undescribed primary leptomeningeal form of PBL in a patient with acquired immunodeficiency syndrome. A 40-year-old HIV positive man presented with acute onset confusion, emesis, and altered mental status. Lumbar puncture showed numerous nucleated cells with atypical plasmocyte predominance. CSF flowcytometry showed kappa restriction with CD8 and CD38 positivity and negative lymphocyte markers, while the MRI showed diffuse leptomeningeal enhancement. As the extensive systemic work-up failed to reveal any disease outside the brain, an en bloc diagnostic brain and meningeal biopsy was performed. The biopsy specimen showed sheets of plasmacytoid cells with one or more large nuclei, prominent nuclear chromatin, scattered mitoses, and abundant cytoplasm, highly suggestive of plasmablastic lymphoma. HIV-associated malignancies have protean and often confusing presentations, which pose diagnostic difficulties posed to the practicing neurological-surgeons. Even in cases where an infectious cause is suspected for the meningeal enhancement, neoplastic involvement should be considered, and cytology and flow-cytometry should be routinely ordered on the CSF samples.

Plasmacytoid urothelial carcinoma of the urinary bladder: clinicopathologic, immunohistochemical, ultrastructural, and molecular analysis of a case series

A plasmacytoid variant of urothelial carcinoma has been recently recognized in the World Health Organization classification system. This is characterized by a discohesive growth of plasmacytoid cells with eccentric nuclei, extending in the bladder wall and often in the perivesical adipose tissue. Herein, we report the clinicopathologic, immunohistochemical, ultrastructural, and molecular features of a series of plasmacytoid urothelial carcinoma of the urinary bladder. Four bladder carcinomas characterized by epithelial cells with morphologic appearance resembling plasma cells were evaluated at the immunohistochemical, electron microscopic, and molecular genetic levels. Tumor cells stained with cytokeratins, epithelial membrane antigen, GATA-3 (endothelial transcription factor 3), CD15, p53, and p16. In addition, malignant cells strongly stained with CD138 in all the cases, whereas leukocyte common antigen and multiple myeloma 1/interferon regulatory factor 4 were completely negative, nor immunoreactivity was seen for either κ or λ light chains. The electron microscopic examination showed the presence of divergent squamous and glandular differentiation. At variance with conventional urothelial carcinoma, the analysis of exons 4-9 of TP53 gene revealed no alteration in all the 4 tumors tested, and this can be of value in choosing additional chemotherapy after surgery. Plasmacytoid carcinoma of the bladder is a tumor entity, which can be characterized by specific immunohistochemical markers, including positivity for GATA-3, and presents phenotypic and genotypic peculiarities.

Noxa mediates p18INK4c cell-cycle control of homeostasis in B cells and plasma cell precursors

AbstractInhibition of Cdk4/Cdk6 by p18INK4c (p18) is pivotal for generation of noncycling immunoglobulin (Ig)-secreting plasma cells (PCs). In the absence of p18, CD138+ plasmacytoid cells continue to cycle and turnover rapidly, suggesting that p18 controls PC homeostasis. We now show that p18 selectively acts in a rare population of rapidly cycling CD138hi/B220hi intermediate PCs (iPCs). While retaining certain B-cell signatures, iPCs are poised to differentiate to end-stage PCs although the majority undergo apoptosis. p18 is dispensable for the development of the PC transcriptional circuitry, and Blimp-1 and Bcl-6 are expressed fully and mutually exclusively in individual iPCs. However, a minor proportion of iPCs express both, and they are preferentially protected by p18 or Bcl-xL overexpression, consistent with expansion of the iPC pool by Bcl-xL overexpression, or loss of proapoptotic Bim or Noxa. Expression of Noxa is induced during B-cell activation, peaks in iPCs, and selectively repressed by p18. It is required to promote apoptosis of cycling B cells, especially in the absence of p18. These findings define the first physiologic function for Noxa and suggest that by repressing Noxa, induction of G1 arrest by p18 bypasses a homeostatic cell-cycle checkpoint in iPCs for PC differentiation.

Primary effusion lymphoma associated with Human Herpes Virus-8 and Epstein Barr virus in an HIV-infected woman from Kampala, Uganda: a case report

IntroductionPrimary effusion lymphoma is a recently recognized entity of AIDS related non-Hodgkin lymphomas. Despite Africa being greatly affected by the HIV/AIDS pandemic, an extensive MEDLINE/PubMed search failed to find any report of primary effusion lymphoma in sub-Saharan Africa. To our knowledge this is the first report of primary effusion lymphoma in sub-Saharan Africa. We report the clinical, cytomorphologic and immunohistochemical findings of a patient with primary effusion lymphoma.Case presentationA 70-year-old newly diagnosed HIV-positive Ugandan African woman presented with a three-month history of cough, fever, weight loss and drenching night sweats. Three weeks prior to admission she developed right sided chest pain and difficulty in breathing. On examination she had bilateral pleural effusions.Haematoxylin and eosin stained cytologic sections of the formalin-fixed paraffin-embedded cell block made from the pleural fluid were processed in the Department of Pathology, Makerere University, College of Health Sciences, Kampala, Uganda. Immunohistochemistry was done at the Institute of Haematology and Oncology "L and A Seragnoli", Bologna University School of Medicine, Bologna, Italy, using alkaline phosphatase anti-alkaline phosphatase method. In situ hybridization was used for detection of Epstein-Barr virus.The tumor cells were CD45+, CD30+, CD38+, HHV-8 LANA-1+; but were negative for CD3-, CD20-, CD19-, and CD79a- and EBV RNA+ on in situ hybridization. CD138 and Ki-67 were not evaluable. Our patient tested HIV positive and her CD4 cell count was 127/μL.ConclusionsA definitive diagnosis of primary effusion lymphoma rests on finding a proliferation of large immunoblastic, plasmacytoid and anaplastic cells; HHV-8 in the tumor cells, an immunophenotype that is CD45+, pan B-cell marker negative and lymphocyte activated marker positive. It is essential for clinicians and pathologists to have a high index of suspicion of primary effusion lymphoma when handling HIV positive patients who have effusions without palpable tumor masses. Basic immunohistochemistry is essential for definitive diagnosis.

Methotrexate-associated lymphoplasmacytic lymphoma complicated with type 2 cryoglobulinemia

A 62-year-old female suffering from rheumatoid arthritis(RA) for 16 years was referred to our hospital with out ofbreath on slight exertion. She had been prescribed withmethotrexate (MTX; 4 mg per week) and prednisolone for10 years for the treatment of RA. Upon physical exami-nation, tender liver and spleen that extended below thexiphoid were palpable with a protuberant abdomen. Com-puted tomography (CT) showed hepatosplenomegaly,bilateral pleural effusions and ascites in the absence of lungfield abnormalities or lymphadenopathy. Bone marrowexamination was performed to demonstrate an infiltrationof clonal B cells confirmed by immunocytological analysiswith flow cytometry. She was diagnosed as having MTX-associated lymphoproliferative disorder (LPD). The effu-sions in the body cavities and hepatosplenomegaly weredramatically improved only with the withdrawal of MTX.She had been asymptomatic for 2 years until the currenthospitalization. She presented herself in the outpatientdepartmentwithacomplaintofheadache,vertigoandlossofvisionandthenshewasreadmittedbecauseofextensivefluidretention in the chest, abdomen and lower extremities. A CTscan showed recurrence of the massive effusions in the bodycavities and hepatosplenomegaly (Fig. 1a). Histologicalanalysis for the liver specimen obtained by an ultrasound-guided needle biopsy showed a typical relatively monoto-nousappearanceoflymphocytes,plasmacytoidlymphocytesand plasma cells (Fig. 1b). Proliferating cells were stronglyexpressedwithCD20(Fig. 1c).Immunocytologicalanalysiswith flow cytometry demonstrated that the atypical lym-phocytes were positive for CD19, CD20 surface moleculeswith jlight chain-restricted surface immunoglobulin (Ig)-Mand negative for CD5, CD10 and CD23 surface molecules.Bone marrow examination showed a lymphoplasmacyticinfiltrate composed of lymphocytes with basophilic cyto-plasm and plasmacytoid cells (Fig. 1d). Laboratory studieswere remarkable for a white blood cell (WBC) of 2.8 910

Lymph Node Lesion of Acute Infectious Mononucleosis in the Elderly : A Case Report

We present here lymph node lesion of infectious mononucleosis (IM) in an elderly patient. An 80-year-old Japanese woman presented with a 1 month history of left supraclavicular lymphadenopathy accompanied by high-grade fever, general fatigue and swelling in the bilateral submandibular gland region. Physical examination on admission demonstrated systemic lymphadenopathy up to 40 mm in diameter. The hemoglobin was 12.0 g/dL, white blood cell count 10.5 × 10/L (atypical lymphocytes 25%) (Fig. 1a) and platelet count 205 × 10/L. Serum protein electrophoresis demonstrated a polyclonal hyper-gglobulinemia. Measurement of serum immunoglobulin (Ig) levels demonstrated the following : IgG 4,856 mg/dL, IgA 707 mg/dL and IgM 314 mg/dL. Subsequent serologic tests for Epstein-Barr virus (EBV) showed a previous infection pattern : a viral capsid antigen (VCA) IgG titer of 4.5 (< 0.5 mg/dL), a VCA IgM titer of 0.0 (< 0.5 mg/dL), an early antigen (EA) IgG titer of 0.2 (< 0.5 mg/dL), and an EBV nuclear antigen (EBNA) titer of 1.5 (< 0.5 mg/dL). However, abnormal high titer of EBVDNA (7.6 × 10 ; normal range < 2.0 × 10) was detected in peripheral blood. Cervical lymph node biopsy was performed. Information from flow cytometry of the biopsied specimens showed a polyclonal B cell population. There was no absence of panT-cell markers. The patient treated with prednisolone, and she is currently alive without disease 14 months after disease onset. Tissue specimens were fixed in formalin solution, routinely processed and embedded in paraffin. For light microscopic examination, the sections were stained with hematoxylin-eosin (HE). Immunohistochemical studies were performed using the antigen retrieval method on the Histofine Histostainer (Nichirei Bioscience Inc, Tokyo, Japan) according to the manufacturer’s instructions. The panel of antibodies included, human immunoglobulin light chains (k and l), SP7 (CD3), 4C7 (CD5), L26 (CD20), MCS-1 (CD15), and CD30 (1G12) (Nichirei). Sections with known reactivity for antibodies assayed served as positive controls and sections treated with normal rabbit and mouse serum served as negative controls. In situ hybridization (ISH) with EBV-encoded small RNA (EBER) oligonucleotides was also performed to test for the presence of EBV small RNA in formalin-fixed paraffinembedded sections using the hybridization kit (Dako A/S, Glostrup, Denmark). DNA was extracted from paraffin-embedded sections. The variable region (CDR2 and FW3) and VDJ region (CDR3) of immunoglobulin heavy chain (IgH) gene were amplified by semi-nested PCR, using primers of FR2B, LJH and VLJH, according to a previously described method. Primers were as follows: 5’-CCGG (A/G) AA (A/G) (A/G) GTCTGGAGTGG-3’, as upstream consensus V region primer (FR2B) ; 5’-TGAGGAGACGGTGACC-3’, as a consensus J region primer (LJH) ; 5’-GTGACCAGGGT [A/C/G/T] CCTTGGCCCCAG-3’, as a consensus J region primer (VLJH). PCR products were estimated to be about 200-300 bps in length. Histologically, on low power field, the biopsied specimens demonstrated numerous lymphoid follicles with normal or atrophic germinal centers and interfollicular widening (Fig. 1b). Marked proliferation of arborizing vessels was noted in the interfollicular area (Fig. 1b). The lymphoid sinuses occasionally appeared to be compressed by the paracortical expansion. The paracortical area and medullary cords were heavily infiltrated with small and medium-sized lymphocytes, mature plasma cells, plasmacytoid cells, immature plasma cells, im-

Fine needle aspiration cytology of solid neuroendocrine carcinoma of the breast: A case report

We report a case of neuroendcrine (NE) carcinoma in the right breast of a 67-year-old female, ultrasonography revealed a lesion composed of irregular hypoechoic masses and mammography showed asymmetric breast tissue. Histopathologic examination of the surgical sample showed a solid to nested proliferation of plasmacytoid cells that showed immunocytochemical positivity for chromogranin A, synaptophysin, CD56, and estrogen receptor. Our case was diagnosed as solid NE carcinoma. Though the findings of fine needle aspiration cytology reflected the histological features, we were not able to cytopathologic grounds only to predict the NE nature of this tumor. We performed immunocytochemistry using Chromogranin A, Synaptophysin, and CD56 on our cytologic smear retrospectively with positive results for all of the markers. When the cytopathologic examination of a given breast neoplasm is suggestive of NE differentiation, immunocytochemical staining for NE markers is generally useful for a correct preoperative diagnosis. An acurate preoperative diagnosis of NE carcinoma on FNAC can be achieved based on its distinctive cytomorphologic and immunocytochemical features.

Primary CNS plasmablastic lymphoma: Report of a case with CSF cytology, flow cytometry, radiology, histological correlation, and review of the literature

Plasmablastic lymphoma (PBL) is a rare subtype of diffuse large B cell lymphoma and commonly presents as an oral mass in HIV patients. Extraoral PBL has been reported, including one case of primary central nervous system PBL (PCNSPBL). The cytological features of PBL have been described, including cerebrospinal fluid (CSF) cytology findings for secondary CNS involvement by PBL. The etiology of PCNSPBL is still unknown. We report here the CSF cytology of a PCNSPBL, which shows a hypercellular specimen composed of markedly atypical, singly dispersed plasmacytoid cells with frequent abnormal mitoses and binucleation. The neoplastic cells are positive for CD138. Flow cytometry of the CSF specimen demonstrates a monoclonal neoplastic cell population, which is CD138 positive, kappa light chain positive, lambda light chain negative, and CD19 negative. Molecular analysis and immunohistochemical stains on a tissue biopsy confirmed the diagnosis and reveal concurrent infections with Epstein-Barr virus and human polyomavirus JC virus. Clinical and radiological correlations are reported, and the literature is reviewed. To the best of our knowledge, this is the first case report for CSF cytology of a PCNSPBL, demonstrating the utility of the cytological examination in the triage and diagnosis of this disease. Because of its dismal prognosis, it is critical for cytopathologists to be aware of the entity and recognize the neoplastic cells in CSF specimen. This report also emphasizes the importance of clinical and radiological correlation in the diagnosis of this lethal disease.

IgG-associated immune thrombocytopenia in Waldenström macroglobulinemia

Waldenström macroglobulinemia (WM) is characterized by serum IgM monoclonal gammopathy, and only occasionally complicated by immune thrombocytopenia. Rarely, coexistence of non-IgM gammopathy in WM has been reported. Herein, we describe an 81-year-old case of WM with rapidly progressive immune thrombocytopenia accompanied by concurrent IgG gammopathy and elevation of platelet-associated IgG (PA-IgG). Immunostaining of the bone marrow specimen displayed not only IgM positive but also IgG positive plasmacytoid cells. Although dexamethasone therapy had no effect on thrombocytopenia, a modified RCD regimen (rituximab 375 mg/m(2) i.v. day 1, cyclophosphamide 375 mg/m(2) i.v. day 2 and dexamethasone 12 mg/body orally days 1-7) successfully normalized PA-IgG as well as IgG and IgM paraproteinemia and significantly increased platelet count. The current case suggests that the IgG gammopathy associated with WM is likely to be an etiology of immune thrombocytopenia and that tumor reduction, rather than immunosuppression, leads to an improvement of concurrent thrombocytopenia.

Primary mucinous carcinoma of the skin with plasmacytoid cells

Primary mucinous carcinoma of the skin with plasmacytoid cells