Pulmonary crystal‐storing histiocytosis diagnosed by computed tomography‐guided fine‐needle aspiration

Crystal‐storing histiocytosis (CSH) is a rare process most often occurring in conjunction with an underlying hematopoietic neoplasm, usually multiple myeloma or low‐grade B‐cell lymphoma. We report the first case of pulmonary CSH diagnosed by fine‐needle aspiration biopsy. A patient with a history of urothelial carcinoma developed a lung nodule, which was evaluated by fine‐needle aspiration biopsy. Cytologic examination revealed macrophages with abundant cytoplasmic crystals diagnostic of CSH. Based on this cytologic interpretation, additional clinical laboratory evaluation was pursued and revealed a previously unknown monoclonal serum protein. CSH must be differentiated from other non‐neoplastic and neoplastic lesions and when diagnosed, should trigger a search for an underlying lymphoproliferative disorder. Diagn. Cytopathol. 2010. © 2009 Wiley‐Liss, Inc.     

KRAS testing on colo‐rectal carcinoma cytological imprints

Anti‐EGFR monoclonal antibodies, cetuximab, and panitumumab, are administrated under the condition that advanced colo‐rectal cancer (CRC) carries a wild‐type KRAS gene. Thus, clinicians request pathologists to genotype KRAS before treatment. In the near future routine mutation testing at the same time of the surgery may be implemented. The reliability of a rapid KRAS testing on ex vivo cytological samples obtained by direct scraping of the colon tumour tissue is here evaluated. A consecutive series of 20 surgically resected, primary CRC specimens was analysed. Fresh tissue from CRC was scraped with a scalpel blade, smeared on uncoated glass slides, air‐dried and Diff–Quik stained to ensure malignant cell presence. The same tissue area was also histologically processed. Exon 2 KRAS gene mutations were evaluated on both cytological and histological specimens by dideoxy sequencing and by the DxS KRAS Mutation Test Kit (DxS, Manchester, England). Data obtained on on imprint cytology and matched histological samples showed full concordance; however, the mutation frequency was slightly higher (35%) by the DxS KRAS Mutation Test Kit than by the dideoxy sequencing (30%). Thus, colon cancer imprint cytology sample is a reliable biospecimen for both dideoxy‐sequencing and DxS KRAS Mutation Test Kit analysis and it may be useful to abbreviate the KRAS assay turnaround time. Diagn. Cytopathol. 2011;39:274–277. ©2010 Wiley‐Liss, Inc.     

Thymic mucosa‐associated lymphoid tissue lymphoma with immunoglobulin‐storing histiocytosis in Sjögren's syndrome

Mucosa‐associated lymphoid tissue (MALT) lymphoma arising from the thymus is extremely rare. Only 33 cases of thymic MALT lymphoma have been reported to date. We present the case of a 53‐year‐old Japanese woman with Sjögren's syndrome who was diagnosed with thymic MALT lymphoma. In addition, the patient had the characteristic clinical and pathological features of thymic MALT lymphoma, as found in most of the 33 previous cases, except that there was an immunoglobulin G (IgG) phenotype, i.e. Sjögren's syndrome, epithelial cysts, lymphoepithelial lesions, and marked plasmacytic differentiation. The serum IgA levels were also elevated with IgA kappa M protein. This hypergammaglobulinemia remained unchanged after operation. The serological abnormalities may not arise from MALT lymphoma itself and may arise from the immune system hyper‐reactivity evoked by Sjögren's syndrome. Of further interest were marked accumulations of CD68‐positive histiocytes containing abundant eosinophilic globular inclusions in their cytoplasm. These inclusions were immunopositive for IgG‐kappa, suggesting immunoglobulin inclusion bodies. The globular immunoglobulin inclusion bodies have been reported in non‐crystallized immunoglobulin‐storing histiocytosis in only one patient with multiple myeloma. To our knowledge, this is the first case of thymic MALT lymphoma with marked accumulation of histiocytes with immunoglobulin inclusions in a patient with Sjögren's syndrome.     

FNA diagnosis of primary adult onset lymphocutaneous Langerhans' cell histiocytosis masquerading as deep fungal mycosis

Langerhans' cell histiocytosis (LCH) in its aggressive disseminated form seen most often in children is easily diagnosed by the treating physician. On the contrary, LCH in an adult is localized, extremely rare, and, hence, its diagnosis is missed quite often or underdiagnosed. We describe the troubleshooters encountered in the fine-needle aspiration (FNA) diagnosis of LCH in an adult who presented for 4 years with ulceronodular lesions over the neck, both axillae, and inguinal regions since 4 years of age, which had closely mimicked deep mycosis both clinically and histopathologically.     

Fine-needle aspiration cytology of sinus histiocytosis with massive lymphadenopathy: A case report

Cytological findings of sinus histiocytosis with massive lymphadenopathy (SHML), involving bilateral cervical lymph nodes of a 12-yr-old boy, are presented here. A striking feature was the presence of large histiocytes with abundant pale cytoplasm containing well-preserved lymphocytes, plasma cells, and occasional neutrophils, scattered in a background of reactive lymphoid cells. Subsequent open biopsy of the lymph node mass confirmed the cytologic findings. Cytologic features of SHML are virtually diagnostic and can negate the need for an open biopsy in most cases. Diagn Cytopathol 1996;15:221–223. © 1996 Wiley-Liss, Inc.     

Fine-needle aspiration cytology in a case of isolated involvement of thyroid with Langerhans cell histiocytosis

We present an unusual case of isolated thyroid involvement with Langerhans cell histiocytosis (LCH), diagnosed presumptively by fine-needle aspiration (FNA) cytology and subsequently confirmed by immunohistochemistry in a 13-yr-old boy. The cytologic findings include high cellularity in a hemorrhagic background, the presence of characteristic mononucleated and multinucleated Langerhans cells with prominent nuclear grooves, and abundant foamy cytoplasm in a background of mixed eosinophilic and lymphocytic infiltrate, along with the presence of few focal aggregates of benign thyroid follicular cells. Further diagnostic confirmation was obtained by positive S-100 protein immunohistochemistry of the Langerhans histiocytes on paraffin-embedded sections of open thyroid biopsy of the prominently enlarged left lobe. We present the complete clinicopathologic features of this case, along with ultrasound, computerized axial tomographic, and technetium-99 scan findings. We also discuss possible differential diagnostic consideration in light of a review of the literature and the role of FNA cytologic diagnosis in such a rare yet cytomorphologically characteristic case. Diagn. Cytopathol. 1998;19:33–37. © 1998 Wiley-Liss, Inc.     

A case of Langerhans' cell histiocytosis associated with Hodgkin's lymphoma: Fine‐needle aspiration cytologic and histopathological features

Langerhans cell histiocytosis (LCH) can be associated with a variety of malignant neoplasms, the most common being malignant lymphoma, especially Hodgkin's lymphoma (HL). In this report, we describe the fine needle aspiration (FNA) cytologic features of a case with concurrent LCH and HL in a lymph node. A 20‐year‐old man presented with an enlarged left upper cervical lymph node. FNA smears from the swelling revealed numerous CD1a+ and S‐100+ Langerhans‐type cells (LCs) along with many eosinophils, neutrophils, and lymphocytes; there were also large atypical cells with enlarged nuclei having prominent nucleoli. The cytodiagnosis was LCH and the possibility of association with or trans‐differentiation into a lymphoma was suggested. The histopathological diagnosis of the excised left cervical lymph node was classical HL‐nodular sclerosis type (CHL‐NS) with LCH. The lacunar type Reed‐Sternberg (RS) cells were positive for CD30 and CD15, and the LCs were positive for CD1a and S‐100 protein. PET/CT imaging demonstrated hypermetabolic lymph nodes in neck, abdomen, thorax and pelvis as well as pulmonary nodules and a splenic mass. The patient received 13 courses of chemotherapy and two years later, the enhanced CT revealed regressive course of the disease. Diagn. Cytopathol. 2016;44:128–132. © 2015 Wiley Periodicals, Inc.     

Fulminant parvovirus B19‐associated pancarditis with haemophagocytic lympho‐histiocytosis in an immunocompetent adult

Myocarditis is a common cardiac disease that is identified on routine postmortem examinations. Initially, coxsackie viruses, other enteroviruses and adenoviruses were thought to be more common causes of myocarditis; however, recently, parvovirus B19 (PVB19) as well as human herpesvirus 6 (HHV6) have entered the arena. We describe autopsy findings of a patient who had a lethal myocarditis with haemophagocytic lympho‐histiocytosis in a course of systemic PVB19 infection. The present case illustrates the unusually severe and rapid course of PVB19 myocarditis with associated haemophagocytic lympho‐histiocytosis leading to death.     

Role of touch imprint and core biopsy for detection of tumor metastases in bone marrow

A total number of 248 bone marrow trephine biopsies were reviewed and 21 paired biopsies and touch imprints were identified to estimate the role of these two diagnostic methods for detection of tumor metastases from nonhematologic malignancies in the bone marrow. The study period ran between January 1, 1993, and June 1, 1996. Eight histology sections and eight touch imprints were prepared from every case and were reviewed by two pathologists independently. In 20 cases, tumor cells were present without a doubt both on cytologic and histologic preparations. In one touch imprint, single cells were suspicious for malignancy, and the final pathology report was prepared after examination of the histologic sections. There was no positive biopsy in which the imprint was negative for tumor cells, and no positive touch imprint in which the biopsy was negative for such a cells. The results from our study show that every one of these approaches has advantages and disadvantages and that they have a complementary role for identification of solid malignancies in the bone marrow. Diagn. Cytopathol. 1998;18:323–324. © 1998 Wiley-Liss, Inc.     

Eosinophilic granuloma of lymph nodes—a variant of histiocytosis X

A clinicopathologic study of histiocytosis X in lymph nodes disclosed a special variant: primary eosinophilic granuloma of lymph nodes. This variant involves one or more lymph nodes, but does not infiltrate any other organs. Histologically, the infiltration of lymph nodes by histiocytosis X cells and eosinophils is similar to that seen in disseminated or metastatic histiocytosis X. Most cases of eosinophilic granuloma of lymph nodes are recognizable as primary, however, by the heavy infiltration of the surrounding tissue. The predominant proliferating cells are histiocytosis X cells ('Langerhans cells'), which contain Birbeck granules on electron microscopy and are lysozyme-negative. The disease was found in 30 patients among a total of 64 cases of histiocytosis X collected at the Lymph Node Registry in Kiel. Primary eosinophilic granuloma of lymph nodes occurs predominantly in children and young adults and shows a slight preponderance of males. Clinically, the patients present with mostly afcbrile and sometimes painful lymphadenopathy, which is more often solitary (in the cervical or inguinal region) than widespread. The erythrocyte sedimentation rate and/or serum α₂-globulin level are elevated in many patients. There may also be an increase in the number of leucocytes, especially eosinophils, in the blood. The prognosis is favourable: the lymphadenopathy disappeared spontaneously in most patients and only one patient developed two recurrences. Thus, primary eosophilic granuloma of lymph nodes is interpreted as a benign lesion. It might be a special reaction of the T cell system.     

Generalized crystal-storing histiocytosis as a presentation of multiple myeloma: a case with a possible pro-aggregation defect in the immunoglobulin heavy chain

Crystal-storing histiocytosis (CSH) with massive accumulation of particulate immunoglobulins is a rare phenomenon accompanying B-cell dyscrasias. In the reported case (M51), the disease presented as systemic CSH and later was proved to be a frank multiple myeloma. The aggregates of crystal-laden histiocytes were demonstrated in the bone marrow, lungs, kidney, and liver. Additionally, the crystalline immunoglobulin particles were identified in renal stromal cells and in hepatocytes. The patient developed lung adenocarcinoma and died 12 months after the presentation, shortly after the lobectomy. In this paper, we report the results of morphological (including electron microscopy), immunohistochemical, and biochemical analysis. The tendency for aggregation of the IgG kappa monoclonal protein was due to the abnormal physicochemical properties of its heavy chain. Massive accumulation of crystal-storing histiocytes surpassed the myeloma tumor burden and markedly contributed to the severity of the disease.     

Significance of bone marrow fibrosis in multiple myeloma

AIMS: The aim of the current study was to asses the frequency of increased fibrosis in myeloma and to find its correlation with other bone marrow parameters and survival. METHODS: Forty-four multiple myeloma patients diagnosed between 2001 and 2005 were included in the present study. A detailed study of the bone marrow aspiration smears and trephine biopsy was done. Bone marrow fibrosis was graded and correlated with other parameters like plasma cell morphology, pattern of infiltration, mitotic activity and also with the survival of the patients. RESULTS: Increased fibrosis was seen in nine cases (20.5%). It was observed that plasma cell burden in the marrow was under-estimated in the aspirate smears compared with the trephine biopsy in patients with increased fibrosis. Increased marrow fibrosis correlated significantly with poorly differentiated plasma cell morphology (p = 0.020) and mitotic activity (p = 0.003), which by themselves are established prognostic markers for survival in multiple myeloma. Patients with increased fibrosis of the marrow also had a median survival time of just 11 months. CONCLUSIONS: A bone marrow trephine biopsy is essential in all cases of myeloma at diagnosis, as it helps identify a subset of myeloma patients with increased marrow fibrosis and poorer prognosis.