Hansen's disease (leprosy). Diagnosis by aspiration biopsy of lymph nodes

A 61-year-old male native of Mexico presented with generalized enlargement of lymph nodes. Fine needle aspiration (FNA) biopsy established lepromatous leprosy as the cause of the lymphadenopathy. The cytologic findings included abundant, frequently multinucleated histiocytes (globus cells), the cytoplasm of which showed multiple vacuoles; cytoplasmic membrane-bound vacuoles were seen free in the background. The vacuoles contained large numbers of acid-fast bacilli. Globus cells, while characteristic, are not specific for Mycobacterium leprae infection and are seen in certain atypical mycobacterioses in immunodeficient patients. This appears to be the first report of lymphadenopathy due to lepromatous leprosy in which the diagnosis was made by FNA biopsy. The immunologic spectrum of leprosy is correlated with clinical and pathologic findings, and the need to remember infectious processes in evaluating lymphadenopathy and the value of reserving air-dried and alcohol-fixed smears for special stains are emphasized.     

Fine needle aspiration cytologic diagnosis of erythema nodosum leprosum: a case report

BACKGROUND: Erythema nodosum leprosum (ENL), the type 2 lepra reaction occurring in lepromatous or borderline lepromatous leprosy, presents clinically with acute manifestations that compel the patient to seek medical attention. Recognition and timely management of these patients is critical in order to avoid permanent disability. Fine needle aspiration cytology (FNAC) is a simple, effective tool that aids in correct diagnosis and management of ENL. CASE: A 30-year-old woman presented with history of fever, reddening of the face, and multiple raised, reddish, painful swellings of the bilateral forearms and legs for 7 days. One year previously, she was diagnosed and treated for lepromatous leprosy with type 2 reaction. After a thorough clinical examination a diagnosis of ENL was made. FNA smears from the forearm swellings showed pus-like material with intact and degenerated polymorphonuclear leukocytes and many foamy macrophages with strong granular acid-fast bacillus (AFB) positivity. A cytologic diagnosis of ENL was given, which was confirmed on histopathologic examination of skin biopsy. CONCLUSION: Cytologic features such as a large number of intact and degenerated neutrophils with foamy macrophages and strong granular AFB positivity, in an appropriate clinical background, allows a confident diagnosis of ENL.     

Fine needle aspiration cytology in systemic lupus erythematosus lymphadenopathy. A case report

BACKGROUND: Systemic lupus erythematosus (SLE) is an autoimmune disease of unknown etiology characterized by inflammation in various organ systems, including lymph nodes, due to the production of antinuclear antibodies. The onset of disease is between ages 13 and 40 years, with a female preponderance. CASE: A 30-year-old female presented with right cervical lymphadenopathy and gave a history of intermittent fever and swollen joints of 2.5 years' duration. The patient was on intermittent corticosteroids. With a suggestion of tuberculous lymphadenitis, the patient underwent fine needle aspiration (FNA). The diagnosis of lupus adenopathy was established by FNA of enlarged right cervical lymph nodes. Smears showed predominantly typical and atypical immunoblasts, plasma cells, occasional Reed-Sternberg-like cells and dispersed hematoxylin bodies. Smears were negative for acid-fast bacilli. CONCLUSION: When SLE patients develop lymphadenopathy, FNA cytology helps differentiate lupus adenopathy from infectious conditions, such as tuberculous adenitis, and from Kikuchi's lymphadenitis.     

Disseminated histoplasmosis diagnosed by percutaneous needle biopsy of a retroperitoneal lymph node. A case report.

A case of disseminated histoplasmosis diagnosed by percutaneous needle biopsy cytology is reported. The patient presented with fever and pancytopenia. Computed tomography (CT) revealed retroperitoneal lymphadenopathy. Cytology smears prepared from a CT-guided screw needle biopsy of one of the lymph nodes showed numerous histiocytes with intracytoplasmic yeast forms consistent with Histoplasma capsulatum. Fungal cultures prepared from additional needle biopsy material confirmed the diagnosis. This case illustrates the utility of needle biopsy in the evaluation of radiographically detected retroperitoneal lymphadenopathy and in the rapid diagnosis of infectious disease in certain clinical settings.     

Use of fine needle aspiration cytology in leprotic lesions: a report of 4 cases

BACKGROUND: Although a few studies have shown fine needle aspiration cytology (FNAC) to be a sensitive diagnostic tool in the detection of nerve involvement, its role as an initial diagnostic procedure in pure neuritic leprosy (PNL) and in the detection of skeletal lesions with unusual findings has not been documented before. CASES: Three patients who presented with thickened nerves and a fourth with biopsy-proven lepromatous leprosy with lesions in hand bones underwent FNAC. Of the 3 patients with nerve thickening, 2 had a clinical suspicion or diagnosis of neuritic leprosy, whereas in the third patient a clinical differential diagnosis of a soft tissue tumor or parasitic cyst was considered. FNAC in all 3 cases revealed epithelioid cell granulomas, Langhans giant cells and caseous necrosis. Fites and Ziehl-Neelsen stains were negative for acid-fast bacilli. Cytologic diagnosis of pure neuritic leprosy was made in all 3 cases and confirmed by histopathologic examination. FNAC of skeletal lesions from the fourth patient confirmed involvement of bone with unusual cytologic findings of epithelioid cell granulomas and giant cells along with a significant proportion of foamy macrophages and strong Fites stain positivity. CONCLUSION: FNAC is a simple, useful, minimally traumatic and routinely applicable procedure in the diagnosis of pure neuritic leprosy and leprous osteitis.     

Rosai-Dorfman disease manifesting as multiple subcutaneous nodules. Report of a case with diagnosis on a fine needle aspirate

BACKGROUND: Rosai-Dorfman disease (RDD), or sinus histiocytosis with massive lymphadenopathy, is a benign, self-limiting histiocytic proliferative disorder commonly involving the lymph nodes. Extranodal disease occurs in about 40% of cases, and the sites involved are skin, nasal cavity, paranasal sinuses, eyelids, orbit, bone and central nervous system. CASE: A case of RDD presented as subcutaneous nodules and was diagnosed on a fine needle aspirate. The aspirate revealed numerous histiocytes with phagocytosis of lymphocytes, plasma cells and neutrophils. Surgical biopsy and immunocytochemical stain for S-100 protein confirmed the diagnosis. Later the patient developed lymphadenopathy and involvement of the nasal septum. CONCLUSION: Extranodal RDD can be diagnosed by FNAC in conjunction with immunocytochemistry.     

Carcinoma and multiple lymphomas in one patient: establishing the diagnoses and analyzing risk factors

Multiple malignancies may occur in the same patient, and a few reports describe cases with multiple hematologic and non-hematologic neoplasms. We report the case of a patient who showed the sequential occurrence of four different lymphoid neoplasms together with a squamous cell carcinoma of the lung. A 62-year-old man with adenopathy was admitted to the hospital, and lymph node biopsy was positive for low-grade follicular lymphoma. He achieved a partial remission with chemotherapy. Two years later, a PET-CT scan showed a left hilar mass in the lung; biopsy showed a squamous cell carcinoma. Simultaneously, he was diagnosed with diffuse large B cell lymphoma in a neck lymph node; after chemo- and radiotherapy, he achieved a complete response. A restaging PET-CT scan 2 years later revealed a retroperitoneal nodule, and biopsy again showed a low-grade follicular lymphoma, while a biopsy of a cutaneous scalp lesion showed a CD30-positive peripheral T cell lymphoma. After some months, a liver biopsy and a right cervical lymph node biopsy showed a CD30-positive peripheral T cell lymphoma consistent with anaplastic lymphoma kinase-negative anaplastic large cell lymphoma. Flow cytometry and cytogenetic and molecular genetic analysis performed at diagnosis and during the patient’s follow-up confirmed the presence of two clonally distinct B cell lymphomas, while the two T cell neoplasms were confirmed to be clonally related. We discuss the relationship between multiple neoplasms occurring in the same patient and the various possible risk factors involved in their development.     

Esophageal tuberculosis. Endoscopic cytology as a diagnostic tool

OBJECTIVE: To study the utility of endoscopic cytology in the diagnosis of esophageal tuberculosis in clinically unsuspected cases. STUDY DESIGN: During a period of four years, endoscopic cytology of esophageal lesions was performed on 228 patients. In eight (3.5%) the cytologic diagnosis of esophageal tuberculosis was suggested on smears. Upon endoscopic examination, the sites of involvement were mid esophagus (five cases), upper esophagus (two cases) and lower esophagus (one case). Linear ulcer was seen in six cases; growth and narrowing of the lumen were seen in one case each. Endoscopic brush smears in seven cases and fine needle aspiration cytology smear in one case were collected. Air-dried smears stained by Giemsa stain were reviewed for detailed cytologic assessment. RESULTS: Smears showed well-defined granulomas with necrosis in five cases and granulomas without necrosis in three. Cytologic evidence of concurrent poorly differentiated squamous cell carcinoma was observed in one case. Tubercle bacilli were demonstrated in five cases. Endoscopic biopsy showed granulomas in three cases and tubercle bacilli in one case. In six cases there was no clinical or radiologic evidence of tuberculosis at other sites, thereby suggesting the possibility of primary esophageal tuberculosis. The remaining two cases had a past history of tuberculosis; one presented with cervical lymphadenopathy and one mediastinal lymphadenopathy. All patients received antitubercular treatment, and the patient with concurrent malignancy also received radiotherapy. All but one of the patients who succumbed to aspiration pneumonia responded to treatment. CONCLUSION: Endoscopic cytology is a useful modality in the diagnosis of esophageal tuberculosis in clinically unsuspected cases.     

Association of Epstein-Barr virus with an angioimmunoblastic lymphadenopathy-like lymphoproliferative syndrome

A patient presented with fever, night sweats, generalized lymphadenopathy, cold agglutinin hemolytic anemia, and thrombocytopenia. Lymph node biopsy revealed a lymphoplasmacytic infiltrate sparing the cortical sinuses but associated with arborizing blood vessels. Epstein-Barr virus (EBV) DNA was demonstrated in tissue from an involved lymph node. These data suggest an association of EBV with a lymphoproliferative process that resembles angioimmunoblastic lymphadenopathy with dysproteinemia.     

Granulomatous reactivation during the course of a leprosy infection: reaction or relapse

Background

Leprosy is a chronic granulomatous infectious disease and is still endemic in many parts of the world. It causes disabilities which are the consequence of nerve damage. This damage is in most cases the result of immunological reactions.

Objectives

To investigate the differences between a type 1 leprosy (reversal) reaction and relapse on using histopathology.

Methods

The histopathological changes in 167 biopsies from 66 leprosy patients were studied. The patients were selected when their sequential biopsies demonstrated either different patterns or maintained the same pattern of granulomatous reaction over more than two years during or after the treatment of leprosy.

Results

In 57 of the patients studied, a reactivation was seen which coincided with a decrease in the bacteriological index (BI), suggesting that this reactivation (reversal reaction or type 1 leprosy reaction) coincides with an effective capacity for bacteriological clearance. In nine patients, an increase of the bacteriologic index (IB) or persistence of solid bacilli occurred during the reactivation, indicating proliferative activity, suggestive of a relapse. The histopathological aspects of the granulomas were similar in both groups.

Conclusion

Bacterioscopy provided the only means to differentiate a reversal reaction from a relapse in patients with granulomatous reactivation. The type 1 leprosy reaction may be considered as a part effective immune reconstitution (reversal, upgrading reaction) or as a mere hypersensitivity reaction (downgrading reaction) in a relapse.     

Multilobated large B-cell lymphoma diagnosed cytologically. A case report.

BACKGROUND: Fine needle aspiration (FNA) biopsy can be used to reliably classify most conditions involving lymph nodes or, at least, significantly reduce the differential diagnosis. CASE: A 70-year-old male presented with an ulcerated mass arising from the left tonsillar fossa and involving the anterior and posterior pillars. A biopsy of the tonsillar mass performed at an outside hospital was interpreted as a large cell undifferentiated carcinoma. Subsequently the patient developed systemic lymphadenopathy. A bone scan showed intense uptake within the medial tibial plateau of the left knee. FNA biopsy of the right axillary mass was interpreted at University of Cincinnati Medical College as a large cell lymphoma, multilobated type. Histologic and immunohistochemical studies of the lymph node confirmed the presence of multilobated B-cell lymphoma. Lymphoma chemotherapy was initially successful but was discontinued due to toxicity. The patient died two months after the initial cytologic diagnosis of lymphoma. CONCLUSION: Multilobated lymphomas are an unusual variant of non-Hodgkin's lymphomas (mostly B-cell type). Cytology and immunocytochemistry are useful diagnostic procedures that can help to diagnose this relatively uncommon type of lymphoma and significantly reduce the possibility of misdiagnosis.     

Evaluation of qPCR-based assays for leprosy diagnosis directly in clinical specimens

The increased reliability and efficiency of the quantitative polymerase chain reaction (qPCR) makes it a promising tool for performing large-scale screening for infectious disease among high-risk individuals. To date, no study has evaluated the specificity and sensitivity of different qPCR assays for leprosy diagnosis using a range of clinical samples that could bias molecular results such as difficult-to-diagnose cases. In this study, qPCR assays amplifying different M. leprae gene targets, sodA, 16S rRNA, RLEP and Ag 85B were compared for leprosy differential diagnosis. qPCR assays were performed on frozen skin biopsy samples from a total of 62 patients: 21 untreated multibacillary (MB), 26 untreated paucibacillary (PB) leprosy patients, as well as 10 patients suffering from other dermatological diseases and 5 healthy donors. To develop standardized protocols and to overcome the bias resulted from using chromosome count cutoffs arbitrarily defined for different assays, decision tree classifiers were used to estimate optimum cutoffs and to evaluate the assays. As a result, we found a decreasing sensitivity for Ag 85B (66.1%), 16S rRNA (62.9%), and sodA (59.7%) optimized assay classifiers, but with similar maximum specificity for leprosy diagnosis. Conversely, the RLEP assay showed to be the most sensitive (87.1%). Moreover, RLEP assay was positive for 3 samples of patients originally not diagnosed as having leprosy, but these patients developed leprosy 5-10 years after the collection of the biopsy. In addition, 4 other samples of patients clinically classified as non-leprosy presented detectable chromosome counts in their samples by the RLEP assay suggesting that those patients either had leprosy that was misdiagnosed or a subclinical state of leprosy. Overall, these results are encouraging and suggest that RLEP assay could be useful as a sensitive diagnostic test to detect M. leprae infection before major clinical manifestations.     

Cytology of testicular changes in leprosy

OBJECTIVE: To study the changes in testicular aspirates and semen of patients with leprosy. STUDY DESIGN: A prospective study of 56 patients in the reproductive-age group, with no record of treatment for leprosy. Both Ridley-Jopling and WHO classification systems were used. Skin and/or nerve biopsies were performed for documentation of the diagnosis. Semen analysis and fine needle aspirates of the testes were performed. Smears from the testicular aspirates were stained with May-Grünwald-Giemsa and Ziehl-Neelsen stain. RESULTS: Five patients were unable to produce an ejaculate. Abnormal semen analysis and/or testicular aspirates were seen in 24 (42.8%) patients. Eleven had oligospermia and eight azoospermia. Abnormalities in testicular aspirates ranged from hypospermatogenesis (4) through maturation arrest (1) and atrophy (11). Two patients had hydrocoele, and two had associated microfilariae. Three patients with multibacillary leprosy had type 2 reaction. Mycobacterium lepre was demonstrable in testicular aspirates from all patients with multibacillary and in three with paucibacillary leprosy. CONCLUSION: Abnormal semen analysis and/or testicular aspirates occur in a very high percentage of patients with leprosy. While this is expected for multibacillary disease, the high incidence in the paucibacillary form was surprising. With the rapid elimination of leprosy, fertility-related disability might emerge as a major problem in these people.     

Relapses after multibacillary leprosy treatment

Leprosy relapses are mainly due to bacillary persistence and diamino-diphenyl-sulphone (DDS) monotherapy. Case histories were examined for 33 patients with lepromatous leprosy (LL), diagnosed 7-48 years before the relapse and treated only with DDS during 4 to 38 years. Twenty-eight patients received irregular non-supervised polychemotherapy (PCT) since 1983. Five patients received only DDS, and presented relapses 13-20 years after the treatment was stopped. Relapses were diagnosed by clinical methods, including the reappearance of lesions or presence of new anesthetic areas. All cases were confirmed by bacilloscopy, and a subset of 20 cases by skin biopsy. Four patients presented indeterminate leprosy (IL) and one patient borderline tuberculoid leprosy (BT) in the biopsy. The latter 5 demonstrated presence of intraneural bacilli; the remainder were LL. Two patients relapsed even with PCT treatment. The others were cured with supervised PCT. Predisposing factors for relapses were as follows: DDS monotherapy, irregular PCT with inadequate dosage, unsupervised treatment, treatment uncompliance, and inadequate relationship between the patient and the health staff. Inspections for relapse in leprosy is recommended for in all multibacillary patients that were treated with DDS. The clinical appearance of new lesions or new anesthetic zones, the bacilloscopy and skin biopsy, used together, are effective in establishing the presence of relapses.     

Association of sinus histiocytosis with massive lymphadenopathy and idiopathic hypereosinophilic syndrome

A patient was evaluated because of edema, pruritus and generalized painless lymphadenopathy. Laboratory tests showed marked eosinophilia without known etiology. CT scan of abdomen revealed multiple lymph nodes in retroperitoneal area. Lymph node biopsy was reported as sinus histiocytosis, bone marrow biopsy showed hypercellularity with marked infiltration of normal eosinophils. During his admission he developed Coombs positive hemolytic anaemia. Once he was stable, a laparotomy was performed and the patient died two days later because of septic shock. Autopsy revealed sinus histiocytosis with massive lymphadenopathy (SHML) with extranodal involvement of duodenum, spleen and prostate; septic liver and spleen, pyelonephritis, marked infiltration of eosinophils in lymph nodes, spleen, liver duodenum and lungs. To the best of our knowledge, this is the first case report of the association of SHML and Idiopathic Hypereosinophilic Syndrome (HES).     

Paracoccidioidomycosis in a four-year-old boy

A paracoccidioidomycosis case in a four-year old boy, with fever, lymphadenopathy and hepatosplenomegaly is presented. The diagnosis was confirmed by serology and lymph node biopsy. The patient was treated with amphotericin B. After 48 hours, clinical improvement and considerable adenopathies remission were observed.     

Cytologic diagnosis of metastatic basal cell carcinoma. Report of a case with immunocytochemical and molecular pathologic considerations

BACKGROUND: Metastases of basal cell carcinoma (BCC) are extraordinarily rare events, with only about 200 published reports. The usefulness of immunohistochemical markers in the diagnosis of metastatic BCC was previously established on cytologic material. Furthermore, in recent years, numerous molecular markers have been studied to explain its pathogenesis and relatively indolent behavior. CASE REPORT: A 62-year-old, white male presented with lymphadenopathy in the right side of the neck. The patient had a long-standing history of multiple excisions of BCCs during the previous 30 years. Fine needle aspiration biopsy revealed tight clusters and sheets of small, round tumor cells with hyperchromatic nuclei, small nucleoli and minimal cytoplasm. In addition, in some of the clusters the tumor cells showed peripheral palisading. Based on the cytomorphology and diffuse immunohistochemical positivity for a low-molecular-weight cytokeratin marker, MNF 116, and negativity for AE1/AE3, Cam5.2, synaptophysin and chromogranin, a diagnosis of metastatic BCC was rendered. Subsequent histopathologic examination of metastatically involved lymph nodes removed in a radical neck dissection confirmed this diagnosis. In addition, on histologic sections the metastatic tumor cells were found to express bcl-2 and CD44, markers that have been recently studied in cutaneous tumors. CONCLUSION: In acquiring metastatic potential, this lesion did not lose the molecular characteristics of bcl-2 and CD44 expression, the two features deemed to be important in the indolent behavior of BCC.     

Morphologic aspects in primary cryptococcosis of the skin

Two cases of cryptococcus infection of the skin were presented. Both — of the mammary and of the lower lip region — were admitted as probable cancers. The right diagnosis has been proved by biopsy, Alcian-Blue stain and fungus culture. The morphologic investigation showed the following characteristic features: a granuloma with dispersed proliferation of foam, epithelioid and giant cells, and with suppuration. In the cells ‘empty holes’ with sharp borders and some minute unstained particles are present, that in Alcian-Blue stain give a positive reaction.     

Cytodiagnosis of erythema nodosum leprosum. A case report

BACKGROUND: The application of cytology in leprosy has been restricted to the evaluation of morphologic and bacterial indices by slit skin smears to facilitate diagnosis of cases according to the Ridley-Jopling scale. Isolated reports have now documented the use of fine needle aspiration cytology (FNAC) in the diagnosis of leprosy. CASE: A 45-year-old male presented with the abrupt onset of multiple nodular eruptions all over the body. The clinical diagnosis was Sweet's syndrome. FNAC showed numerous neutrophils in a background of foamy macrophages. Special stains revealed the presence of a large number of fragmented acid-fast bacilli in the smears. A diagnosis of erythema nodosum leprosum (ENL) was made on FNAC. CONCLUSION: The presence of neutrophils in a characteristic milieu of foamy macrophages is seen in lesions of ENL. Such a picture should prompt the cytologist to use a modified Ziehl-Neelsen stain to demonstrate acid-fast bacilli, as ENL can present as an acute episode in patients without a previous diagnosis of leprosy.     

Extrapulmonary Pneumocystis carinii infection in an AIDS patient: a case report

BACKGROUND: Extrapulmonary Pneumocystis carinii (EPC) infection is an uncommon condition, regardless of HIV status, and can occur as a complication of P carinii pneumonia (PCP). However, PCP is the most common severe opportunistic infection in patients with AIDS. The incidence of EPC is variable, and in HIV-1-infected individuals it has been estimated to be 0.06-2.5%. CASE: A case of generalized lymphadenopathy was referred to us for fine needle aspiration cytology (FNAC). The patient was a 9-year-old boy who had a toxic facies and manifested multiple skin lesions all over the body. Fever was present during the examination. HIV status was confirmed from the history and test report. FNAC was done from a cervical lymph node and smears stained with hematoxylin-eosin and with Giemsa and Papanicolaou stain. The presence of P carinii was suspected in Giemsa- and hematoxylin-eosin-stained smears, and silver methenamine stain was used to confirm the diagnosis. Fungal spores were seen as small, spherical cysts of variable sizes, more or less the size of erythrocytes. The diagnosis was thus established as EPC infection. CONCLUSION: Lymph node involvement is the most common site of pneumocystosis in AIDS patients. Fine needle aspiration diagnosis of EPC infection is a possibility in such cases with lymphadenopathy and must be included in the differential diagnosis of lymph node swellings in AIDS.