Well-formed Granulomas Research Articles

Characterization of theHistoplasma capsulatum-Induced Granuloma

Rising rates of Histoplasma capsulatum infection are an emerging problem among the rapidly growing population of immune-compromised individuals. Although there is a growing understanding of systemic immunity against Histoplasma, little is known about the local granulomatous response, which is an important component in the control of infection. The focus of this article is the characterization of Histoplasma-induced granulomas. Five days after i.p. infection, infected macrophage appear in the liver and lung; however, no granulomas are apparent. Two days later, well-formed sarcoid granulomas are abundant in the lung and liver of infected mice, which contain all visible Histoplasma. Granulomas are dominated by macrophage and lymphocytes. Most of the Histoplasma and most of the apoptotic cells are found in the center of the lesions. We isolated liver granulomas at multiple time points after infection and analyzed the cellular composition, TCR gene usage, and cytokine production of granuloma-infiltrating cells. The lesions contain both CD4+ and CD8+ T cell subsets, and T cells are the primary source of IFN-gamma and IL-17. The main source of local TNF-alpha is macrophage. Chemokines are produced by both infiltrating macrophage and lymphocytes. Dendritic cells are present in granulomas; however, T cell expansion seems to occur systemically because TCR usage is very heterogeneous even at the level of individual lesions. This study is the first direct examination of host cellular responses in the Histoplasma-induced granuloma representing the specific interface between host and pathogen. Our studies will allow further analysis of key elements of host Histoplasma interactions at the site of chronic infection.

A Woman with Cough, Fever, and Micronodular Infiltrates on Chest Radiograph

Hot tub lung is a form of hypersensitivity pneumonitis (HP) reported to be associated with exposure to large aerosolized inocula of Mycobacterium avium complex (MAC). Although the pathogenesis of the disease is still poorly understood, the pathology of MAC-related HP can be similar to that of sarcoidosis, with well-formed granulomas. We describe a patient with HP featuring well-formed granulomas on transbronchial biopsy specimens, a finding believed to be unique to MAC-related HP, also referred to as "hot tub lung".

A case of Crohn’s disease involving the gallbladder

Crohn's disease is well known to affect any part of the gastrointestinal tract including the oral cavity and anus. Various extraintestinal complications have been reported in Crohn's disease, but extraintestinal involvement characterized by granulomatous lesions is uncommon. Here, we have reported a case about the involvement of the gallbladder in Crohn's disease. A 33-year-old woman was diagnosed having panperitonitis due to intestinal perforation and cholecystitis. The patient was moved to the surgical service for an emergency operation. On the resected specimen, there was a broad longitudinal ulcer at the mesenteric side. The mucosa of the gallbladder was nodular and granular, and the wall was thickened. The surface epithelium of the gallbladder was partially eroded and pyloric gland metaplasia was observed focally. Rokitansky-Aschoff sinuses were also present. From the lamina propria to the subserosal layer, there were several well-formed epithelioid cell granulomas, which were the non-caseating sarcoidal type different from the foreign-body and xanthomatous granulomas. Periodic-acid Schiff and acid fast stains revealed no organism within the granulomas. Lymphoid aggregates were present throughout the gallbladder wall. Sections from the resected ileum showed typical features of the Crohn's disease. When cholecystectomy is performed in a patient with Crohn's disease, the possibility of gallbladder involvement should be carefully examined by histopathological tests.

Clinical, Colonoscopic, and Histological Profile of Colonic Tuberculosis in a Tertiary Hospital

Colonic tuberculosis is not uncommon in developing countries. As emigration to the West increases, it is worthwhile to recall the clinical, colonoscopic, and histopathological features of this condition. The clinical, colonoscopic and histopathological findings were evaluated in 43 patients with colonic tuberculosis. Abdominal pain, weight loss, diarrhea, fever, and a lump in the abdomen were the commonest symptoms. Extraintestinal tuberculosis was present in 11 patients (26 %). Colonoscopy revealed ulcers in 30 patients (70 %), nodules in 24 (56 %), a deformed cecum and ileocecal valve in 17 (40 %), strictures in 10 (23 %), polypoid lesions in six (14 %), and fibrous bands forming mucosal bridges in three (7 %). The cecum and ascending colon were the commonest sites involved. Segmental tuberculosis was seen in six of the 32 patients (19 %) in whom full-length colonoscopy could be performed. Two or more sites were involved in 19 patients (44 %). Histopathology revealed well-formed granulomas in 23 patients (54 %). Fourteen of the above patients (61 %) had caseation and 11 (48 %) had confluence of the granulomas. Acid-fast bacilli were present in the biopsies from two patients (5 %). Ill-formed granulomas were seen in seven patients (16 %) and chronic inflammatory changes in 13 (30 %). Despite the various histopathological findings, all of the patients responded to antitubercular treatment and continued to remain asymptomatic during the follow-up period. Colonoscopy with biopsy is a useful method for diagnosing colonic tuberculosis. Even in the absence of the classic histopathological features, a therapeutic trial may be indicated in a given clinical and colonoscopic setting. Follow-up is essential.

Doseamento das granzimas A e B na sarcoidose pulmonar (estudo experimental)

Sarcoidosis is a systemic disease of unknown aetiology, morphologically characterized by well-formed epithelioid granulomas, which show little or no cen-tral necrosis. These may be present in any organ or tissue. The lung is the most frequently and promi-nently involved target.The granuloma is often very sharply demarcated from the adjacent tissue and is surrounded by a mantle of lymphocytes, which mediate lysis of target cells by various mechanisms, including exocytosis of lytic proteins, perforins and granzymes.Sarcoidosis laboratorial diagnosis is usually made by SACE and Lisozyme dosages. The granzymes A and B could be two other markers of the disease, since the sarcoidosis granuloma is rich in cytotoxic and NK cells.An ELISA Kit was used to measure Granzyme A and B in serum of a normal control group (NC) (n=30), and in two groups with lung pathology: one without sarcoidosis, disease control (DC) (n=21) and other with sarcoidosis (S) (n=11).Our results showed that SACE activity is significantly augmented in S group comparing with NC and DC, respectively: 82,6±32,7/31,9±17,8 - p=0,00017 and 82,6±32,7/31,9±17,8 - p=0,00024. Lisozyme activity is significantly augmented in S and DC groups comparing with NC. Granzyme B showed a significant decrease in DC and S groups comparing with NC. Granzyme A showed a significant decrease between S/NC groups.Our results suggest that the decrease of Granzyme A and B in sarcoidotic patients could be related to an ineffective inflammatory local response related to the formation of sarcoidosis granulomas. More studies are needed, particularly in BAL.Rev Port Pneumol 2005; XI (2): 111-133

Hypersensitivity Pneumonitis Reaction to Mycobacterium avium in Household Water

Hypersensitivity pneumonitis has been described with exposure to aerosolized Mycobacterium avium complex (MAC) in indoor hot tubs (hot tub lung). To describe a case of MAC-associated hypersensitivity pneumonitis-like reaction possibly from showering and review previous hot tub lung reports. For the case report, we investigated a patient with histologically diagnosed hypersensitivity pneumonitis and MAC-positive sputum culture findings. Mycobacterial cultures were obtained from his home and workplace. Isolates were typed using pulsed-field gel electrophoresis. For the review, MEDLINE and EMBASE were searched for hot tub lung reports, which were reviewed and summarized. A 50-year-old man had progressive dyspnea and episodic fever and myalgias. Pulmonary function testing results revealed obstruction and impaired diffusion; a chest CT scan found diffuse, centrilobular, ground-glass nodules, and air trapping, and a lymphocytic alveolitis with an elevated CD4/CD8 ratio. Transbronchial biopsy showed multiple well-formed nonnecrotizing granulomas. Multiple respiratory samples and shower and bathtub specimens grew MAC, with matching pulsed-field gel electrophoresis patterns. The patient changed from showering to tub bathing. Prednisone and antimycobacterial drugs were administered for approximately 1 year. His symptoms, pulmonary function abnormalities, and CT scan findings resolved. The literature review yielded 36 cases of hot tub lung. Clinical features included dyspnea (97%), cough (78%), and fever (58%). Pulmonary function testing showed obstruction (67%), restriction (55%), and impaired diffusion (75%). A chest CT scan showed ground-glass opacification (95%) and nodules (67%). Granulomas were well-formed in 95%. Treatments included discontinuation of hot tub use and prednisone, antimycobacterial drugs, or both. Outcomes were favorable. A hypersensitivity pneumonitis-like reaction to mycobacteria can occur from exposures other than hot tubs. There are key differences between classic hypersensitivity pneumonitis and MAC-associated hypersensitivity pneumonitis. Antimycobacterial therapy may be required. The possibility of MAC hypersensitivity pneumonitis from showering raises potential implications in the investigation of patients with hypersensitivity pneumonitis.

Bone marrow pathology in AIDS

Bone marrow morphology is frequently abnormal in patients with AIDS. In this study, we reviewed 97 bone marrow biopsies of AIDS patients performed between 1998 and 2000 in the Emı́lio Ribas Institute of Infectology, which is the reference department for HIV. Specific diagnoses were performed in 33 cases. Fungi were observed in eight cases. Five of them were Histoplasma capsulatum, two were Cryptococcus neoformans, and one probably Candida albicans. Acid-fast bacilli were observed in 12 bone marrow biopsies, three of which were diagnosed to have no mycobacteriosis clinically. Foci of necrosis with clusters of macrophages without any well-formed granuloma were observed in nine cases and well-formed granuloma in three cases. Lymphomatous infiltration was observed in four cases of non-Hodgkin's lymphoma and in two Hodgkin's diseases (mixed cellularity). Extensive necrosis of bone marrow was observed in one case of Burkitt's lymphoma. In conclusion, bone marrow biopsy should be performed to elucidate the etiology of cytopenias, secondary infections, and fever of undetermined origin in AIDS patients.

Granuloma annulare with a mycosis fungoides–like distribution and palisaded granulomas of CD68-positive histiocytes

We describe 3 unusual cases of granuloma annulare with multiple macular lesions in a distribution that simulated mycosis fungoides in patients with no associated underlying diseases. Repeated biopsies showed typical well-formed palisading granulomas and no evidence of an atypical lymphocytic infiltrate. There was no vasculitis, neutrophilic, eosinophilic, or interstitial infiltrate. The patients had no associated underlying diseases. Most of the histiocytes in the palisading granulomas were strongly positive for CD68. The lymphocytes were a minor component of the granulomatous inflammation and were predominantly CD8 + T-cells. The findings in these cases add to the spectrum of previously defined granulomatous eruptions of the skin.

Interstitial heparan sulfate in granulomatous inflammatory skin diseases

Background Heparan sulfate (HS) is a glycosaminoglycan that is anchored to the outside of cell membranes. Under ordinary circumstances, it is not present in the interstitium, but under certain circumstances, mainly in the setting of inflammation and tissue repair, HS can be shed from the cell surface into the interstitium in a regulated fashion. Under these circumstances, interstitial HS seems to have an immunomodulatory function because of its binding of many cytokines. However, it is not known which cell types present at an inflammatory site are responsible for this shedding. Objective We have investigated the presence of interstitial HS by immunohistochemistry in various inflammatory skin diseases characterized by different compositions of the inflammatory infiltrate. Results Strong interstitial HS immunoreactivity was present only in diseases with a predominantly histiocytic infiltrate but not in diseases with a predominantly lymphocytic or neutrophilic infiltrate. Conclusions This indicates that histiocytes have a direct or indirect role in the HS shedding process. In the well-formed granulomas of sarcoidosis, interstitial HS immunoreactivity was spatially associated with the fibrotic ring at the periphery of the granulomas, but not with the center harboring the histiocytes. This suggests that histiocytes can stimulate fibroblasts to shed HS into the interstitium.

Morphometric analysis of Th 1 and Th 2 cytokine expression in human pulmonary tuberculosis

Following infection with Mycobacterium tuberculosis, host cytokine responses influence disease manifestation. Differences in cytokine expression likely determine whether tuberculosis (TB) progresses, resolves, or becomes latent. In particular, the balance between Th(1) and Th(2) cytokine responses influences the expression of disease in individuals with pulmonary TB. Since the cytokine microenvironment in pulmonary TB remains suboptimally defined, we utilized quantitative immunohistochemistry to compare the expression of Th(1) cytokines [interferon-gamma (IFNgamma) and interleukin-12 (IL-12)] and Th(2) cytokines [IL-4, IL-10, transforming growth factor-beta (TGFbeta)] in surgically resected lungs of seven TB patients and four control subjects. We also quantified IFNgamma-inducible protein 10 (IP-10) expression, a CXC chemokine for macrophages and T cells. Morphometric analyses revealed increased IFNgamma, IL-12, IP-10, and TGFbeta in granulomas and in pneumonitis areas of TB lungs. In contrast, IL-10 and IL-4 expressions were globally reduced in TB lung tissues compared to controls. Th(1) cytokines and TGFbeta are increased while Th(2) cytokines are decreased in well-formed pulmonary granulomas of TB patients compared to controls.

Comparison of polymerase chain reaction with histopathologic features for diagnosis of tuberculosis in formalin-fixed, paraffin-embedded histologic specimens.

Objective.-To investigate the relationship between various histopathologic features and the results of the tuberculosis (TB)-polymerase chain reaction (PCR) method in routinely submitted histologic specimens for the histopathologic diagnosis of TB. Design.-We used 95 formalin-fixed, paraffin-embedded tissue blocks from 81 patients who were clinically suspected of having TB. We assessed the presence of histopathologic features including well-formed granuloma, poorly formed granuloma, caseous necrosis, and Langhans-type giant cells. We performed nested PCR for IS6110 and Ziehl-Neelsen staining for acid-fast bacilli (AFB). Results.-Of the 81 patients studied, 53 patients had chronic granulomatous inflammation, whereas 28 patients had only chronic inflammation without definite granulomatous inflammation. Of the 53 cases with chronic granulomatous inflammation, 17 (32%) were AFB positive and 36 (68%) were TB-PCR positive. Among cases with chronic granulomatous inflammation, the percentage that were positive and negative by TB-PCR differed significantly with the presence of various histopathologic features. All of the 13 cases with well-formed granuloma, caseous necrosis, and Langhans-type giant cells were TB-PCR positive; however, 10 (36%) of the 28 cases with chronic inflammation without granulomatous lesions were also TB-PCR positive. Conclusions.-TB-PCR is a rapid, sensitive method for the diagnosis of TB in routinely processed formalin-fixed, paraffin-embedded histologic specimens and is readily available in histopathology laboratories. We recommend use of TB-PCR when TB is suspected clinically, especially in cases of chronic inflammation without definite evidence of granulomatous inflammation.

Polymerase Chain Reaction for Diagnosis of Cutaneous Leishmaniasis in Histologically Positive, Suspicious and Negative Skin Biopsies

Background: Cutaneous leishmaniasis (CL) is a major problem in many tropical and subtropical countries. The clinical diagnosis should be confirmed by identification of the parasite in biopsy or smear or by tissue culture. The sensitivity of direct microscopy is not high, and tissue culture is not uniformly available and successful. Polymerase chain reaction (PCR) is a sensitive test for the detection of low amounts of DNA in tissues. Objective: We applied PCR on paraffin-embedded skin biopsies to assess the validity of this method in the diagnosis of cutaneous leishmaniasis. Methods: DNA extraction from paraffin blocks was performed by the heat method, and PCR was carried out using the primers for the Leishmania-specific 120-base-pair fragment of kinetoplast DNA minicircles. Paraffin blocks of gelatin-embedded formalin-fixed Leishmania tropica, taken from culture, served as positive controls. Negative controls were the skin biopsies of patients whose clinicopathologic diagnoses were not cutaneous leishmaniasis. Results: PCR showed the parasite in all 33 cases whose skin biopsies had shown the Leishmania parasite by light microscopy. PCR results were also positive in 24 cases out of 29 where microscopic examination of skin biopsies had failed to detect the amastigote but their clinical diagnosis was CL. The sensitivity of PCR in the diagnosis of CL was 92%. None of the nonleishmaniasis cases showed positive results (specificity 100%). PCR results were positive in 52 out of 54 cases whose skin biopsies showed granulomatous inflammation. Evaluation of the histopathologic findings showed that the presence of vaguely formed immature granuloma was directly and the detection of mature well-formed granuloma was inversely correlated with the detection of the parasite in biopsies (p < 0.01). Conclusion: PCR on paraffin-embedded tissue is a highly sensitive and specific test for the diagnosis of CL, and detection of granulomatus inflammation is a highly reliable histopathologic finding in suspected cases.

Increased expression of fas ligand in human tuberculosis and leprosy lesions: a potential novel mechanism of immune evasion in mycobacterial infection.

To study the location and mechanism of apoptosis within the human tuberculosis (TB) and leprosy lesions, parallel sections were analyzed for mycobacterial antigens (M.Ag), Fas ligand (FasL), Fas, CD68 and Mac387 by immunohistochemistry, and apoptotic cells by the terminal deoxynucleotidyl-transferase-mediated dUTP-digoxigenin nick end labelling method. Cutaneous leishmaniasis and foreign body granulomas were analyzed for comparison. The heavily infected macrophages in multibacillary TB and leprosy granulomas very strongly expressed FasL, indicating that a mycobacterial infection can induce an increased expression of FasL in a population of infected macrophages, which may protect them from the attack of Fas-expressing lymphocytes. However, macrophages with high levels of leishmania amastigotes did not selectively express FasL, suggesting that this phenomenon is specific for the mycobacteria. Interestingly, in the well-formed TB granulomas, 84% of the multinucleated giant cells strongly expressed FasL. The expression of Fas was weak (34%) or absent. A higher number (33%) of epithelioid cells expressed FasL than Fas (23%). Lymphocytes were scanty among the epithelioid cells. The frequency of apoptotic cells was higher in the epithelioid cells (0.25%) than the mononuclear cells in the mantle zone (0.14%). Thus, the epithelioid cells and the multinucleated giant cells by virtue of the increased expression of FasL may make these granulomas an immune privileged site for mycobacteria.

Pulmonary Nocardiosis in a Patient With Human Immunodeficiency Virus

A man was admitted to the hospital with a 3-week history of dry cough, anorexia, weakness, and weight loss. The patient was positive for human immunodeficiency virus and was noncompliant with prescribed antiretroviral medications. His CD4 count and viral load were unknown at the time of admission. A chest radiograph revealed diffuse cystic and bullous changes and coarse reticular markings throughout both lung fields, consistent with chronic, most likely postinfectious, fibrotic changes, possibly with a superimposed active infectious process (Figure 1). The patient underwent bronchoscopy and bronchoalveolar lavage. Transbronchial biopsies of the right lower lobe were obtained. Material was submitted for bacterial, fungal, and viral cultures, and for histopathologic examination. Acid-fast bacilli were seen on the smear from bronchial secretions by the auramine-rhodamine method. A presumptive diagnosis of mycobacterial infection was made. Mycobacterium xenopi was subsequently isolated from mycobacterial culture. Routine bacterial, fungal, and viral cultures were negative. Microscopic examination of transbronchial biopsies demonstrated extensive inflammatory infiltrate involving bronchial tissue and expanding adjacent alveolar interstitium. The infiltrate consisted of plasma cells, lymphocytes, histiocytes, neutrophils, and rare multinucleated giant cells (Figure 2, original magnification 3400). Well-formed granulomas were not seen. Ziehl-Neelsen stains for acid-fast bacilli were negative. Gomori methenamine silver stain, Gram stain, and modified acid-fast Fite stain (Figure 3, oil immersion, original magnification 31000) revealed the presence of gram-positive, branching, filamentous, beaded bacteria morphologically diagnostic of Nocardia species. Nocardia species belong to the group of aerobic bacteria generically designated as actinomycetes. They are ubiquitous environmental saprophytes living in soil, organic matter, and water.1 Nocardiae have long been known to cause disease in animals and are being recognized increasingly as opportunistic human pathogens. The organism does not elicit a humoral response and is eliminated from the body via cell-mediated mechanisms. Thus, individuals with impaired T-cell function are at increased risk for nocardial infection. Groups at the highest risk in-

Pulmonary Nocardiosis in a Patient With Human Immunodeficiency Virus

A man was admitted to the hospital with a 3-week history of dry cough, anorexia, weakness, and weight loss. The patient was positive for human immunodeficiency virus and was noncompliant with prescribed antiretroviral medications. His CD4 count and viral load were unknown at the time of admission. A chest radiograph revealed diffuse cystic and bullous changes and coarse reticular markings throughout both lung fields, consistent with chronic, most likely postinfectious, fibrotic changes, possibly with a superimposed active infectious process (Figure 1). The patient underwent bronchoscopy and bronchoalveolar lavage. Transbronchial biopsies of the right lower lobe were obtained. Material was submitted for bacterial, fungal, and viral cultures, and for histopathologic examination. Acid-fast bacilli were seen on the smear from bronchial secretions by the auramine-rhodamine method. A presumptive diagnosis of mycobacterial infection was made. Mycobacterium xenopi was subsequently isolated from mycobacterial culture. Routine bacterial, fungal, and viral cultures were negative. Microscopic examination of transbronchial biopsies demonstrated extensive inflammatory infiltrate involving bronchial tissue and expanding adjacent alveolar interstitium. The infiltrate consisted of plasma cells, lymphocytes, histiocytes, neutrophils, and rare multinucleated giant cells (Figure 2, original magnification 3400). Well-formed granulomas were not seen. Ziehl-Neelsen stains for acid-fast bacilli were negative. Gomori methenamine silver stain, Gram stain, and modified acid-fast Fite stain (Figure 3, oil immersion, original magnification 31000) revealed the presence of gram-positive, branching, filamentous, beaded bacteria morphologically diagnostic of Nocardia species. Nocardia species belong to the group of aerobic bacteria generically designated as actinomycetes. They are ubiquitous environmental saprophytes living in soil, organic matter, and water.1 Nocardiae have long been known to cause disease in animals and are being recognized increasingly as opportunistic human pathogens. The organism does not elicit a humoral response and is eliminated from the body via cell-mediated mechanisms. Thus, individuals with impaired T-cell function are at increased risk for nocardial infection. Groups at the highest risk in-

Sinocranial aspergillosis: a form of central nervous system aspergillosis in south India.

Of the 21 patients with aspergillosis of central nervous system seen during the years 1990-1997, 16 (76%) had aspergillosis of sino-cranial origin. The occupation in patients with sino-cranial aspergillosis was either agricultural or manual work and predisposing risk factors were present in only two (12.5%) patients. Skull-base syndromes were the presenting features in 13 patients and three patients presented with features of intracranial space-occupying lesion. Paranasal sinus mass lesions were seen in all the 16 patients. Computerized tomography showed intracranial extradural-enhancing mass lesions in the anterior, middle or posterior cranial fossa in nine (68%) patients, intracranial and orbital lesions in four and orbital lesions in three. Well-formed granuloma with dense fibrosis was the histological feature. Survival rates were not good even after surgical and antifungal chemotherapy. Surgical treatment was subradical in our series. The majority of cases of sinocranial aspergillosis are reported from countries with temperate climates and the high incidence in these regions is probably related to constant exposure to the high spore content of pathogenic Aspergillus species in the 'mouldy' work environment.

The pathologic spectrum of gastrointestinal and hepatic histoplasmosis.

We characterized the pathologic spectrum of lesions in gastrointestinal and hepatic histoplasmosis by studying cases of disseminated disease in immunocompromised and immunocompetent patients from endemic and nonendemic areas. We evaluated 56 specimens from 52 patients with H&E and silver stains. Of these patients, 43% presented with gastrointestinal rather than pulmonary symptoms. Thirty-one percent had gastrointestinal lesions, 10% had liver lesions, and 43% had both. Gross gastrointestinal features included ulcers (49% of patients), nodules (21%), hemorrhage (13%), obstructive masses (6%) and normal mucosa (23%). Microscopic gastrointestinal findings included diffuse lymphohistiocytic infiltration (83%), ulceration (45%), lymphohistiocytic nodules (25%), or minimal inflammatory reaction (15%) but only rare well-formed granulomas (8.5%). The most common hepatic finding was portal lymphohistiocytic inflammation; discrete hepatic granulomas were seen in less than 20% of involved livers. The pathologist must be aware of the broad range of gastrointestinal and hepatic lesions produced by histoplasmosis and, in particular, that well-formed granulomas are rare. Given the appropriate clinical context, histoplasmosis should be considered in both immunocompetent and immunocompromised patients, regardless of pulmonary symptoms, in nonendemic as well as endemic areas.

Histologic reactions to cutaneous infections by Mycobacterium haemophilum.

Mycobacterium haemophilum is an emerging pathogen in immunocompromised patients. We report the clinical and histologic findings of 16 skin biopsies from 11 patients with culture-proven infections by M. haemophilum. The patients had leukemia or non-Hodgkin's lymphoma. Ten of them had undergone bone marrow transplantation. When the skin biopsy specimens were taken, a portion of the skin was simultaneously submitted to a microbiology laboratory for cultures. The remaining skin was processed routinely. Acid-fast bacilli were found in 11 of 16 lesions. The number of histologically detectable organisms was typically low: nine biopsies had fewer than three bacilli per 50 oil immersion fields. The most common histologic pattern was a mixed suppurative and granulomatous reaction (7 of 16 biopsies). Four biopsies showed well-formed epithelioid granulomas. Two showed necrosis, one of which was ulcerated. One lesion was a subcutaneous abscess. Two biopsies showed a mixed lichenoid and granulomatous dermatitis. In one of them, the granulomatous reaction was focal and small. One biopsy lacked a granulomatous tissue reaction altogether; it showed an interface dermatitis, a perivascular and periadnexal lymphocytic infiltrate, and necrotizing lymphocytic small vessel vasculitis. A subsequent biopsy from the same patient additionally showed a focal granulomatous reaction. Our observation that infections by M. haemophilum can present with nongranulomatous or pauci-granulomatous reactions without necrosis is of note. Failure to suspect mycobacterial infection in such reactions contributes to probable underreporting of M. haemophilum and to misdiagnoses. Furthermore, our findings emphasize the importance of simultaneous biopsies for culture and histology in immunocompromised patients.

Granulomatous Lobular Mastitis Following Drug-Induced Galactorrhea and Blunt Trauma.

We report a single case of chronic granulomatous lobular mastitis following metoclopramide-related galactorrhea and a blunt trauma in a young parous woman who underwent two conservative operations before becoming symptom-free. We have found only two other literature cases associated with hyperprolactinemia, and our case could be another of this etiologic group. The absence of well-formed granulomas in the first histology specimen in the present case was misleading; it was reinterpreted as granulomatous mastitis only after the second specimen was examined. Reinterpretation was based on the lobular distribution of a lymphoplasmocytic infiltrate (nonspecific chronic lobulitis) and the presence of epithelioid cell sheets and neutrophils in the absence of well-formed granulomas. The case lends further support to the theory of a local immune response initiated by the secreted material or by one of its components in the formation of granulomas. However, contributory factors such as the trauma in this case (a blow from a shovel handle) or systemic disease in others may play a role in the development of the disease, which in some instances may represent a pattern of tissue reactions to different noxious agents.

Utility of fine-needle aspiration in the diagnosis of panniculitis.

This is a retrospective reassessment of the most important cytopathologic features of 23 FNA smears with a cytologic diagnosis of panniculitis (PN). Patients were sent by clinicians. Clinical diagnoses were as follows: 16 suspicious of PN; three cutaneous metastases of an extracutaneous primary neoplasm; four with no clinical diagnosis. Thirteen cases were subsequently submitted to histopathologic study. The following cytoarchitectural patterns were found to be very useful for the cytologic diagnosis of PN: adipocytes intermingled with foamy histiocytes, donut-like granulomas, aggregates of adipocytes intermingled with plump histiocytes, a granular basophilic background forming a lattice-like pattern, and well-formed granulomas with or without multinucleated giant cells. Inflammatory cells could be seen combined with any of these cytoarchitectural patterns. FNA does not pretend to replace excisional biopsy as the diagnostic procedure for these entities but it is a very useful diagnostic tool in certain cases: for confirming the recurrence of PN previously diagnosed by histology, for evaluating the onset of subcutaneous nodules in patients with a non-cutaneous malignant primary neoplasm, for evaluating cutaneous nodules with no clinical suspicion, and for confirming a clinical diagnosis of PN and differentiating it from other entities that mimic PN clinically.