Granulomatous Inflammatory Infiltrate Research Articles

S2772 Subcutaneous Sweet Syndrome Successfully Treated With Ustekinumab in Patient With Ulcerative Colitis

Introduction: Extraintestinal manifestations (EIMs) of inflammatory bowel disease (IBD) are well-established. Sweet syndrome (SS), or acute febrile neutrophilic dermatosis, is a reactive mucocutaneous manifestation of IBD presenting as erythematous papules/plauqes with associated fever and arthomyalgias. There is limited evidence regarding efficacy of Ustekinumab in management of EIMs of UC, particularly SS. Case Description/Methods: The patient is a 50-year-old woman with left-sided UC (Montreal classification E2) that previously failed several therapies, including mesalamine, azathioprine, infliximab, adalimumab, vedolizumab, and a fecal microbiota transplant trial. She presented with worsening abdominal pain, diarrhea/hematochezia, and bilateral lower extremity pain. She was febrile and tachycardic with tender, violaceous, and ulcerated subcutaneous nodules on the bilateral ankles with hemorrhagic bullae (FigureA). Labs revealed negative C. diff, elevated ESR/CRP, thrombocytosis, and borderline leukocytosis with neutrophilic predominance. Lower extremity MR imaging and bone biopsy revealed multifocal sterile osteomyelitis with adjacent abscess; skin biopsy demonstrated dense granulomatous/neutrophilic infiltrate in the deep dermis/subcutis without microorganisms, consistent with subcutaneous SS (FigureB). A restaging colonoscopy demonstrated severe proctosigmoid ulcerative colitis (FigureC). Given that the patient had failed several immunomodulators and biologic therapies, she was started on prednisone and Ustekinumab. Four months later, she reported complete resolution of her cutaneous SS off steroids and improving UC symptoms (less frequent and more formed stools, minimal hematochezia). Repeat MRI demonstrated resolution of the sterile osteomyelitis and abscess. Discussion: Our case highlights the novel use of Ustekinumab in the treatment of subcutaneous SS with sterile osteomyelitis in a patient with flaring UC. SS is a neutrophilic dermatosis that is a rare EIM of IBD, classically characterized by tender cutaneous lesions. There is limited evidence supporting the use of Ustekinumab in treating EIMs of CD, and a lack of data regarding its efficacy in treating EIMs of UC. Our case fills a major gap in the literature and highlights the clinical efficacy of Ustekinumab for SS and UC especially in patients that have a contraindication to, failed previous treatment with, or otherwise cannot tolerate corticosteroids and TNF-alpha antagonists.Figure 1.: 1A. Right lateral malleolus with 2.5 cm shallow erosion with slightly violaceous borders and central bright yellow fibrinous debris. There was slight atrophy of surrounding skin with mild edema and hyperpigmentation (left image). Left medial malleolus/dorsal foot with grouped irregular shallow ulcers with surrounding mild violaceous erythema (middle and right image). 1B. Left ankle biopsies showed mixed septal and lobular panniculitis with granulomatous and neutrophilic inflammation. Histologic sections show a mildly spongiotic epidermis with dense granulomatous and neutrophilic inflammatory infiltrate in the deep dermis and subcutis (left image). The inflammatory infiltrate, which consists of prominent neutrophils, histiocytes, and scattered lymphocytes, surrounds vascular and adnexal structures, as well as adipocyte lobules. Definitive features of vasculitis are not seen. PASd (periodic acid-Schiff-diastase), GMS (Grocott’s methenamine silver), Gram, and Fite staining fail to highlight microorganisms (right image). 1C. Colonoscopy demonstrated severe (Mayo Endoscopy Score 3) proctosigmoid ulcerative colitis to 30 cm (left image). Sigmoid biopsies showed significant immune cell infiltration with crypt architectural distortion concerning for severe chronic active colitis. No evidence of granulomas, dysplasia or cytomegalovirus (right image).

An underrated differential diagnosis for subcutaneous lumps: 26 cases of subcutaneous Dirofilariasis

IntroductionEven though subcutaneous dirofilariasis [worm granuloma] is an emerging zoonosis, it is not commonplace to consider it as a differential diagnosis for a subcutaneous lump even in the endemic zones. Moreover, the available literature lacks attempts to provide a unified clinical profile for it to be considered as a clinical entity.Methods We have retrospectively analyzed patients who were diagnosed with subcutaneous dirofilariasis at a Base Hospital in the Uva Province of Sri Lanka from February 2018 to March 2020. We evaluated patient demographics, symptomatology, clinical signs, ultrasonographic and histopathological features.Results Twenty-six patients with a mean age of 15.6 years [range 1 – 67 years] were analyzed. The locations of the lumps were highly variable, the commonest being the abdominal wall [34.6%]. Most [84.6%] were asymptomatic. The average diameter was 14.2mm [range 8 – 25mm]. The majority were neither tender nor warm, firm, and had ill-defined margins and a smooth surface without fluctuation, transillumination, or slipping sign. All were in the subcutaneous plane often attached to the deep fascia but without attachment to the skin. Blood investigations were unremarkable with a normal ESR and eosinophil count. The ultrasonographic finding was an echogenic tubular structure within a hypoechoic lesion. Histopathology demonstrated a worm surrounded by granulomatous inflammatory infiltrates with eosinophils and lymphocytes. Conclusion We emphasize the importance of regarding subcutaneous dirofilariasis as a differential diagnosis for subcutaneous lumps, especially in the highly prevalent geographical zones to minimize 'incidental diagnosis'.

Clinical Profile of Melkersson-Rosenthal Syndrome/Orofacial Granulomatosis: A Review of 51 Patients.

Melkersson-Rosenthal syndrome (MRS) is a rare disease characterized by the triad of granulomatous cheilitis, fissured tongue, and facial paralysis. Publications concerning large series are rare in the literature. To describe the clinical and histopathological characteristics of patients with complete and oligosymptomatic forms of MRS. A retrospective records review was performed for the diagnoses of Melkersson-Rosenthal syndrome, granulomatous cheilitis, and orofacial granulomatosis at oral Diseases Clinic of the Department of Dermatology, University of São Paulo, Brazil (2003, 2017). A total of 51 patients were included, mean age at presentation 35.69 years. Four patients were younger than 18 years. The complete triad of was observed in 10 patients. The rare findings of granulomatous blepharitis, gingivitis and palatitis are presented. Comorbidities included Crohn's disease (5 patients), migraine headaches (1 patient) and convulsions (2 patients). Granulomatous inflammatory infiltrate was detected in 31 biopsies. Medical therapies included included oral and intralesional steroids, thalidomide, dapsone, azathioprine, tetracycline, methotrexate, and surgery, with variable responses. Our report meant to draw attention to the clinical spectrum of this rare disorder, mainly to oligosymptomatic forms and rarer presentations.

Persistence pays: a case of primary cutaneous B-cell lymphoma masked by granulomas

<p class="abstract">Primary cutaneous diffuse large B cell lymphoma is a form of cutaneous lymphoma characterized by a clonal proliferation of B cells that is often presents with a delayed diagnosis, and therefore often carries poor prognosis. We report a 77-year-old female presenting with a shin lesion resembling a deep dermal or fungal process. Initial biopsy revealed superficial and deep mixed granulomatous inflammatory infiltrate, which suggested an initial diagnosis of Majocchi’s granuloma, despite negative fungal cultures. Despite treatment, the progressive worsening of the skin lesions prompted multiple repeat biopsies, which eventually revealed CD20, Bcl-2, and Bcl-6 staining, loss of CD3 and CD30, and high Ki67, compatible with a cutaneous high-grade B-cell lymphoma. Clinical presentations of primary cutaneous diffuse large B cell lymphoma can mimic several different clinical entities, rarely including granulomatous disease, such as a fungal pathology. This report highlights the importance of persistence and a multimodal approach to the diagnosis of unidentified skin lesions, especially in the setting of failure to respond to standard therapies.</p>

A Rare Case of Infiltrative Cardiomyopathy: Diagnostic Dilemma

Presentation A 73-year-old white female with history of bilateral carpal tunnel syndrome, lumbar spinal stenosis, and family history of cardiomyopathy presented with worsening dyspnea on exertion. Exam showed right-sided crackles. There was no jugular venous distention, edema, macroglossia, or peri-orbital ecchymosis. Evaluation ECG demonstrated low voltage in all leads and no significant ST segment changes (Figure 1A). Labs showed undetectable troponin-I and normal NT-proBNP (119pg/mL). TTE revealed LVEF 55-65%, grade II diastolic dysfunction, thick and bright ventricular walls and global longitudinal strain of -17.9% with relative apical sparing (Figure 1B, Figure 1C). TTE findings raised concern for an infiltrative cardiomyopathy, specifically amyloidosis. Additional labs found polyclonal gammopathy on serum immunofixation with increased IgA (590mg/dL), kappa (20.4mg/L) and lambda (14.0mg/L). However, free kappa-to-lambda ratio (1.46) was normal. There was no monoclonal spike on urine immunofixation. Anti-neutrophil antibody screen was negative, and cobalt was undetectable. Ferritin (17ng/mL), C-reactive protein (0.8mg/L), and erythrocyte sedimentation rate (27mm/hr) were normal. Cardiac MRI found mild concentric left ventricular wall thickening up to 11 mm and late gadolinium enhancement throughout the myocardium (Figure 1D). Endomyocardial biopsy showed patchy fibrosis but no evidence of amyloidosis on Congo red staining. No granulomatous disease or inflammatory infiltrate was seen. Cutaneous nerve biopsy was also negative for amyloidosis. Technetium-99m pyrophosphate scan was negative for transthyretin amyloidosis with normal heart-to-lung ratio (1.3). Genetic testing for infiltrative cardiomyopathy genotypes revealed phenotypically silent heterozygosity for HFE hereditary hemochromatosis. Hereditary amyloidosis testing was negative. Follow-up Twelve-day ambulatory cardiac monitoring showed 11% PVC burden with multiple morphologies and three episodes of non-sustained VT. Amiodarone 200mg daily was initiated as opposed to therapeutic ablation due to multifocal nature of PVCs. The patient continued to have dyspnea on exertion but remained functionally independent. PET imaging was attempted, however the patient did not tolerate the dietary preparation. Conclusions A total evaluation is essential for infiltrative cardiomyopathy. History, exam, and preliminary testing in this case suggested cardiac amyloidosis; however, comprehensive evaluation could not support this diagnosis or an alternate mechanism. Despite diagnostic innovations including advanced cardiac imaging and genetic testing, the cause of infiltrative cardiomyopathy can remain obscure.

Human CD34+ Hematopoietic Stem Cell–Engrafted NSG Mice: Morphological and Immunophenotypic Features

Immunodeficient mice engrafted with human immune cells represent an innovative tool to improve translatability of animal models for the study of human diseases. Immunophenotyping in these mice focuses on engraftment rates and cellular differentiation in blood and secondary lymphoid organs, and is predominantly carried out by FACS (fluorescent activated cell sorting) analysis; information on the morphological aspects of engraftment and the prevalence of histologic lesions is limited. We histologically examined 3- to 6-month-old NSG mice, naïve or engrafted with CD34+ human hemopoietic stem cells (HSC), and employed a quantitative immunohistochemical approach to identify human and murine cell compartments, comparing the results with the FACS data. NSG mice mainly exhibited incidental findings in lungs, kidneys, testes, and adrenal glands. A 6-month-old NSG mouse had a mediastinal lymphoblastic lymphoma. The lymphoid organs of NSG mice lacked typical lymphoid tissue architecture but frequently exhibited small periarteriolar leukocyte clusters in the spleen. Mice engrafted with human HSC frequently showed nephropathy, ovarian atrophy, cataract, and abnormal retinal development, lesions considered secondary to irradiation. In addition, 20% exhibited multisystemic granulomatous inflammatory infiltrates, dominated by human macrophages and T cells, leading to the observed 7% mortality and morbidity. Immunophenotypic data revealed variable repopulation of lymphoid organs with hCD45+ human cells, which did not always parallel the engraftment levels measured via FACS. The study describes the most common pathological features in young NSG mice after human HSC engraftment. As some of these lesions contribute to morbidity, morphological assessment of the engraftment at tissue level might help improve immunophenotypic evaluations of this animal model.

ORAL MANIFESTATIONS IN DIFFERENT STAGES OF PARACOCCIDIOIDOMYCOSIS: A REPORT OF 2 CASES

Paracoccidioidomycosis is a systemic fungal infection that involves lungs and other organs. The objective is to report 2 cases at different stages of the disease and to emphasize the importance of the correct diagnosis. Middle-aged male patients sought assistance because they presented with pain in the palate. The first one also presented with weight loss, odynophagia, cough, cervical lymphadenomegaly, and reported pulmonary fibrosis. On intra-oral examination, both patients presented with a reddish lesion on hard palate with granulomatous surface and muriform aspect, and the first one also presented with lesions on the alveolar ridge and vestibule. Incisional biopsy was performed in both cases, and a chest radiograph was requested. In the first case lung involvement was observed. Histopathology showed intense granulomatous inflammatory infiltrate and numerous yeasts with positive staining for PAS and Grocott, confirming the diagnostic hypothesis of paracoccidioidomycosis. Itraconazole therapy was started, and total remission of the lesions was observed.

Bovine tuberculosis: diagnosis in dairy cattle through the association of analyzes

ABSTRACT: Tuberculosis is a chronic anthropozoonosis of worldwide occurrence, caused by the bacterium Mycobacterium tuberculosis and its variants. In Brazil, the National Program for the Control and Eradication of Brucellosis and Tuberculosis in cattle, is responsible for diagnosing and the correctly allocate positive animals, but there is still a lack of definitive diagnosis of the disease. This study described the use of five diagnostic tools that can be used, preferably together, for the confirmation of suspected cases. These tools included the clinical examination comparative cervical tuberculin test, macroscopic findings during the slaughtering and histopathology of the damaged tissues followed by histochemistry. We evaluated a total of 211 dairy cattle, where 15.1% (32/211) had classic clinical signs of bovine tuberculosis, 74 (35%) showed reactivity in the comparative cervical tuberculin test. Of the total number of animals, 141 (66.8%) were referred for sanitary slaughter due to legal and control issues in the outbreaks of the disease. In the follow-up of slaughtering and inspection of viscera and carcasses, 74 (52.5%) had macroscopic lesions compatible with bovine tuberculosis, while 67 (47.5%) showed no visible changes. During the inspection, fragments of lymph nodes and liver and lung parenchyma were collected from five cattle with macroscopic lesions and five with no lesions. The histopathological analysis showed numerous areas of caseous necrosis with or without central calcification and granulomatous inflammatory infiltrate. In the special staining of Ziehl-Neelsen, numerous acid-fast bacilli were evidenced in all cases.

Clinical-dermatological, histological abnormalities and prevalence of Trypanosoma caninum and Leishmania infantum in dogs from Midwest region of Brazil.

Leishmania infantum is a trypanosomatid that causes parasitic dermatopathy in dogs. Trypanosoma caninum is another trypanosomatid, which infects the skin of dogs, although cutaneous abnormalities are absent. This study aimed to investigate the occurrence of T. caninum infection and its associated cutaneous and histological changes and compare it with the occurrence of L. infantum infection in dogs. The study included 150 dogs, of which T. caninum infection was identified in 3 (2%) and L. infantum infection in 15 (10%) of them, with no association (p>0.05) of these infections with the breed, gender, age, or cutaneous abnormalities. The cutaneous abnormalities were based on 1 (4.8%) and 12 (57.1%) dogs infected by T. caninum and L. infantum, respectively. The dermatohistopathological abnormalities in the dogs infected with T. caninum included mild perivascular lymphohistioplasmacytic infiltrates in the clinically asymptomatic ones, while in those with dermatological abnormalities, acanthosis, epidermal orthokeratotic hyperkeratosis, melanomacrophages, and co-infection with Microsporum sp. and Trichophyton sp. were observed. InL. infantum infected, the histopathological findings included chronic granulomatous inflammatory infiltrates and structures compatible with amastigotes. Despite the low frequency of T. caninum infection, our findings suggest that this trypanosomatid, unlike L. infantum, does not cause any macroscopic skin abnormalities.

Xanthogranulomatous Pyelonephritis A Review and Update of the Literature

Xanthogranulomatous pyelonephritis (XGP) is a rare chronic destructive granulomatous inflammatory process that affects sporadically the parenchyma of the kidney and the disease tends to be associated in many cases with long-term urinary tract obstruction, urinary tract infection and also in cases with calculi within the kidney. XGP does affect females more commonly in comparison with males, it does affect all age groups including newly born up to the elderly. Majority of the patients tend to be symptomatic and some of the symptoms could include: pyrexia, flank / loin / abdominal pain, palpable mass in loin/abdomen/costovertebral region, weight loss, visible haematuria. There may be associated diabetes mellitus, obesity, or immune deficiency. There may be anaemia and leucocytosis upon blood tests. Urine cultures may grow Escherichia coli, or proteus but in other situations the urine culture could be negative. Ultrasound scan of renal tract, CT and MRI scan of abdomen and pelvis tend to be undertaken in the assessments of patients. CT scan has globally been the establishment of radiology imaging diagnosis. Radiology imaging may demonstrate focal or diffuse XGP but the diffuse form is more common. It may reveal multiple low-attenuated cystic masses in the kidney, calculi in the kidney, hydronephrosis / dilated calyces / bear’s paw appearance in some cases. Macroscopy examination of the specimen of the kidney would tend to show multiple yellow nodules around calyces, and the lesion may form a mass or be infiltrative. Pathology examination of specimens of XGP would tend to show granulomatous inflammatory infiltrate that consists of neutrophils, lymphocytes, plasma cells, xanthomatous histiocytes, as well as multi-nucleated giant cells. Immunohistochemistry staining may show positive staining for CD68. Some of the differential diagnoses include: clear cell carcinoma of the kidney, papillary renal cell carcinoma, sarcomatoid renal cell carcinoma, leiomyosarcoma, malakoplakia of kidney, megalocystic interstitial nephritis, and renal replacement lipomatosis. Majority of diffuse cases have been treated by nephrectomy and antibiotics and some focal cases have been treated by partial nephrectomy and antibiotics but on very rare occasions cases have been treated by drainage of the abscess with biopsy and in conjunction with antibiotics. Percutaneous nephrostomy has also been undertaken pre-operatively to decompress the kidney by draining the abscess in the occasional case.

Pneumonia by Cryptococcus neoformans in a goat in the Southern region of Brazil

ABSTRACT: This report describes the clinical, pathological, and molecular aspects of a pneumonia by Cryptococcus neoformans in a goat in the Southern region of Brazil. A goat with a history of prolonged transportation presented dyspnea, nasal discharge and cough, and was subjected to necropsy, histopathology, and mycological evaluation. Grossly, cranio-ventral pulmonary consolidation was observed, characterized by firm and grayish areas interspersed with dark red foci. Histopathology of the lungs showed areas of parenchymal necrosis, containing blastoconidia with a slightly basophilic central cell, surrounded by an unstained capsule. It was associated with moderate granulomatous inflammatory infiltrate and peripheral fibrosis. The capsule and fungus cell exhibited marked Alcian Blue and periodic acid-Schiff staining, respectively. Diagnosis of fungal pneumonia by C. neoformans was based on clinical, pathological, and molecular findings.

Cutaneous Granulomatosis: a Comprehensive Review.

Cutaneous granulomatosis is a heterogeneous group of diseases, characterized by a skin inflammatory reaction triggered by a wide variety of stimuli, including infections, foreign bodies, malignancy, metabolites, and chemicals. From a pathogenic point of view, they are divided into non-infectious and infectious granulomas. Pathophysiological mechanisms are still poorly understood. Non-infectious granulomatous skin diseases include granuloma annulare, necrobiosis lipoidica, rheumatic nodules, foreign body granulomas, cutaneous sarcoidosis, and interstitial granulomatous dermatitis. Necrobiosis lipoidica is more frequent in diabetic patients. Infectious granulomas of the skin are caused by mycobacteria, in particular Mycobacterium tuberculosis or atypical mycobacteria; parasites, such as Leishmania; or fungi. Pathogenic mechanisms of M. tuberculosis-related granuloma are discussed. From a clinical point of view, it is useful to divide cutaneous granulomatosis into localized and more disseminated forms, although this distinction can be sometimes artificial. Three types of localized granulomatous lesions can be distinguished: palisaded granulomas (granuloma annulare, necrobiosis lipoidica, and rheumatoid nodules), foreign body granulomas, and infectious granulomas, which are generally associated with localized infections. Disseminated cutaneous granulomas can be divided into infectious, in particular tuberculosis, and non-infectious forms, among which sarcoidosis and interstitial granulomatous dermatitis. From a histological point of view, the common denominator is the presence of a granulomatous inflammatory infiltrate in the dermis and/or hypodermis; this infiltrate is mainly composed of macrophages grouped into nodules having a nodular, palisaded or interstitial architecture. Finally, we propose which diagnostic procedure should be performed when facing a patient with a suspected cutaneous granulomatosis.

GRANULOMATOUS REACTION TO RED PIGMENT, AFTER PERMANENT DECORATIVE TATTOO – CLINICAL CASE

Tattoos have been used for over 2000 years. Nowadays, the frequency of tattoos has been growing, especially among young people. In many countries, more than 25% of the population has a tattoo. Lately, the medical world is trying to increase the awareness concerning tattoos and the multiple risks they carry, like allergic reactions, lichenoid reactions, sarcoidosis, scleroderma-like reactions, viral, bacterial and fungal infections, benign tumors, pseudolymphomas, chronic lymphoid hyperplasia. Rarely, malignant tumor can develop on the tattoo surface. Clinical case: A 25 year old male has been admitted in our clinic presenting infiltrative, erythematous, scaly plaques, with yellow crusts on the surface, placed on the left arm and right leg, on the surface of two tattoos, only on the areas with red pigment. The patient had these symptoms for over one year. The tattoos were made two years before coming to the hospital. The cutaneous lesions were surgically removed and a histopathological exam was performed, revealing chronic granulomatous inflammatory infiltrate, with giant cells and eosinophilic necrosis areas. Discussions: In order to make a tattoo, body artists use multiple pigments, by themselves or in different combinations. The red pigment used in tattoos can be organic (santal wood, Caesalpinia echinata – both vegetal dyes) or inorganic (cadmium, mercury, selenium, sienna, the last one is an iron hydrate). There are several cutaneous reactions to the pigments found in tattoos: inflammatory reactions, allergic reactions, granulomatous reactions, lichenoid reactions and pseudolymphomatous reactions. Conclusions: 1) The granulomatous reaction is a complication that occurs frequently after red pigment tattoos; and 2) The patients need to be thoroughly investigated in order to rule out a foreign body reaction, sarcoidosis, an infectious disease (tuberculosis, mycobacteria infections, leprosy, leishmaniasis, and fungal infections), granuloma annulare, and iatrogenic granulomatous disease after the use of ribavirin, interferon, anti-TNF alfa medication, ipilimumab. Key words: permanent tattoo, post-tattoo granulomatous reaction, red pigment. Cite this article : Virgil Patrascu, Bianca Adela Cismaru-Iancu, Raluca Niculina Ciurea. Granulomatous reaction to red pigment, after permanent decorative tattoo – clinical case. RoJCED 2017;4(4): 218-223. https://doi.org/10.26574/rojced.2017.4.4.218

Xanthogranulomatous Pyelonephritis: A Rare Presentation

Xanthogranulomatous pyelonephritis is an uncommon chronic destructive disease process of renal parenchyma, associated with recurrent urinary tract infection. It is seen predominantly in females with no age specificity. The most common symptoms are flank or abdominal pain, fever, palpable mass, and gross hematuria. The common laboratory findings are leukocytosis and anemia. Urine cultures most often reveal Escherichia coli and Proteus mirabilis. Computed tomography is the mainstay of diagnostic imaging for xanthogranulomatous pyelonephritis. Histologically, xanthogranulomatous pyelonephritis presents a granulomatous inflammatory infiltrate mainly composed of lymphocytes, plasma cells, foamy histiocytes, and multinucleated giant cells. The differential diagnosis includes clear cell renal cell carcinoma, sarcomatoid renal cell carcinoma, leiomyosarcoma, malakoplakia, tuberculosis, and interstitial nephritis. Treatment includes antibiotics and surgery. In this article, we report a case of xanthogranulomatous pyelonephritis in a 38-year-old male patient with recurrent urinary tract infection.

Secondary Granulomatous Cutaneous Involvement in Peripheral T-cell Lymphoma.

Dear Editor: A 40-year-old Korean man was referred to our department with a 1-month history of brownish macules and papules on the trunk, and a 10-day history of 2 walnut-sized brownish nodules on the left arm (Fig. 1). The patient had been experiencing persistent coughing for 1 month, and computed tomography of the chest revealed multiple reactive mediastinal lymph nodes. A skin biopsy examination of nodules on the left arm revealed small-to-medium-sized pleomorphic lymphocytes in the upper dermis, which were positive for cluster of differentiation CD3 and CD4, and negative for CD8, epidermotropism, and granuloma formation (Fig. 2). Some histiocytic cells were positive for CD68. A biopsy of the abdomen revealed epidermotropism and lymphocytes containing hyperchromatic and indented nuclei, but without granuloma formation. Molecular biological investigation of the skin biopsy samples showed monoclonal T-cell receptor-γ gene rearrangement. Bone marrow biopsy findings were normal, but positron emission tomography scanning showed multiple lymphadenopathies and testicular involvement. Biopsy of the testes showed T-cell lineage malignant lymphoma without granulomatous features. Based on the clinical, histological, and molecular genetic features, peripheral T-cell lymphoma, not otherwise specified, World Health Organization classification with secondary granulomatous cutaneous involvement, was diagnosed. Microbiological (bacterial, fungal, mycobacterial) studies could not detect any specific infectious agent. Sarcoidosis or pulmonary tuberculosis was not evident in the complete hematological, biochemical, and radiological examinations. The patient was treated with narrow band ultraviolet B phototherapy (twice a week, suberythemal dose) and systemic chemotherapy (cyclophosphamide, doxorubicin, vincristine, prednisolone). Fourteen days after the initial treatment, the macules on the abdomen subsided and the sizes of the two nodules on the left arm were reduced. Fig. 1 (A) A 2×2-cm-sized hyperpigmented nodule on the left arm. (B) Multiple miliary grain to rice-grain-sized erythematous to brownish macules and papules on the trunk. Fig. 2 (A) Dermal, perivascular nodular inflammatory cell infiltration. (B) Epidermotropism of lymphocytes, with hyperchromatic and indented nucleus. (C) Many histiocytes and atypical lymphocytes with hyperchromatic nuclei form sarcoid-like granuloma (HE ... Granuloma formation is rarely observed in secondary cutaneous lesions from T-cell lymphomas whose original lesions showed no granulomatous features. Granulomatous lymphomas (both primary and secondary) are reported to represent 1.6% of all lymphomas1,2,3. Sarcoid-like granulomas are most common, but tuberculoid, granuloma annulare-like, granulomatous rosacea, or granulomatous panniculitis types have also been reported2. In addition, various granulomatous patterns may coexist in the same patient1. The exact pathogenesis of secondary granulomatous cutaneous involvement in peripheral T-cell lymphoma remains unclear. It has been proposed that epithelioid cell reaction indicates secretion of chemotactic or migration-inhibiting lymphokines by the neoplastic T-cell, and these cytokines may in turn be responsible for attracting monocytes, thereby resulting in granuloma formation1. However, the prognostic value of this epithelioid response remains controversial. In contrast, some reports have suggested that granulomatous inflammation represents a host response against the tumor and may represent a good prognostic factor for the clinical behavior of cutaneous lymphoma4. However, because of the limited number of cases reported to date, determining a direct relationship between the presence of a granulomatous inflammatory infiltrate and the prognosis of secondary cutaneous lymphomas is difficult.

Adenovirus disease in six small bowel, kidney and heart transplant recipients; pathology and clinical outcome.

Adenoviruses are emerging as important viral pathogens in hematopoietic stem cell and solid organ transplant recipients, impacting morbidity, graft survival, and even mortality. The risk seems to be highest in allogeneic hematopoietic stem cell transplant recipients as well as heart, lung, and small bowel transplant recipients. Most of the adenovirus diseases develop in the first 6 months after transplantation, particularly in pediatric patients. Among abdominal organ recipients, small bowel grafts are most frequently affected, presumably due to the presence of a virus reservoir in the mucosa-associated lymphoid tissue. Management of these infections may be difficult and includes the reduction of immunosuppression, whenever possible, combined with antiviral therapy, if necessary. Therefore, an awareness of the pathology associated with such infections is important in order to allow early detection and specific treatment. We reviewed six transplant recipients (small bowel, kidney, and heart) with adenovirus graft involvement from two institutions. We sought to compare the diagnostic morphology and the clinical and laboratory findings. The histopathologic features of an adenovirus infection of the renal graft and one native kidney in a heart transplant recipient included a vaguely granulomatous mixed inflammatory infiltrate associated with rare cells showing a cytopathic effect (smudgy nuclei). A lymphocytic infiltrate, simulating T cell rejection, with admixture of eosinophils was also seen. In the small bowel grafts, there was a focal mixed inflammatory infiltrate with associated necrosis in addition to cytopathic effects. In the heart, allograft adenovirus infection was silent with no evidence of inflammatory changes. Immunohistochemical stain for adenovirus was positive in all grafts and in one native kidney. All patients were subsequently cleared of adenovirus infection, as evidenced by follow-up biopsies, with no loss of the grafts. Adenovirus infection can involve allografts as well as native organs in solid organ transplant recipients. Infection is associated with variable necrosis and acute inflammation, in addition to a rejection-like infiltrate. Hematuria in non-renal solid organ transplant recipients may be associated with adenovirus nephritis and clinically silent graft involvement. Prompt diagnosis (aided by immunohistochemistry (IHC) and serology), with specific treatment, can prevent graft loss.

Emphysematous Eosinophilic Lymphangitis in the Ruminal Submucosa of Cattle.

Twenty cattle (14 Holstein-Friesian, 3 Japanese Black, 3 Aberdeen Angus) ranging in age from 3 months to 8 years exhibited, at slaughter, emphysematous thickening of the ruminal submucosa owing to the appearance of numerous, contiguous, small gas bubbles. Microscopic changes in the ruminal submucosa consisted of (1) multiple cystic (emphysematous) lymphangiectasis that was frequently lined or occluded by granulomatous inflammatory infiltrates including macrophages, multinucleate giant cells, and eosinophils; (2) intralymphatic phagocytosis by macrophages and giant cells of eosinophils that showed positive labeling with the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling assay; and (3) an inflammatory infiltrate extending from the area of lymphangitis into surrounding tissue, as well as edema, hemorrhage, fibrin exudation, fibroplasia, or capillary proliferation throughout the lesional submucosa. In addition, 15 (75%) of the cattle had globular leukocyte infiltrates in the mucosal epithelia of the rumen.

Pheohyphomycotic cyst.

Sir, Pheohyphomycosis is an affection characterized by dematiaceous yeast-like cells, hyphae and pseudo-hyphae in the affected tissue.[1] It can occur in any climatic region, but it is more frequent in the tropics. The involvement of skin and subcutaneous tissue is known as subcutaneous pheohyphomycosis.[12] The term “phaeohyphomycosis” was coined by Ajello et al. in 1974.[3] These fungi often infect patients who are not overtly immunocompromised and therefore may be encountered in a wide variety of cases. A 60-year-old housewife presented to dermatology outpatient department of a tertiary care hospital with a smooth painless swelling on the dorsal aspect of left foot of two years duration. The patient gave a history of minor trauma to the involved foot with a wooden splinter while doing household chores two months prior to occurrence of lesions. There was no history of discharge from the swelling. Her medical history revealed that she was hypertensive and was suffering from degenerative joint disease limited to both the knees. Her general and systemic examination was remarkably normal. Complete haemogram, routine biochemistry, urinalysis, chest roentgenogram and cardiac evaluation were normal. The tuberculin skin test was negative. Cutaneous examination revealed a well-defined smooth swelling on the dorsum of left foot with intact overlying skin with a groove in between clinically looking like a loculated cystic swelling [Figure 1]. Radiological examination including ultrasound suggested a subcutaneous swelling without bony involvement. There was no evidence of lymphangitic spread or regional lymphadenopathy. Histopathological examination of biopsy from left foot swelling showed a cystic structure lined by a granulomatous inflammatory infiltrate. Culture from the tissue sample showed no growth on Sabourauds dextrose agar. Gomori Methenamine Silver (GMS) staining of biopsy tissue revealed multiple black staining hyphae with irregular branching [Figure 2]. Masson-Fontana staining showed multiple hyphae containing melanin, consistent with the diagnosis of pheohyphomycotic cyst. Species identification could not be done due to lack of resources at our end.Figure 1: A smooth lobulated swelling on the dorsum of left footFigure 2: Gomori Methenamine Silver stained section showing black staining hyphae with irregular branching along the cyst wall (×20)With a working diagnosis of pheohyphomycosis, the patient was started on oral saturated solution of potassium iodide in the concentration of 1 gm/ml along with itraconazole 200 mg twice daily along with monitoring of liver enzymes. The patient was lost to follow-up after three months of therapy due to personal difficulties. Phaeohyphomycosis is a rare infection caused by dematiaceous fungi, of which most commonly incriminated are Exophiala, Alternaria, Bipolaris, Wangiella, and Curvularia.[4] The clinical manifestations of pheohyphomycosis can be divided into four categories: (i) superficial form, including “black piedra” and “tinea nigra” representing infection of superficial layers of skin; (ii) cutaneous and corneal form, which includes dermatomycosis. onychomycosis and mycotic keratitis; (iii) subcutaneous form comprising of cystic lesions which usually follow after a traumatic event; (iv) systemic or invasive form, in which there is dissemination to other organs; this form occurs in immunocompromised patients and organs commonly involved include lungs, brain, paranasal sinuses and rarely, the skin.[5] Subcutaneous infection is caused by traumatic inoculation of the organisms and is usually observed in exposed areas of skin surface. Although diagnosis relies on culture of the organism or demonstration of pigmented hyphae in tissue biopsy, in some cases, cystic lesions are caused by nonpigmented hyphae and the condition is then termed as hyalohyphomycotic cyst.[2] In our patient, histopathology showed a cystic structure in the deep dermis and the wall of the cyst lined by a suppurative granulomatous infiltrate with multiple pigmented hyphae along the cyst wall. Hyphal elements could be clearly visualized on GMS staining. To differentiate from hyalohyphomycosis (nonpigmented hyphae), Masson-Fontana stain can be utilized to demonstrate pigment melanin in the fungus.[67] In our case both GMS stain and Masson-Fontana stain confirmed the diagnosis of phaeohyphomycosis. Subcutaneous disease can be managed by surgical excision which is the chief modality of treatment with or without antifungal therapy.[3] Nevertheless; itraconazole at a dose of 200 mg twice daily provided some respite from surgical management in an individual who was unwilling to tolerate extensive debulking surgery.[8]

Xanthogranulomatous hypophysitis: a rare and often mistaken pituitary lesion.

SummaryXanthogranulomatous hypophysitis (XGH) is a very rare form of pituitary hypophysitis that may present both clinically and radiologically as a neoplastic lesion. It may either be primary with an autoimmune aetiology and can occur in isolation or as a part of autoimmune systemic disease or secondary as a reactive degenerative response to an epithelial lesion (e.g. craniopharyngioma (CP), Rathke's cleft cyst, germinoma and pituitary adenomas) or as a part of a multiorgan systemic involvement such as tuberculosis, sarcoidosis or granulomatosis. It may also present with a variation of symptoms in children and adults. Our case series compares the paediatric and adult presentations of XGH and the differential diagnoses considered in one child and two adult patients, highlighting the wide spectrum of this condition. Endocrine investigations suggested panhypopituitarism in all three patients and imaging revealed a suprasellar mass compressing the optic chiasm suggestive of CP or Rathke's cleft cyst in one patient and non-functioning pituitary macroadenoma in two patients. Magnetic resonance imaging (MRI) demonstrated mixed signal intensities on T1- and T2-weighted sequences. Following endoscopic transsphenoidal surgery, histological analysis revealed necrotic material with a xanthogranulomatous reaction confirming XGH in two patients and a necrobiotic granulomatous chronic inflammatory infiltrate with neutrophils in one patient, which is not typical of current descriptions of this disorder. This case series describes the wide spectrum of XGH disease that is yet to be defined. Mixed signal intensities on T1- and T2-weighted MRI sequences may indicate XGH and diagnosis is confirmed by histology. Histological variation may indicate an underlying systemic process.Learning points XGH is a rare form of pituitary hypophysitis with a wide clinical and histological spectrum and can mimic a neoplastic lesion.XGH primarily presents with growth arrest in children and pubertal arrest in adolescents. In adults, the presentation may vary.A combination of hypopituitarism and mixed signal intensity lesion on MRI is suggestive of XGH and should be considered in the differential diagnosis of sellar lesions.Radical surgery is the treatment of choice and carries an excellent prognosis with no recurrence.

Sorting Out a Sore Spot.

A 6-year-old child living in Nebraska presented with a 6-month history of a sore on the left arm. Treatment with a 10-day course of oral cephalexin was unsuccessful, and the lesion gradually increased to the size of a quarter with mild itching and tenderness. The child was afebrile throughout the course and was able to pursue normal activities. On examination, the lesion was a shallow 2 × 2 cm moist ulcer with no bleeding, minimal tenderness, and a few tiny satellite lesions surrounding the ulcer (Figure 1A). There was no associated palpable lymphadenopathy. No other skin lesions or other abnormal findings were noted in physical examination. Skin (punch) biopsies were sent to the Centers for Disease Control and Prevention (CDC) for bacterial, mycobacterial, and fungal cultures. Histological sections stained with hematoxylin-eosin showed a hyperkeratotic epidermis in 1 biopsy and an ulcerated epidermis in another. A diffuse dense mixed granulomatous dermal inflammatory infiltrate of lymphocytes, histiocytes, plasma cells, neutrophils, and multinucleated giant cells was present throughout the biopsies (Figure 1B). Inflammation extended into the epidermis. Multiple intracellular oval 2–4 μm in size organisms were identified inside macrophages (Figure 2A) on high-power light microscopy. Giemsastained touch preparations demonstrated round to oval organisms measuring 2–4 μm with a 1 μm round nucleus and a smaller bar-shaped paranuclear kinetoplast (Figure 2B). A microbe was isolated in culture.