Cutaneous infections due to nontuberculous mycobacteria: histopathological review of 28 cases. Comparative study between lesions observed in immunosuppressed patients and normal hosts

To evaluate the histopathological features observed in patients with cutaneous infections due to nontuberculous mycobacteria (NTM) and to compare the histopathological patterns observed in immunosuppressed patients and normal hosts. Twenty-eight biopsy specimens corresponding to 27 patients with cutaneous infections due to NTM were reviewed. Eighteen biopsies corresponded to normal hosts (14 Mycobacterium marinum, 2 Mycobacterium chelonae, 1 Mycobacterium terrae and 1 Mycobacterium gordonae) and 10 biopsy specimens were obtained from 9 immunosuppressed patients (3 Mycobacterium chelonae, one of which had two biopsies, 1 Mycobacterium abscessus, 2 Mycobacterium kansasii, 1 Mycobacterium marinum, 1 Mycobacterium avium complex and 1 Mycobacterium simiae). A panel of histopathological features was evaluated by two independent observers in each biopsy specimen. Epidermal changes (acanthosis, pseudoepitheliomatous hyperplasia, exocytosis) were mainly observed in M. marinum infections. In immunosuppressed patients the infiltrate tended to be deeper, involving the subcutaneous tissue (100%) with a more diffuse distribution and constant abscess formation. A marked granulomatous inflammatory reaction was observed in 83% of immunocompetent and in 60% of immunosuppressed patients. In immunosuppressed patients a relationship between the chronic evolution of the disease and granuloma formation was demonstrated. A diffuse infiltrate of histiocytes with occasionally foamy appearance was noted in three biopsy specimens from three patients with AIDS. Acute and chronic panniculitis was detected in 8 biopsy specimens. In one biopsy (M. chelonae) an acute suppurative folliculitis was observed. Different histopathological patterns can be noted in biopsy specimens from cutaneous nontuberculous mycobacterial infections. The evolution of the disease and the immunologic status of the host may explain this spectrum of morphological changes. Tuberculoid, palisading and sarcoid-like granulomas, a diffuse infiltrate of histiocytic foamy cells, acute and chronic panniculitis, non-specific chronic inflammation, cutaneous abscesses, suppurative granulomas and necrotizing folliculitis can be detected. Suppurative granulomas are the most characteristic feature in skin biopsy specimens from cutaneous NTM infections. Some histopathological patterns seem more prevalent in immunosuppressed 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.     

Sea-urchin granuloma: histologic profile. A pathologic study of 50 biopsies

BACKGROUND: Sea-urchin granuloma is a chronic granulomatous skin lesion caused by injury with sea-urchin spines. Frequently these lesions occur on the hands and develop several months after the initial injury. Classified as an allergic foreign-body reaction, their most common histological pattern resembles sarcoid. The purpose of this study was to evaluate the light microscopic features of biopsies from lesions clinically diagnosed of sea-urchin granolomas. METHODS: We retrospectively reviewed 50 biopsy specimens corresponding to 35 patients with sea-urchin granulomas. These lesions were caused by injuries with the spines of the sea-urchin Paracentrotus lividus. Data were collected between 1990 and 1999 from patients in the seashore of Galicia (NW Atlantic coast, Spain). RESULTS: The cohort consisted of 35 patients (31 males, 4 females), with a median age of 35 years (range 14-60 years). The median duration of the disease was 7.5 months (range 2-60 months). We identified different histopathologic patterns. A granulomatous reaction was observed in 39 biopsies (78%). In 70% corresponding to 35 biopsies this granulomatous reaction was predominant. Foreign-body, sarcoidal, tuberculoid, necrobiotic and suppurative granulomas were identified. The remaining 15 biopsies (30%) showed a predominant inflammatory reaction with features of non-specific chronic inflammation or suppurative dermatitis. A panel of histopathologic features, including epidermal and dermal changes were evaluated. Presence of focal necrosis and microabscesses were common findings. In 50% of our specimens we found umbilication and/or perforation. Additional features included the presence of inclusion epidermoid cysts in four cases and squamous syringometaplasia in one case. CONCLUSIONS: Our observations suggest that sea-urchin granuloma span a wide morphologic spectrum. A granulomatous inflammatory reaction was predominant, with the foreign body and sarcoidal types the most frequent patterns. Other histopathologic patterns with non granulomatous inflammation can be noted. Some features, such as the frequency of perforation and the presence of necrobiotic granulomas have not previously been recognized in the literature.     

Non-infectious granulomatous dermatitis: a clinicopathological study

BACKGROUND: Granulomatous dermatitis frequently presents a diagnostic challenge to dermatopathologists because an identical histologic picture is produced by several causes, and conversely, a single cause may produce varied histologic patterns. METHODS: A retrospective analysis of skin biopsies received over a period of 7 years was performed, and cases of non-infectious granulomatous dermatitis diagnosed on histopathological examination were retrieved. RESULTS: Out of a total of 586 cases of granulomatous dermatitis, 71 cases (12.11%) were categorized as non-infectious granulomatous dermatitis on the basis of clinicopathological findings. Further subcategorization was done based on morphology of granulomas as epithelioid granulomas; 15 cases of sarcoidosis, 21.1%, one case of Crohn's vulvitis, 1.4%, necrobiotic granulomas; 11 cases of granuloma annulare, 15.4%, two cases of rheumatoid nodule, 2.8%, 10 cases of foreign body granulomas, 14.0%; 32 cases of miscellaneous group, 45%. CONCLUSIONS: Morphology alone is seldom specific and cannot be used as a diagnostic tool for identification of specific diseases. Adequate clinical data and work up in combination of pathological resources can help in elucidation of specific etiology of granulomatous dermatitis. Mohan H, Bal A, Dhami GP. Non-infectious granulomatous dermatitis: a clinicopathological study.     

Clinical spectrum and histological analysis of 32 cases of specific cutaneous sarcoidosis

BACKGROUND: Sarcoidosis is a multisystem granulomatous disorder of unknown aetiology in which skin involvement is frequent. OBJECTIVE: To review histological characteristics of biopsies of specific cutaneous lesions of sarcoidosis and their relationship with clinical course. PATIENTS AND METHODS: Biopsies from 32 patients with specific cutaneous sarcoidosis were reviewed. Histological findings and clinical characteristics of these patients were analysed. RESULTS: The initial clinical lesions of the patients were ten infiltrated nodule-plaques, eight papules, four maculopapular eruptions, five scar sarcoidosis, four subcutaneous nodules and one lupus pernio. Sarcoidal granulomas were located at dermis in 31 cases (74%) and at subcutaneous fat in 12 (28%) but only four were subcutaneous exclusively. Perivascular or periannexial distribution of granulomas was observed in eight cases (19%) and they had coalescence in 29 samples. The presence of foreign material was demonstrated in 11 cases (26%). CONCLUSIONS: Clinical spectrum of specific lesions of cutaneous sarcoidosis showed a good correlation with granulomas localization in the biopsies. However, traditional classification of specific cutaneous sarcoidosis is often overlapping. On the other hand, foreign bodies and other atypical histological findings were more common than initially expected.     

Cutaneous manifestations of infection by nontuberculous mycobacteria

Cutaneous infections by nontuberculous mycobacteria (NTM) are not usual but their relative importance has changed during the last few years and still further changes are expected. This study comprised 13 patients from whom NTM were recovered from skin biopsy specimens, sinus exudates or cutaneous abscesses. All samples were processed according to standard methods, and the isolates were identified by biochemical testing. Skin biopsy specimens, when available, were processed for histopathological study. The clinical records of the patients were reviewed, and the relevant clinical, microbiological and epidemiological data collected. The clinical manifestations were noted to be relatively nonspecific and consisted of draining sinuses, abscesses, ulcers and nodules with multicentric or sporotrichoid patterns. Tissue culture isolated Mycobacterium fortuitum complex in nine patients, M. avium in three, and M. marinum in one. In the nine patients studied by histopathology, various patterns were observed. These included dermo-hypodermal abscesses, suppurative granulomas, tuberculoid granulomas and granulomas with a perifollicular distribution. Cutaneous lesions can thus be the first and the only sign of NTM disease, and culture still remains the definitive diagnostic procedure.     

Role of Leishmania spp. infestation in nondiagnostic cutaneous granulomatous lesions: report of a series of patients from a Western Mediterranean area

Background  Leishmaniasis is a parasitic disease prevalent in countries of the Mediterranean area.
Objectives  The potential role of Leishmania as the aetiological factor for cutaneous granulomatous lesions in a series of patients from a Western Mediterranean area was evaluated. The practical usefulness of Leishmania -specific polymerase chain reaction (PCR) amplification and immunohistochemical techniques in skin biopsy specimens was assessed.
Methods  Twenty-five skin biopsies diagnosed as nonspecific granulomatous dermatoses were included in the study. A panel of histopathological features was blindly evaluated by two independent observers. Only those cases showing nondiagnostic clinicopathological features and lacking demonstrable microorganisms after bacteriological, mycological or mycobacteriological cultures and specific stains (Ziehl–Neelsen, Giemsa, Gram, periodic acid–Schiff stains) were finally selected. Quantitative real-time PCR was performed in all selected samples. In available samples, immunohistochemical detection of specific Leishmania spp. antigens was also performed.
Results  From the selected 25 biopsies, Leishmania spp. DNA was detected by real-time PCR in 13 cases. In seven of eight PCR-positive cases the presence of a varying density of amastigotes could also be demonstrated immunohistochemically.
Conclusions  Leishmania infection seems to be an important aetiological factor in cutaneous granulomatous lesions showing nondiagnostic features in endemic areas. In such areas, Leishmania -specific PCR amplification and/or immunohistochemical studies may be useful diagnostic tools. These techniques may be specifically indicated in the evaluation of patients showing nonspecific granulomatous inflammatory infiltrates of unknown aetiology lacking the histopathological evidence of parasites.     

Unusual histopathological features of cutaneous leishmaniasis identified by polymerase chain reaction specific for Leishmania on paraffin-embedded skin biopsies

BACKGROUND: Cutaneous leishmaniasis (CL) is rare in Northern Europe and may be overlooked because colleagues have little experience with it. OBJECTIVES: To identify manifestations of CL that may escape diagnosis. METHODS: Correlation of clinical diagnosis and histopathological findings in 28 biopsy specimens taken from 19 patients with CL confirmed by polymerase chain reaction (PCR) specific for Leishmania. RESULTS: In only one patient was the clinical diagnosis CL; other diagnoses included: malignant epithelial neoplasms (5), follicular cyst (2), atypical mycobacteriosis (1), sarcoidosis (2) and lymphoma (1). Lesions were single (15) or few (4) nodules predominantly situated on the extremities or face (16). Histopathological findings were diagnostic of CL in only 10 cases. In nine cases Leishmania was not identified microscopically; histopathological diagnoses were: granulomatous dermatitis (6), lupoid rosacea (1), foreign body granuloma (1) and granuloma annulare (1). Unaltered epidermis (9), nodular infiltrates (5), numerous multinucleated histiocytes (3), palisaded granulomas with fibrinoid centres (2), sarcoidal granulomas (4) and elastophagocytosis (1) misled the histopathologists in these cases. CONCLUSIONS: CL seems often to be misdiagnosed clinically in countries where it is not endemic. Histopathologically, CL may be misinterpreted as sarcoidosis, foreign body granuloma, lupoid rosacea and granuloma annulare, especially when Leishmania is not seen microscopically. We suggest that in Northern Europe, PCR for Leishmania-specific DNA should be performed routinely in any granulomatous dermatitis presenting as a single or few nodules on the extremities or face, even when a diagnosis of CL was not considered by the referring clinician.     

Erythema induratum (nodular vasculitis) associated with Crohn's disease: a rare type of metastatic Crohn's disease

We herein report a patient with erythema induratum/nodular vasculitis (EI/NV) associated with Crohn's disease (CD), which is considered to be a rare type of metastatic CD. A 54-year-old woman, who had a history of CD, presented with erythematous nodules on her legs. The histopathological features of the skin biopsy revealed a granulomatous, mixed septal and lobular panniculitis, which was characterized by many discrete epithelioid cell granulomas (necrobiotic/necrotizing-type and sarcoidal type), necrosis of the adipocytes, and granulomatous phlebitis in the muscular wall of a subcutaneous vein. A review of the pertinent literature and the presented case suggested the following: (1) panniculitis associated with CD may be either an erythema nodosum type or an EI/NV type; (2) so far, the reported cases of metastatic CD or granulomatous vasculitis in CD rarely presented with granulomatous panniculitis without dermal involvement, and most cases showed histopathological features that were similar to or indistinguishable from those of EI/NV; and (3) the finding of granulomatous vasculitis (especially the presence of discrete epithelioid cell granulomas involving the veins or venules) may be a characteristic feature of EI/NV associated with CD, in contrast to the finding of acute vasculitis, which is typically present in patients with EI/NV due to causative factors other than CD.     

Histopathologic features of superficial granulomatous pyoderma

Study of the histopathologic pattern of 28 cases of superficial granulomatous pyoderma demonstrated an ulcerative, verrucous pyoderma of the superficial dermis. Focal abscesses in the subepidermis or dermis were juxtaposed with granuloma formation and plasma cell inflammation. Hemorrhage and granulation tissue were present. The clinical lesions are indolent, and this feature is confirmed by chronic inflammatory elements, including sinus tract formation and focal fibrosis. Superficial granulomatous pyoderma must be added to the histologic differential diagnosis of the vegetative and ulcerative granulomas: blastomycosis, tuberculosis verrucosa cutis, and bromoderma.     

Sarcoidosis with small syringotropic granulomas presenting clinically as a pigmented purpuric dermatosis: Inconspicuous clinical and histopathological clues to systemic illness

Sarcoidosis is a multisystem granulomatous disease with a myriad of clinical manifestations and a predilection to involve the lungs, eyes, lymph nodes, and skin. A 38-year-old man presented to dermatology with a history of progressive dyspnea, pulmonary consolidations on chest X-ray, and hilar adenopathy on computed tomography scan. Skin exam revealed asymptomatic, yellow to brown macules on the right lower extremity. Biopsy of a lesion showed diminutive syringotropic granulomas and perivascular hemosiderin; stains for bacteria, mycobacteria, and fungi were negative. Subsequent fine needle aspiration of a hilar mass revealed non-necrotizing epithelioid granulomas further supporting a diagnosis of sarcoidosis. The patient was placed on systemic steroids and had improvement of his pulmonary symptoms and stabilization of his hilar lymphadenopathy without resolution of his pigmented purpuric dermatosis (PPD) like lesions. Only three prior cases of syringotropic sarcoidosis have been reported; however, the biopsies had revealed conspicuously large granulomas in contrast with the small granulomas in our case, and none of the prior patients had clinical examination findings that mimicked PPD. Recognition of rare dermatologic and histopathological appearances of sarcoidosis is paramount as cutaneous sarcoidosis may be the harbinger of a systemic illness, which requires a timely diagnosis.     

Peripheral T-cell lymphoma with secondary epithelioid granulomatous cutaneous involvement: a clinicopathologic study of four cases

Epithelioid granuloma formation has rarely been observed in specific cutaneous lesions from T-cell lymphomas other than those of mycosis fungoides/Sézary syndrome (MF/SS). Three patients diagnosed with nodal and/or extranodal (tonsillar) non-Hodgkin's peripheral T-cell lymphoma (PTCL) and one patient with angioimmunoblastic T-cell lymphoma (AILD), developed specific cutaneous involvement showing prominent epithelioid cell and/or granulomatous inflammation. The original diagnostic lesions had no granulomatous features. In addition to a specific lymphomatous infiltrate, prominent dermal and/or subcutaneous granulomatous infiltrates were observed. Sarcoid-like granulomas were observed in two patients (one of them presented a granuloma annulare-like pattern in early lesions), granulomatous panniculitis was noted in one patient and in one patient with AILD, masses of epithelioid cells were noted. The clinicopathological features of cutaneous involvement by PTCL showing a florid epithelioid and/or granulomatous cell reaction are reviewed. Various histopathological patterns can be observed. The diagnostic difficulties of these cases are stressed.     

Melanocytic matricoma: two cases of a rare entity in women

Melanocytic matricoma is a rare cutaneous adnexal tumor occurring in humans with only 13 cases reported in the literature. The typical lesion is a circumscribed pigmented nodule on sun‐damaged skin. Most cases have occurred in elderly men. The tumor contains a mixed population of matrical cells, supramatrical cells, shadow or ghost cells, and dendritic melanocytes. We report two cases of melanocytic matricoma in two elderly women with unusual histopathological features such as cystic degeneration and focal granulomatous inflammation, which are considered to be atypical for this entity.     

High prevalence of 'Borrelia-like' organisms in skin biopsies of sarcoidosis patients from Western Austria

Background: Sarcoidosis is a multisystem granulomatous disorder of unknown aetiology with frequent skin involvement.
Objective: To investigate the frequency of 'Borrelia-like' organisms in cutaneous sarcoidosis (CS) by focus-floating microscopy (FFM).
Methods: Retrospective analysis of 38 CS specimens by immunohistochemistry with polyclonal anti-Borrelia antibody and assessment by FFM.
Results: Specimens of 34.2% CS were positive for 'Borrelia-like' organisms by FFM. Usually single spirochetes, rarely pairs or small clusters of bacteria were observed between collagen bundles or at the periphery of granulomas. Polymerase chain reaction (PCR) was performed in addition in 11 cases and was negative in all biopsies.
Samples of erythema migrans served as positive controls: 92.3% of 39 samples were positive by FFM, but only 46.6% gave positive results by PCR. Of 61 negative controls only one specimen was falsely positive by immunohistochemistry.
Conclusion: Detection of 'Borrelia-like' organisms by FFM in tissue sections of CS underlines the possibility that such microorganism may be involved in the pathogenesis of some cases of CS.     

Verrucous ulcerative skin lesions in sarcoidosis. An unusual clinical presentation.

A twenty-seven year old man with a two year history of sarcoidosis and systemic manifestations of this disease along with verrucous ulcerative skin lesions is presented. Biopsy specimens of the cutaneous lesions showed typical noncaseating granulomas as well as necrotizing granulomatous inflammation. After other possible etiologies were excluded, prednisone therapy was instituted with prompt resolution of the skin lesions, leaving atrophic scars.     

Cutaneous leishmaniasis mimicking inflammatory and neoplastic processes: a clinical, histopathological and molecular study of 57 cases

Background: Cutaneous leishmaniasis displays considerable variation in its histopathological and clinical presentation. Clinically, it progresses from a papule into a painless ulcerated and crusted nodule/papule. Microscopically, it progresses from sheets of amastigote‐filled histiocytes to granulomatous inflammation. Methods: The study was conducted on 145 skin biopsies from untreated patients with histopathological and/or clinical suspicion of cutaneous leishmaniasis in Lebanon, Syria and Saudi Arabia (1992–2010). The pre‐biopsy clinical diagnosis and demographic data were collected. Biopsies were evaluated for the major microscopic pattern, and the parasitic index (PI) was also determined. Diagnosis was confirmed by polymerase chain reaction (PCR) followed by molecular sub‐speciation. Results: Of the 145 patients, 125 were confirmed as cutaneous leishmaniasis by PCR. Eighteen cases presented with a pre‐biopsy clinical diagnosis other than cutaneous leishmaniasis that ranged from dermatitis to neoplasm. Of the 125 cases, 57 showed a major histopathological pattern other than cutaneous leishmaniasis. Identification of amastigotes was equivocal (PI ≤1) in 38 of the 57 cases. Of interest, all the 18 cases with a pre‐biopsy clinical diagnosis other than cutaneous leishmaniasis also showed atypical histopathology for cutaneous leishmaniasis. Conclusions: The manifestations of cutaneous leishmaniasis are broad and may mimic other inflammatory and neoplastic diseases. Pathologists and dermatologists should be aware of such pitfalls and can utilize PCR to confirm the diagnosis of leishmaniasis. Saab J, Fedda F, Khattab R, Yahya L, Loya A, Satti M, A‐G Kibbi, Houreih MA, Raslan W, El‐Sabban M, Khalifeh I. Cutaneous leishmaniasis mimicking inflammatory and neoplastic processes: a clinical, histopathological and molecular study of 57 cases.     

Lethal T- and NK-cell lymphomas mimicking granulomatous panniculitidies: a clinicopathologic study of three cases

An infiltrate mimicking subcutaneous panniculitis associated with a granulomatous response represents an uncommon histopathologic presentation of lymphoma. We report three cases, comprising one case each of nasal-type extranodal NK/T-cell lymphoma, cutaneous γ/δ T-cell lymphoma and human T-lymphotropic virus-I associated adult T-cell leukemia/lymphoma, which based on initial histopathologic and/or clinical presentation were thought to represent systemic lupus erythematosus, sarcoidosis and psoriasiform dermatitis, respectively. Excisional biopsies of indurated lesions performed at our institute; however, in each case showed an atypical subcutaneous lymphohistiocytic infiltrate associated with a variable number of granulomas. Extensive immunophenotypic characterization, in conjunction with histomorphologic and molecular analysis, established the diagnosis of lymphoma in all instances. All patients had a rapidly progressive clinical course and death was attributable to complications of lymphoma shortly after diagnosis. These cases highlight the importance of using a multimodality diagnostic approach to distinguish lymphomas masquerading as granulomatous panniculitis from inflammatory or reactive disorders associated with such histopathologic patterns.     

Cutaneous granulomatous vasculitis: its relationship to systemic disease

Microscopic and medical review of twenty-six patients with skin biopsy specimens that showed granulomatous vasculitis demonstrated vascular histiocytic granulomas with fibrinoid destruction of blood vessels in the dermis and panniculus. Cultures of the biopsy specimens were nonspecific. The skin lesions varied from erythema to papulonodular and vesicular eruptions; they were usually on the extremities but also involved the trunk. Eight patients had systemic lymphoproliferative diseases: three, lymphoma; two, angioimmunoblastic lymphadenopathy; two, preleukemia; and one, chronic granulocytic leukemia. Five of these eight patients died within 2 years after the onset of skin lesions. The four patients with systemic vasculitis died within 1 year after the onset of skin lesions. Five patients with arthritis, four with gastrointestinal disease, three with systemic sarcoidosis or sarcoidlike disease, and one with tuberculosis had a more favorable prognosis. The histologic pattern of cutaneous nonlymphomatoid granulomatous vasculitis is associated with significant systemic disease, especially lymphoproliferative disorders. Patients with lymphoproliferative disorders or systemic vasculitis have a much poorer prognosis than those with inflammatory or infectious granulomatous disease.