The dilemma of midline destructive lesions: a case series and diagnostic review.

BACKGROUND: Midline destructive lesions (MDLs) of the nose are a diagnostic dilemma due to an extensive differential diagnosis and vague presenting signs and symptoms. Etiologies may be neoplastic, autoimmune, traumatic, infectious, or unknown. STUDY DESIGN: Case series and review of the literature were done. METHODS: Medical records of 8 patients presenting with an MDL were reviewed. RESULTS: Each patient received nasal endoscopy, computed tomography scan of the sinuses, laboratory workup, culture (aerobes, anaerobes, fungus, and acid-fast bacilli), and biopsy with flow cytometry. Laboratory tests included complete blood count, basic metabolic panel, erythrocyte sedimentation rate, angiotensin-converting enzyme, antineutrophil antibodies, rheumatoid factor, anti-Ro and anti-La antibodies, Epstein-Barr virus antibodies, coccidiomycosis serology, HIV antibodies, fluorescent treponemal antibody absorption, classic antineutrophil cytoplasmic antibodies, perinuclear antineutrophil cytoplasmic antibody, proteinase 3, and myeloperoxidase. Choice of diagnostic study was individualized for each patient. Two patients were diagnosed with natural killer/T-cell lymphoma, 2 were diagnosed with Wegener's granulomatosis, and 4 remained idiopathic, despite the extensive workup. A diagnostic algorithm to aid in the approach to MDLs is presented. CONCLUSIONS: The diagnosis of MDLs remains difficult but is aided by a systematic approach and familiarity with multiple diagnostic techniques. It is imperative to take multiple tissue specimens from various sites, send them fresh, and communicate suspicion of lymphoma. Despite diagnostic advances and improved understanding of the diseases underlying MDLs, an etiology is often not identified.

Cocaïne et lésions destructrices centro-faciales : à propos d'un cas.

INTRODUCTION: Cocaine use is associated with multiple complications, some of which can mimic systemic diseases, especially Antineutrophil Cytoplasmic Antibody (ANCA) associated vasculitis. We report a case of Cocaine Induced Midline Destructive Lesions (CIMDL) for which a diagnosis of granulomatosis with polyangiitis (GPA) was discussed. CASE REPORT: A 42-year-old male, cocaine consumer, was admitted in our department for a centrofacial destructive process. He had no extra ear, nose and throat (ENT) involvement. ANCA were positive with a perinuclear fluorescence pattern and an anti-Proteinase 3 specificity. Regarding this unusual immunologic pattern and in the absence of histological argument for a GPA, a diagnosis of CIMDL was made. CONCLUSION: CIMDL is a centrofacial destructive process due to intranasal cocaine use. It is frequently associated with the presence of p-ANCA with both anti-HNE and anti-PR3 specificity.

Cocaine-induced midline destructive lesions mimicking ENT-limited Wegener's granulomatosis.

The prevalence of cocaine use is rising worldwide, with a resultant rise in associated pathology. Regular nasal use can cause cocaine-induced midline destructive lesions (CIMDL), which can be difficult to distinguish from ear, nose, and throat (ENT)-limited Wegener's granulomatosis (WG). Two cocaine users presented with mid-facial pain, epistaxis, and systemic symptoms. Both had nasal septal perforation, necrosis of sinus mucosa, and positive anti-neutrophil cytoplasmic antibodies (ANCA). Histology was inconclusive and treatment with immunosuppressive drugs was commenced. The first patient continued to use cocaine initially, with improvement in her symptoms only on high doses of steroid. Later she stopped cocaine and this plus a switch from cyclophosphamide to mycophenolate mofetil resulted in successful symptom resolution and steroid withdrawal. The second patient denied cocaine use but having only partially responded to high-dose prednisolone and methotrexate, she admitted continued cocaine use and was lost to follow-up. Evaluation of a patient with destructive lesions of the mid-face should include enquiry about intranasal use of cocaine. Localized ENT involvement, inconsistent ANCA pattern, and atypical biopsy findings for WG should be recognized as features of CIMDL. Although cessation of cocaine use is crucial, there may be a role for immunosuppression.

[Brownish plaques on both sides of the nose]. / Bräunliche Plaques an beiden Nasenseiten.

Granuloma fissuratum (Gf) is painful granular tissue caused by constant pressure exerted by glasses. The differential diagnosis includes further granulomatous dermatoses such as cutaneous sarcoidosis, mycobacterioses and autoimmune diseases. It is also important to rule out a basal cell carcinoma. The simplest and most effective treatment of Gf is to correct the glasses frame or, even better, to avoid wearing glasses to correct eyesight. Topical antiseptic/antibiotic treatment is recommended for superinfected lesions. The Gf usually heals within 1-6 months after correction of the glasses. If the lesion does not heal on its own, complete excision is recommended.

Erythematous indurated swelling on nose and upper lip. Cutaneous T cell lymphoma.

A 40-year-old man presented for diagnosis with nodules and plaques of the nose and upper lip, progessive over 1(1/2) years.

Idiopathic midline destructive disease: fact or fiction.

The differential diagnosis of a progressive destructive lesion of the midface and upper airway region includes both neoplastic and non-neoplastic entities; of these, the majority of cases prove to be either Wegener's granulomatosis or lymphoma. Historically, these sorts of necrotizing midfacial lesions were diagnosed clinically, and as a consequence a variety of overlapping categories of disease sprang up. As pathologic examination of biopsy material became both more widespread and (particularly in the last several years) more sophisticated, many lesions previously thought to be of mysterious origins have proven to be examples of lymphoma (in particular, sinonasal natural killer cell or T cell [NK/T] lymphomas). At present, the evaluation of a patient with a progressive destructive process involving the midface region should include imaging studies (to delineate the extent of disease) as well as biopsy (with sampling of lesional tissue for application of sophisticated testing--including immunohistochemical studies, flow cytometry, or molecular studies as necessary--to exclude the possibility of a NK/T cell lymphoma). There remain occasional patients whose necrotizing midfacial lesions continue to be difficult to classify despite the application of extensive testing; such patients are sometimes described as suffering from the nebulous entity of "idiopathic midline destructive disease". While it remains to be seen whether such patients will ultimately be assigned to other diagnostic groups (as, for example, occult toxic injuries--as in the case of cocaine abusers who are not forthcoming with regard to their drug usage), it seems likely that "idiopathic midline destructive disease" is a diagnostic term of questionable validity which should be used only with extreme reticence in modern practice.

Nasal NK/T-cell lymphoma causing diagnostic difficulties.

We present history, clinical presentation and anatomo-pathologic findings of a 24-year-old female patient with a nasal NK/T-cell lymphoma. This rare tumor is characterized by its angiocentric and angiodestructive growth, which results in extensive tumor necrosis. At the first encounter this tumor necrosis made it difficult to identify the nature of the tumor cells. However, this necrosis is a key feature: it is the result of the capacity of neoplastic NK/T-cells to invade vessels. The T-cell character of the neoplastic lymphoid has been shown by immunohistochemitry.

Centrofacial malignant granulomas. Clinicopathologic study of 40 cases and review of the literature.

An important problem in the treatment of centrofacial ulcerations is to establish a precise diagnosis, since similar clinical and microscopic findings can result from many different causes (as in the centrofacial malignant granuloma syndrome [CFMG]). A comprehensive surgical biopsy protocol (known as SNFMI/GMCF), involving microbiology, parasitology, immunology and pathology laboratories, allowed us to evaluate and to treat 40 cases of CFMG, who form the basis of this report. In 13 of them, specific diagnoses were found and curative treatments could be given. In the remaining 27, the optical microscopy pattern met the criteria for CFMG without identifiable origin or the presence of so-called lethal midline granulomas; however, a more precise evaluation with the help of immunofluorescence studies led to the recognition of malignant lymphoma (ulcerative lymphoma of the midface [ULM]). Most of these lymphomas belonged to the T cell lineage; the others were of B lymphoid origin, or, more rarely, of histiocytic origin. Patients with ULM received radiotherapy and chemotherapy with a response rate of 70.3%; however, the toxicity was significant, with frequent occurrence of chemotherapy-induced neutropenia followed by severe infectious facial cellulitis. Six patients were enrolled in a preliminary open trial of treatment with recombinant alpha-2b interferon with little success. Three patients were treated with radiation therapy only, and survived. Thus, CFMG is a syndrome with specific causes and treatments, requiring multiple extensive biopsies to make the correct diagnosis. The recognition of ULM as the cause of the previously called "lethal midline granulomas" leads logically to the use of chemotherapy with growth factors in order to ameliorate its bad prognosis.

Imported mucocutaneous leishmaniasis in New York City. Report of a patient treated with amphotericin B.

A case of mococutaneous leishmaniasis in a patient referred to Memorial Sloan-Kettering Cancer Center, New York, with a presumptive diagnosis of lethal mid-line granuloma is described. The patient had lived in Bolivia and had been treated with antimony during and after which his mucosal lesions progressed. These lesions completely healed with 971 mg of amphotericin B. Mucocutaneous leishmaniasis is endemic in many areas of Central and South America and may occur in patients in the United States who have lived in or traveled to these areas. Organisms may be difficult to identify, and multiple biopsies and cultures may be necessary. The use of amphotericin B for the treatment of leishmaniasis is reviewed. It is an effective alternative to antimony therapy, and in some cases resistant to antimony, it may be the drug of choice.

Midline granuloma syndrome: a clinicopathologic study of 13 patients.

Thirteen patients with the clinical features of the midline granuloma syndrome are reported. Seven of the patients were determined to have Wegener's granulomatosis and had segmental necrotizing glomerulonephritis in their renal biopsies. Eighteen upper aerodigestive trace mucosal biopsies were available for review from the seven patients, and nine of these biopsies had a granulomatous angiodestructive inflammatory cell infiltrate considered "diagnostic" of Wegener's granulomatosis. The remaining nine biopsies lacked the specific histologic features of Wegener's granulomatosis but were considered consistent with mucosal involvement by the disease. Five of the remaining six patients had upper aerodigestive tract biopsies that were characterized by lymphocytic infiltrates. Three of the five patients had appreciable numbers of "atypical" cells in their biopsies and presented with radiologic evidence of lung involvement. It is our impression that patients with "significant cellular atypia" in their lymphocytic infiltrates have a disease indistinguishable from lymphomatoid granulomatosis, and these patients have a high propensity for either the presence or development of systematic disease that may require chemotherapy. Two patients had lymphocytic infiltrates with only minor degrees of cytologic atypia and no evidence of multisystem disease, and both of these patients responded to local radiation therapy. The remaining patient had a nonspecific histologic pattern in her numerous biopsies and was diagnosed as idiopathic midline destructive disease. She also had an adequate response to radiation therapy.

Idiopathic midline destructive disease (IMDD): a subgroup of patients with the "midline granuloma" syndrome.

"Midline granuloma syndrome" encompasses a number of specific clinicopathologic entities, such as "Wegener's granulomatosis, midline malignant reticulosis, lymphoma, nasal carcinoma and a broad spectrum of infectious diseases. In the course of studying a number of patients presenting with destructive lesions of the upper respiratory tract, 11 cases emerged as having unique clinicopathologic features. These are: 1) presence of locally destructive lesions which are always restricted to the upper respiratory tract. 2) Absence of systemic disease during a follow-up period of six months to 18 years (mean 7.3 years). On examination of repeated biopsy specimens the histopathologic picture consisted of acute and chronic inflammation with variable amounts of necrosis. Granulomata were seen in one case. Malignant or atypical cells were invariably absent. Frank vasculitis was not seen, although in five of the patients inflammatory cells in the wall of small vessels were conspicuous 4) Inability to demonstrate an infectious origin by culture or special stains. Radiation therapy has proven effective in patients with this entity, for which the term "Idiopathic Midline Destructive Disease" (IMDD) is proposed.

Biopsy findings in malignant histiocytosis presenting as lethal midline granuloma.

Nasal biopsy findings in malignant histiocytosis presenting clinically as lethal midline granuloma are characterised by necrosis and infiltration of atypical histiocytic cells with a diffuse positive reaction for non-specific esterase. This cellular character was common to midline malignant reticulosis, and midline malignant reticulosis and malignant histiocytosis are thought to be the same disease. Patterns of histiocytic infiltration in the nasal lesions of 19 cases are reported in this paper. Polymorphic and monomorphic patterns were observed in 11 and four cases respectively, on the initial biopsy, but subsequently the infiltrates frequently became monomorphic on serial biopsy. The reverse was not observed. Surface marker and cytochemical studies showed the true histiocytic nature of the proliferating cells, and necropsy findings justified the diagnosis of malignant histiocytosis.

Wegener's granulomatosis and midline (nonhealing) "granuloma".

There has been considerable controversy over the years regarding the distinctions between various disorders characterized by a necrotizing and granulomatous inflammation of the tissues of the upper respiratory tract and oral cavity. It now seems clear that if infections and other known agents can be excluded, three clinicopathologic entities remain: Wegener's granulomatosis (a systemic disease), idiopathic midline (nonhealing) granuloma, and premalignant or malignant lymphoreticular lesions. The antigenic stimulus for all three may be related but remains unidentified.

Midline granuloma.

A 34-year-old woman had a granulomatous ulceration of the nose that responded to radiation therapy. The limitation of the disease to the nose and the histologic findings were consistent with a diagnosis of midline granuloma, Stewart type. The relationship of midline granuloma to Wegener's granulomatosis is reviewed. In view of the uniform mortality that accompanies untreated midline granuloma, a correct diagnosis must be made so that radiation therapy can be promptly instituted.

The protean clinical features of polymorphic reticulosis (lethal midline granuloma).

Confusion surrounds the entity known as "lethal midline granuloma". Partly responsible is the lack of specificity in this term. "Polymorphic reticulosis" has been used as a term to describe the morphology of the disease. Thirty-two cases illustrate the protean features of this disease. Although it commonly presents in the head and neck, other sites such as the lungs, kidneys, skin, and gastrointestinal tract may be involved, either alone or in conjunction with lesions of the head and neck. Clinically, it is easily confused with Wegener's granulomatosis. Histopathologic differentiation, however, is both feasible and important. Wegener's granulomatosis is treatable with steroids with or without cyclophosphamide; polymorphic reticulosis confined to one site responds to irradiation. In polymorphic reticulosis, thhe best results of treatment are obtained in localized lesions of the upper airway treated early with irradiation; a poorer outcome is associated with multifocal involvement, which necessitates systemic therapy.

Dilemmas in the management of chronic nasal and sinus inflammatory diseases of unknown etiology.

The diagnostic criteria and therapeutic regimens for upper airway necrotizing diseases such as Wegener's granulomatosis, polymorphic reticulosis, and the recently described idiopathic midline destructive disease have been better defined and clarified in the past decades. Despite an improved understanding of the various disease processes, there continues to be difficulty in establishing an early diagnosis before proceeding with prompt treatment to minimize loss of function and cosmetic deformity. To achieve these goals, we have expanded the indications for the use of the cytotoxic drug, cyclophosphamide, in those patients whose clinical and histologic presentations are suggestive of Wegener's granulomatosis, but in whom a specific diagnosis has not been confirmed by biopsy specimen. We have seen ten patients with upper airway lesions of a chronic inflammatory nature over the past six years at the Medical College of Wisconsin affiliated hospitals. Only three of these have had a definitive histopathologic diagnosis of Wegener's granulomatosis made prior to the initiation of cytotoxic therapy. Six have undergone treatment under our expanded criteria without a prior definitive diagnosis. Five of these have had arrest of the disease process, and one has had no response to therapy. One patient was not treated. There have been no serious side-effects from cyclophosphamide therapy in these patients.

Malignant histiocytosis presenting as lethal midline granuloma.

The clinical and histologic materials, including autopsy findings, from 6 cases with clinical features of so-called lethal midline granuloma were examined. These cases were selected by characteristic biopsy findings observed in the nasal lesions. The histologic features of the nasal lesions were necrosis and infiltration of atypical histiocytic cells. The mean age was 37 years with a 2:1 male to female preponderance. Nasal complaints and fever were frequent manifestation, and physical findings showed necrotic, granulomatous lesions in the nasal cavity in all cases. The survival ranged from 4 to 24 months, giving a mean value of 13 months. Autopsy findings revealed systemic, neoplastic proliferation of atypical histiocytes, from these observation, these 6 cases should be regarded as malignant histiocytosis (MH) with usual presentation.

Malignant lymphoma in the nose. Clinicopathological differences from the malignant histiocytosis presenting as lethal midline granuloma.

The clinical records and histologic materials from 7 cases with malignant lymphoma (ML) in the nose were examined, and the results were compared to those in malignant histiocytosis (MH) presenting as lethal midline granuloma previously reported by us. The main differences in the clinical findings were 1) younger initiation of the disease in MH than in ML (mean values were 56 and 37 years of age, respectively); 2) ML showed a polypoid nasal mass with necrosis but MH showed necrotic granulomatous lesions; and 3) much better survival in ML than in MH. The histological findings of malignant lymphoma differed from malignant histiocytosis not only in monotony but also in cytologic details. Alpha-naphthyl acetate and butyrate esterase reactions gave clear distinction between the two diseases. From these findings, we conclude that malignant lymphoma should be clinicopathologically separated from malignant histiocytosis.

Current concepts of the lethal midline granuloma syndrome.

"Lethal midline granuloma" is an unusual but devastating spectrum of lymphoproliferative disorders that is now thought to include four entities: idiopathic midline destructive disease, Wegener's granulomatosis, polymorphic reticulosis, and nasal lymphoma. These disorders must be considered in the differential diagnosis of any patient with chronic, nonspecific complaints localized to the upper airway. An aggressive diagnostic and therapeutic approach may significantly decrease morbidity and death resulting from these lesions.