Midline Destructive Lesions of Face: A Dermatology Perspective
Year: 2025
Type: article
Abstract: Introduction Midline destructive lesions (MDLs) of the face were first described in 1897, which include various conditions causing progressive midfacial destruction. Various terminologies have been used for MDL, like idiopathic midline granuloma, idiopathic midline destructive disease, lethal midline granuloma, malignant granuloma, midline nonhealing granuloma, midline malignant reticulosis, midline granuloma syndrome, midfacial granuloma syndrome, lymphomatoid reticulosis nonhealing midline granuloma, polymorphic reticulosis, granuloma gangrenosum, and Stewart syndrome.[1] It is defined as destruction or relentless erosion of the midline structures of the face, particularly nasal cavity (nasal skin/cartilage/bone), palate, and surrounding tissue. Etiology includes infections (varying geographically), autoimmune disorders, malignancies, vascular conditions, idiopathic, and trauma [Table 1]. Common symptoms include nasal congestion, mucopurulent secretions, epistaxis, voice changes, sinusitis, septal perforation, pain, and bony erosions.[1-3] Diagnosis is often challenging, and a multidisciplinary approach may be required. Cutaneous manifestations play a critical diagnostic clue aiding in early diagnosis. This review explores the causes of MDL, emphasizing dermatological insights for accurate and early diagnosis.Table 1: List of etiological causes in dermatology causing centro-facial destruction of lesionsInfective Disorders Leprosy: Leprosy is a chronic infectious disease caused by Mycobacterium leprae, primarily affecting the skin and peripheral nerves. Although less common, involvement of mucosal surfaces and internal organs has also been documented. Despite global efforts, leprosy remains a public health concern in several regions, with over 80% of cases reported from seven countries—India, Brazil, Indonesia, Madagascar, Myanmar, Nepal, and Nigeria. MDLs are common in the lepromatous pole, with the nasal cavity as the first site of bacillary inoculation.[4] Pathology begins with mucosal edema and granulomatous infiltration, progressing to involve the anterior-inferior turbinate, anterior septum (Kiesselbach area), nasal cartilage, maxillary sinus, and oral structures (palate, uvula, tonsils, pharynx, and larynx). Clinical features include chronic rhinitis, nasal obstruction, hyposmia/anosmia, epistaxis, and progressive nasal cartilage destruction (saddle nose deformity). Palate perforation and muffled/hoarse voice can occur and may worsen during type 2 lepra reactions.[3,4] A classic triad of saddle nose, septal perforation, and atrophic rhinitis are seen in the advanced stage. A diagnosis of leprosy is confirmed clinically by skin/ear infiltration, peripheral nerve thickening with sensory loss, and demonstration of acid-fast bacilli on slit-skin smear examination and histopathology.[4] Tuberculosis: Lupus vulgaris presents as soft reddish-brown papule/plaque/nodule (apple jelly nodules appearance on diascopy), which grows peripherally with central scarring and may ulcerate. It predominantly involves the nasal cartilage (spares nasal bone) and may extend to involve the gingiva, palate, pharynx, and larynx via lymphatic spread, leading to deformities.[5] Orofacial tuberculosis (TB) is an uncommon form of extrapulmonary TB, accounting for about 0.1% to 5% of all TB cases. Orofacial TB arising from contagious spread from lungs manifests as ulcers, gingivitis, periapical granuloma, and osteomyelitis involving the maxillary sinus and jaw.[6] Posterior nasal nares involvement is rare, and nasal floor is almost spared. It may spread to the ethmoid, frontal, sphenoid, maxillary sinus, and orbit. Definitive diagnosis is confirmed through histopathology, culture, acid-fast bacilli stain, Mantoux test and TB-Polymerase Chain Reaction (PCR)/Tissue Cartridge-Based Nucleic Acid Amplification Test (CBNAAT).[5,6] Sporotrichosis: Fixed cutaneous or disseminated form is associated with MDL. Endemic to several parts of Latin America and Asia, sporotrichosis is caused by dimorphic fungi of the Sporothrix genus. It is transmitted through local digital trauma, direct contact, and hematogenous and infected zoonotic sources. It mainly affects the anterior nasal septum and extends to the skin (muco-cutaneous). There is infiltration, crusting, granulation, microabscess formation, and rarely perforation/destruction of the anterior nasal septum [Figure 1] and maxillary sinus, as well as oropharyngeal involvement.[7] Diagnosis is confirmed through mycological culture, histopathological and molecular identification through PCR, and loop-mediated isothermal amplification.[7] Histoplasmosis: This is an invasive mycosis which is mostly acquired through the respiratory route. Mucocutaneous involvement is seen in 10–25% cases of disseminated histoplasmosis.[8] It has various manifestations like molluscum-like lesions, papules, keratotic plaques, pustules, acneiform eruptions, erosions, ulceration, and large fleshy growths.[8,9] Nasopharyngeal and maxillary involvement is a rare presentation. It oftem involves the palate, tongue, gingiva, and rarely the larynx.[10] It may lead to the destruction of nasal cartilage.[11] There is no significant lymphadenopathy. Definitive diagnosis is confirmed through mycological culture and histopathological and molecular identification through PCR.[9,10] Leishmaniasis: Leishmaniasis is a neglected tropical disease. Clinical presentation varies from erythematous papulonodular changes to scaly or ulcerative erythematous plaques with massive central hemorrhagic crust.[12] Mucocutaneous leishmaniasis results from lymphatic or hematogenous spread and is more common in the New World. Over 90% of cutaneous leishmaniasis cases worldwide are reported from a few endemic countries, including Afghanistan, Pakistan, Syria, Saudi Arabia, Algeria, and Iran.[12,13] It can mimic nasal inflammatory or malignant lesions, leading to ulceration and destruction of nasal cavities and the alae of nose and lips. Perforation of the nasal septum along with hypertrophy of the soft plate and uvula can be seen.[12,13] Diagnosis is confirmed by demonstration of amastigote on Giemsa stain or histopathology, serology (rk39), or molecular identification through PCR.[12,13] Rhinoscleroma: Rhinoscleroma is a chronic granulomatous inflammatory disease caused by Klebsiella rhinoscleromatis, affecting the nasal passages and upper respiratory tract. Rhinoscleroma is endemic in the Middle East, Central and South America, and Eastern Europe, though sporadic cases have been documented globally. The nose is involved in 95% to 100% of cases, making it the most commonly affected site. Clinically, it presents in three phases: catarrhal (rhinitic), granulomatous/nodular (intranasal nontender rubbery dusky red stony hard nodule, diffuse swelling of upper lip, gingiva, with crusting and fissured lip), and sclerotic (nasal deformity/retracted palate).[14] The palatal sign/V-shape deformity of soft palate is a diagnostic feature on radiography. Diagnosis is confirmed on histopathology showing abundant plasma cells with Russel bodies and Mikulicz cells and presence of Gram-negative/PAS-positive intracytoplasmic bacilli.[14] Syphilis: MDL is seen in lues maligna/malignant syphilis, gummatous syphilis, and congenital syphilis. Globally, syphilis affects an estimated 6 million individuals annually among people aged 15 to 49 years. Lues maligna presents as an ulcerative lesion with central necrosis, with overlying thick adherent crust. Gummatous syphilis presents as a granulomatous nodule (rubbery texture) with central necrosis, which ulcerates and leads to destruction of the nasal bone (saddle deformity), nasal septum, nasal alae, and hard and soft palate, followed by sclerosis.[11,15] Congenital syphilis can also lead to nasal cartilage destruction (saddle nose). Specific and nonspecific treponemal tests aid in confirmation of the diagnosis.[11,15] Mucormycosis: Mucormycosis is a serious fungal infection primarily caused by Mucorales species. It commonly affects individuals with compromised immunity—especially those with hematologic cancers, organ transplants, diabetes, or diabetic ketoacidosis—and can also occur in patients with severe traumatic wounds. The COVID-19 pandemic in India led to a surge in mucormycosis. Even before the COVID-19 pandemic, India was considered hyperendemic for mucormycosis, with an estimated disease burden nearly 70 times higher than the global average and over 200,000 cases recorded annually.[16] Clinically, it presents in various forms, with rhino-orbital-cerebral, pulmonary, and cutaneous types being most frequent. Clinical signs of mucormycosis may include greyish or reddish nasal mucosa, often accompanied by eschar formation on the nasal septum and palate, epistaxis, and palatal ulceration. Ocular involvement can manifest as conjunctival chemosis, proptosis, fixed pupil, nystagmus, ophthalmoplegia, and visual loss. Patients may also present with orbital cellulitis and erythema or swelling on the cheek. Histologically, it is characterized by broad, nonseptate or sparsely septate hyphae with irregular branching, typically at right angles. These fungal elements invade blood vessels, leading to thrombosis, tissue infarction, and necrosis. Extensive angioinvasion and perineural infiltrate are commonly observed, along with a mixed inflammatory response, including neutrophils and necrotic debris.[16] Figure 1: (a). A case of sporotrichosis presenting with widening of the right nostril and induration of the upper lip, nasal septa, columella, and abscess formation with overlying scaling. (b). Progression to ulceration with overlying crust formation over 2 weeks. (c) Complete resolution post-treatment with saturated solution of potassium iodide and Itraconazole and without recurrence at 1 year follow-upAutoimmune ANCA-associated vasculitis: Granulomatosis with polyangiitis (GPA) and eosinophilic granulomatosis with polyangiitis (EGPA) can cause midline facial destruction, along with affecting the kidneys, lungs, eyes, nervous system, and skin. ANCA-associated vasculitis (AAV) is an uncommon condition, affecting approximately 200 to 400 individuals per million. Granulomatosis with polyangiitis presents yellowish-brown nasal crust extending over the maxilla, which bleeds and ulcerates when removed, with surrounding periorbital and facial edema [Figure 2]. Other cutaneous features include papulonecrotic ulcers, nodules, petechiae/purpura, vasculitic ulcers, acneiform eruptions, livedo reticularis, blisters, gangrene, gingival hypertrophy, urticaria, and mucopurulent sinus discharge.[17] Nasal cartilage, bone, turbinates, sinuses, palate, and pharynx may be destroyed.[18] Systemic lupus erythematosus: Systemic lupus erythematosus (SLE) can cause nasal septal perforation and ulceration, often undiagnosed due to its asymptomatic nature.[19] It has a global incidence of approximately 5.14 per 100,000 person-years, with about 400,000 new cases diagnosed each year. The nasal mucosa appears diffusely erythematous and edematous, with crusting at the antero-inferior septal cartilage. Hypertrophied inferior turbinate and torus palatinus can occur. Ischemia, chondrolysis, and systemic vasculitis contribute to this condition.[19] IgG 4-related disease: IgG 4-related disease (IgG4-RD) is a fibro-inflammatory disease with the male to female ratio being 2:1. It initially presents as chronic rhinitis, blood-stained nasal discharge, and progressive nasal obstruction. Further progression can lead to destruction of the nasal septum, hard or soft palate, resulting in septal or palatal perforations and, in severe cases, complete loss of the uvula and development of a saddle-nose deformity due to collapse of the nasal bridge. Additional symptoms may include a chronic sore throat, difficulty in swallowing, especially with nasal regurgitation of fluids, and a nasalized speech pattern. A definitive diagnosis of IgG4-related disease relies on histopathological confirmation, as outlined by the International Consensus Criteria. These include a dense lymphoplasmacytic infiltrate, storiform-patterned fibrosis, and obliterative phlebitis. Additionally, there must be an elevated count of IgG4-positive plasma cells, with an IgG4 to total IgG plasma cell ratio exceeding 40%.[20] Pyoderma gangrenosum: Pyoderma gangrenosum (PG) is a noninfectious, inflammatory skin condition classified among neutrophilic dermatoses. Its estimated incidence is around 0.63 cases per 100,000 people, with a median age of onset of 59 years.[21] Clinical features may include ulcerations, septal abscesses, chronic sinusitis, saddle nose deformity, and nasal septal perforation. It is also frequently associated with systemic conditions such as inflammatory bowel diseases (e.g. Crohn’s disease and ulcerative colitis), rheumatoid arthritis, hematologic abnormalities, and liver disorders. Histopathological examination typically reveals a prominent neutrophilic infiltrate, often accompanied by neutrophilic pustules and areas of abscess formation.[21] Figure 2: (a). A case of Wegener’s granulomatosis showing facial and periorbital edema with erythema and swelling of the lower two-thirds of nose with hemorrhagic crust. (b). Destruction of nasal cartilage with granular appearing mucopurulent discharge and gross destruction endonasallyMalignancy Basal cell carcinoma (BCC): Nodular BCC commonly affects the nose, nasolabial folds, eyelids, cheeks, and forehead. It accounts for 80–90% of skin cancers. It presents as crusting, recurrent bleeding, and ulceration, with rolled-out borders (rodent ulcer), with potential nasal cartilage destruction [Figure 3] and overlying telangiectasia. Histopathology shows aggregates of basaloid cells with scanty cytoplasm and large hyperchromatic nuclei with peripheral palisading arrangement and peritumoral clefting in a fibromyxoid stroma. Squamous cell carcinoma (SCC): SCC arises from keratinized or mucosal epithelium. Globally, it accounts for approximately 890,000 new cases annually (about 4.5% of all cancer diagnoses) and 450,000 deaths (around 4.6% of global cancer mortality).[22] Predisposing factors include lichen sclerosus et atrophicus, verrucous discoid lupus erythematosus, lichen planus hypertrophicus, post-burn scar, renal transplant, and xeroderma pigmentosum. Sinonasal SCC is rare but aggressive, and presents as an ulcerative plaque with nodules and hemorrhagic crust.[23] It rapidly invades skin, nasal bone (saddle nose deformity), and palate and may extend intraocularly or intracranially.[23] Histopathology shows aggregates of pleomorphic squamous epithelial (keratin pearls) cells invading into the dermis. Extranodal natural killer/T-cell (NK/T-cell) – Nasal type lymphoma: A progressive ulcero-necrotic tumor affecting people 40–50 years of age, involving the nasal cavity, palate, and nasopharynx, and extending to the skin, sinuses, and orbit, causing significant midline facial destruction with necrotic whitish tissue [Figure 4] with pus discharge.[2,24] In Asia and South America, NK/T-cell lymphoma (NNKTL) accounts for 3–10% of non-Hodgkin lymphomas, compared to less than 1% in Western countries. Diagnosis is based on clinical features, B-symptoms, histopathology (atypical lymphoid cells with angiocentric and angiodestructive patterns), and immunohistochemistry (NK/T cell markers, EBV LMP, perforin, FAS-ligand, ICAM-1).[24] Figure 3: A case of basal cell carcinoma presenting as an atrophic plaque with rolled-out borders, central ulceration, and loss of nasal cartilageFigure 4: A case of nasal-type NK/T-cell lymphoma, showing destructive whitish necrotic ulceration with perilesional erythema and induration of the surrounding skinApart from the mentioned causes, other causes include burn [Figure 5], trauma, idiopathic, vascular tumor, renal disease, steroid abuse, toxin (cocaine), and cement exposure [Table 2].Figure 5: A case of burn injury presenting with scarring and loss of nasal cartilageTable 2: Summarizing other etiology of MDLs with specific clinical features and histopathologyTo conclude, MDL comprises a heterogeneous group of disorders that often require a multidisciplinary approach. However, by correlating the cutaneous manifestations with the underlying structures in the various causes of MDL, along with assessment of involvement of the systems and histopathological evaluation, dermatologists can often play a key role in the diagnosis. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form the patients have given their consent for their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest. Use of artificial intelligence (AI) We have not used artificial intelligence.
Authors: Bhairaw S. Agrawal, Suvesh Singh, Dharmendra Kumar, Saloni Tiwari
Institution: Narayan Medical College and Hospital
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W4416814163