DIAGNOSIS IN ONCOLOGY

Lethal Midline Granuloma Revisited: Nasal T/NaturalKiller Cell Lymphoma

Arthur Skarin, MD, Consultant Editor
C. S. Chim, G. C. Ooi, T. W.H. Shek, R. Liang, Y. L. Kwong
Queen Mary Hospital, University of Hong Kong, Hong Kong

A 43-year-old man presented with a 3-month history of recurrent fever, nasal obstruction,
blood-stained nasal discharge, and weight loss of 8 kg. Physical examination revealed
erythema and swelling of midline facial features (Fig 1A) and bilateral submandibular
lymphadenopathy. Nasal endoscopy showed a 2.5-cm ulcer in the middle of the anterior
palate with foul-smelling discharge (Fig 1B). Repeated superficial biopsies of the ulcer
showed necrotic tissue only without infective organisms or neoplasia. An open biopsy
revealed an ulcerated (Fig 2A, arrow) palatal specimen with infiltration by a mixture of
small-, medium-, and large-size lymphoid cells, along with tissue necrosis (Fig 2A and
2B). Immunohistochemical study showed that these abnormal lymphoid cells were CD2+,
CD3 (Leu 4)-, CD3 +, CD4-, CD5-, CD15-, CD56+, and CD79a-. The diagnosis of naturalkiller (NK) cell lymphoma was established. A bilateral bone marrow biopsy did not reveal
evidence of lymphoma infiltration. In situ hybridization for Epstein-Barr-encoded RNA
showed nuclear staining in most of the medium- to large-size lymphoid cells (Fig 2C). A
complete blood picture showed a hemoglobin level of 11.4 g/L, platelet count of 287 x
109/L, and leukocyte count of 4.8 x 109/L with normal differential count. Blood urea,
creatinine, bilirubin, and transaminase levels were within normal limits. The lactate
dehydrogenase level was 1006 U/L (normal range, 200 to 400 U/L). The albumin level
was 26 g/L (normal range, 42 to 54 g/L). Axial (Fig 3A) T1-weighted gadoliniumenhanced magnetic resonance scans of the sinuses showed an enhancing soft tissue mass
destroying the nasal septum and medial wall of the left maxillary sinus, and polypoidenhancing lesions in both maxillary antra (arrow A). There was abnormal infiltration of
the subcutaneous tissues of the nose, cheeks, and upper lip (arrow B, Fig 3A and 3B).
There was also involvement of the right superior alveolar ridge (arrow A, Fig 3B) and
adjacent hard palate (arrow, coronal view, Fig 3C), with total erosion of the anterior hard
palate. An abdominal computed tomography scan revealed no intra-abdominal
lymphadenopathy or organomegaly. Treatment with cyclophosphamide, doxorubicin,
vincristine, and prednisone chemotherapy as well as local irradiation was initiated.

Fig 1.

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Fig 3.

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Clinically, our patient was diagnosed as having aggressive CD56+ nasal NK cell
lymphoma (angiocentric lymphoma in the Revised European-American Lymphoma
classification1) with extensive tissue necrosis.2-5 In the past, this entity has been referred to
by various names, such as polymorphic reticulosis, lethal midline granuloma, and midline
malignant reticulosis, which describe a group of destructive and clinically malignant
lesions involving the midline facial structures.3
Despite the malignant clinical course, histologic diagnosis can be difficult because of
extensive tissue necrosis, and often multiple biopsies may be required. The CD56+
lymphoma cells exhibit a broad morphologic spectrum with frequent angiocentricity,
angioinvasion, and zonal tumor necrosis. The nasal CD56+ NK lymphoma has a
characteristic immunophenotypic profile, ie, CD2+, surface CD3 (Leu4)-, cytoplasmic
CD3 +, cytoplasmic CD56+, and negative for other T-cell markers.2-5 The T-cell receptor
genes are characteristically in germline configuration. Interestingly, the clonal EpsteinBarr viral genome is present in almost all cases.5,6 Although most NK cell lymphomas
present in the nasal or upper aerodigestive tract, they may also involve other extranodal
sites (such as skin, testis, soft tissue, and gastrointestinal tract) and may rarely present
with a leukemic picture.2-4 In addition, although most cases of nasal lymphoma belong to

the NK cell category, true nasal T-cell lymphomas with rearranged T-cell receptor genes
have also been described.2,3
CD56+ NK cell lymphoma (both the nasal and the nonnasal type) is an aggressive disease.
Despite intensive combination chemotherapy, patients with localized disease have a
median disease-free and overall survival time of only 9 and 12 months, respectively, and
virtually none of the patients with disseminated disease survive beyond a few years.2-4,7
Recently, high-dose chemotherapy with autologous stem-cell rescue has been shown to be
beneficial in patients with nasal NK cell lymphoma.8
Quick Find

Rhinoscleroma
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Last Updated: August 15,
2002

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Synonyms and related keywords:

respiratory scleroma, scleroma, Mikulich
disease, rhinosclerosis, Klebsiella
rhinoscleromatis, K rhinoscleromatis,
scleroma respiratorium, nasal polyposis,
scleroma respiratorium

AUTHOR
INFORMATION

Section 1 of
9

Author Information Introduction Clinical Differentials

Workup Treatment Medication Follow-up Bibliography

Author: Egle Goriniene, MD, Staff

Physician, Department of Infectious
Diseases, New Jersey Medical
School
Coauthor(s): Robert A Schwartz, MD,
MPH, Professor and Head,
Dermatology, Professor of Pathology,
Pediatrics, Medicine, and Preventive
Medicine and Community Health,
UMDNJ-New Jersey Medical School
Editor(s): Jacek C Szepietowski,
MD, PhD, Professor and ViceHead, Department of Dermatology,
Venereology and Allergology,

Author Information
Introduction
Clinical
Differentials
Workup
Treatment
Medication
Follow-up
Bibliography

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Related Articles

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Basal Cell
Carcinoma
Leishmaniasis
Leprosy
Nasopalatine Duct
Cyst
Sarcoidosis
Sporotrichosis
Syphilis
Verrucous
Carcinoma
Wegener

University of Medicine at Wroclaw,

Poland; David F Butler, MD,
Professor, Texas A&M University
College of Medicine; Director,
Division of Dermatology, Scott and
White Clinic; Jeffrey P Callen, MD,
Chief, Professor, Department of
Internal Medicine, Division of
Dermatology, University of Louisville
School of Medicine; Glen H
Crawford, MD, Assistant Clinical
Professor, Department of
Dermatology, University of
Pennsylvania School of Medicine;
Chief, Division of Dermatology, The
Pennsylvania Hospital; and Dirk M
Elston, MD, Teaching Faculty,
Department of Dermatology,
Geisinger Medical Center
Disclosure

Section 2 of

INTRODUCTION

Author Information Introduction Clinical Differentials

Workup Treatment Medication Follow-up Bibliography

Background: Rhinoscleroma is a chronic

granulomatous condition of the nose and
other structures of the upper respiratory
tract. Rhinoscleroma is a result of
infection by the bacterium Klebsiella
rhinoscleromatis. After the polish surgeon
Johann von Mikulich described the
histologic features in 1877, von Frisch
identified the organism in 1882. In 1932,
Belinov proposed the use of the term
scleroma respiratorium because the
pathologic process in rhinosclerosis may

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involve not only the upper airways but

also the lower airways. In 1961, Steffen
and Smith demonstrated that K
rhinoscleromatis conformed to Koch's
postulates and that it was an etiologic
factor in the inflammatory changes typical
of scleroma.
Pathophysiology: Rhinoscleroma is
contracted by means of the direct
inhalation of droplets or contaminated
material. The disease probably begins in
areas of epithelial transition such as the
vestibule of the nose, the subglottic area
of the larynx, or the area between the
nasopharynx and oropharynx. Cellular
immunity is impaired in patients with
rhinoscleroma; however, their humoral
immunity is preserved.
The CD4/CD8 cell ratio in the lesion is
altered with decreased levels of CD4
lymphocytes; this change possibly
induces a diminished T-cell response.
Macrophages are not fully activated.
Mucopolysaccharides in the bacterial
capsule probably contribute to the
inhibition of phagocytosis. Otherwise,
patients are immunocompetent in every
regard except for the ineffective
phagocytosis of the organism by the
Mikulicz cells.
Rhinoscleroma usually affects the nasal
cavity, but lesions associated with
rhinoscleroma may also affect the larynx;
nasopharynx; oral cavity; paranasal
sinuses; or soft tissues of the lips, nose,
trachea, and bronchi.
Frequency:

In the US: The incidence of

rhinoscleroma appears to be
increasing in the United States.

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Rare sporadic cases occur in

the United States, usually in
immigrant populations arriving
from the countries in which the
disease is endemic.

Internationally:
Rhinoscleroma is considered
endemic in Central America,
Egypt, tropical Africa, India,
and Indonesia. Worldwide, 5%
of all cases occur in Africa.

Mortality/Morbidity:

Rhinoscleroma is rarely lethal,

unless it causes airway
obstruction.

The diagnosis may elude the

clinician for years, and this
delay can substantially
increase the rate or severity of
resultant morbidity.

Race: Patients of all races can be

affected.
Sex: Rhinoscleroma tends to affect
females somewhat more often than it does
males.
Age: Typically, rhinoscleroma appears in
patients aged 10-30 years.

CLINICAL

Section 3 of 9

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History: Rhinoscleroma should be

considered in patients from countries in

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which the disease is endemic if they have

nasal polyps that significantly adher to the
nasal septum with relative sparing of the
sinuses.
Most often, the presentation is
nonspecific.
Patients may present with the following:

Nasal obstruction (most

common complaint)

Rhinorrhea

Epistaxis

Dysphagia

Nasal deformity

Anesthesia of the soft palate

Difficulty breathing that

progresses to stridor

Dysphonia

Anosmia

Physical: The disease commonly affects

the nasal cavity (95-100% of patients),
but it can also affect the nasopharynx (1843%), larynx (15-40%), trachea (12%),
and bronchi (2-7%). The oral cavity,
paranasal sinuses, and soft tissues of the
lips and nose can be affected as well. In
rare cases, rhinoscleroma spreads to the
orbit.
Most often, the presentation is
nonspecific.
Rhinoscleroma is divided into 3 stages:
(1) the catarrhal, or atrophic, stage; (2) the

granulomatous stage; and (3) the sclerotic

stage.

Catarrhal, or atrophic, stage

o

This first stage begins

with a nonspecific
rhinitis that evolves into
purulent fetid rhinorrhea
and crusting.

This stage can last for

weeks or months.

Granulomatous, or
hypertrophic, stage
o

The nasal mucosa

becomes bluish red and
granular, with the
formation of rubbery
nodules or polyps in the
nose.

Epistaxis occurs with

nasal enlargement,
deformity, and
destruction of the nasal
cartilage (Hebra nose).

The damage may

progress to anosmia,
anesthesia of the soft
palate, enlargement of
the uvula, dysphonia,
and various degrees of
airway obstruction.

Lesions occur in the

form of atrophic
changes and
granulomas, and in the
fibrotic, thick, healed
stage.

The anterior-inferior part

of the antrum and its
medial wall are more
commonly affected than
other structures.

Involvement of the
maxillary antrum is
suggested in scleroma,
and the maxillary antrum
may act as a reservoir of
infection.

The soft palate is

markedly thickened at
its attachment to the
hard palate, which
tapers off toward its free
edge. This sign can help
in the early diagnosis of
the condition.

Physical examination
frequently reveals
erythematous granular
or nodular swellings
covered with crusts.

The tumorlike
appearance and local
spread are suggestive of
malignancy.

Sclerotic stage
o

The sclerotic stage is

characterized by
sclerosis and fibrosis.

The sclerotic stage

develops where the
nodules are replaced by
fibrous tissue leading to
extensive scarring and
possible stenosis.

Causes:

Rhinoscleroma is caused by
the gram-negative
coccobacillus K
rhinoscleromatis.

Although crowded conditions,

poor hygiene, and poor
nutrition appear to be
necessary for transmission of
the infectious agent, the actual
pathogenesis of infection
remains elusive.
Section 4 of

DIFFERENTIALS

Author Information Introduction Clinical Differentials

Workup Treatment Medication Follow-up Bibliography

Actinomycosis
Basal Cell Carcinoma
Leishmaniasis
Leprosy
Nasopalatine Duct Cyst
Sarcoidosis
Sporotrichosis
Syphilis
Verrucous Carcinoma
Wegener Granulomatosis
Other Problems to be Considered:
Vasculitis
Neoplastic disease (eg, lymphoma)
Extranodal Rosai-Dorfman disease
Infectious granulomatous processes may
include those caused by bacteria
(tuberculosis, actinomycosis, syphilis,
leprosy), fungi (histoplasmosis,
blastomycosis, paracoccidioidomycosis,
sporotrichosis), and parasites

(mucocutaneous leishmaniasis).
Rhinoscleroma can mimic various
inflammatory and neoplastic processes,
including leprosy,
paracoccidioidomycosis, sarcoidosis,
basal cell carcinoma, and Wegener
granulomatosis. Rhinoscleroma should be
added to the list of opportunistic
infections that can occur in patients
infected with the human
immunodeficiency virus.
Granulomatous lesions of the craniofacial
area are common. These lesions vary in
nature. They can be lymphohistiocytic
with or without eosinophils; they can be
tuberculoid with epithelioid cells and
giant cells; or, occasionally, they are
composed of essentially giant cells. The
etiology of these lesions may be known or
easy to find; their causes include foreign
body granulomas, sarcoidosis, leprosy,
rhinoscleroma, fungal diseases (especially
zygomycosis and rhinosporidiosis), and
parasitic diseases.
Lethal midline granuloma is a clinical
entity characterized by a necrotic and
relentlessly progressive destructive
presentation. After a malignant process
(especially lymphoid) and Wegener
granulomatosis are eliminated from the
differentials, the diagnosis is idiopathic
midline nonhealing granuloma. Some
lesions remain in the facial area, whereas
others disseminate as a malignant disease.
Central giant cell granuloma and
histiocytosis X (especially eosinophilic
granuloma) are 2 other varieties of
granuloma that differ from the
aforementioned granulomatous infiltrates
in their clinical presentation and
evolution.

WORKUP

Sectio

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Lab Studies:

Laboratory markers
o

A positive result with culturing in MacConkey agar is diagnostic of rhinoscleroma.

However, culture results are positive in only 50-60% of patients.

Bacterial identification
o

Bacteria can be seen by using periodic acid-Schiff, Giemsa, Gram, and silver stains.

A highly sensitive and specific method for identifying K rhinoscleromatis organisms is t

specimen with the immunoperoxidase technique.

Imaging Studies:

CT findings in primary nasal and nasopharyngeal rhinoscleroma include soft-tissue masses o

o

The lesions are characteristically homogeneous and nonenhancing, and they have dist

Adjacent fascial planes are not invaded.

The subglottic area is involved in laryngeal and tracheal scleroma.

The lesions primarily cause concentric irregular narrowing of the airway.

In the trachea, cryptlike irregularities are diagnostic of scleroma.

MRI should be performed in patients with rhinoscleroma.

o

Nasal masses can obstruct the ostiomeatal units, and secretions may be retained in th

In the hypertrophic stage of rhinoscleroma, both T1- and T2-weighted images show ch
marked high signal intensity.

Procedures:

Diagnosis is facilitated by the use of cytologic methods that are easy to perform and do not ca
(see Further Outpatient Care).

Cytologic analysis is performed on brushing specimens of a lesion.

The characteristic cells of the Mikulicz type may be observed in the smear.

This chronic infectious disease of the upper respiratory tract is routinely diagnosed by means
lesions.

Nasal endoscopy reveals signs of all 3 stages of scleroma: catarrhal, granulomatous, and scle

Bronchoscopy has a role in the early diagnosis of rhinoscleroma.

Histologic Findings: Histopathologic analysis has a definite role in the diagnosis of rhinoscleroma.
findings include large vacuolated Mikulicz cells and transformed plasma cells with Russell bodies. Th
macrophage with clear cytoplasm that contains the bacilli; this cell is specific to the lesions in rhinosc
most commonly diagnosed during the proliferative phase, in which the clinical and histologic present
recognized.

The histologic findings correspond to the 3 clinical stages. In the catarrhal (or atrophic) stage, squamous metap
subepithelial infiltrate of polymorphonuclear leukocytes with granulation tissue are observed. In the granulom
features include chronic inflammatory cells, Russell bodies, pseudoepitheliomatous hyperplasia, and groups of
that contain K rhinoscleromatis organisms (Mikulicz cells). If numerous, these bacteria can be seen with hema
but periodic acid-Schiff, silver impregnation, or immunohistochemical staining may be required to confirm the
the sclerotic stage, extensive fibrosis may lead to stenosis and disfiguration.

Microscopically, the connective tissue is highly vascular, with an inflammatory infiltrate consisting primarily o
lymphocytes and a possible sprinkling of eosinophils. Russell bodies in the plasma cells are common. Howeve
sheets of large (100- to 200-mm) vacuolated histiocytes (ie, Mikulicz cells) that contain the causative agent are
organisms are occasionally visible on standard hematoxylin and eosin stains, they are more readily demonstrat
impregnation Warthin-Starry stains. The exudative stage results in a dense nonspecific fibrosis. In the exudativ
Mikulicz cells may be difficult to detect.

Electron microscopy reveals large phagosomes filled with bacilli and surrounded by a finely granular or fibrill
in a radial pattern. This finding represents the accumulation of antibodies on the bacterial surface (type A gran
aggregation of bacterial mucopolysaccharides surrounded by antibodies (type B granules).
TREATMENT

Sectio

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Medical Care: Bronchoscopy has a role in the initial treatment of symptoms. Treatment should also include lo
therapy and surgical intervention in patients with symptoms of obstruction.

Bacterial overinfection responds to treatment with third-generation cephalosporins and clindam

Sclerotic lesions respond well to treatment with ciprofloxacin.

Surgical Care: Surgery combined with antibiotic therapy is beneficial in patients with granulomatous disease
obstruction or nasal sinus involvement due to the proliferation of lesions.

Tracheotomy should be considered in patients with laryngeal obstruction of the second degre
and above (sclerotic stage).

Plastic surgery is necessary in patients with cicatricial stenosis or when imperforation remains
pharynx, larynx, or trachea (Sun, 1998).

Extensive granulomatous lesions are treated by means of open excision by using the laryngo
the best method for a quick recovery in patients without evidence of subglottic stenosis.

Surgery and laser therapy are required to treat airway compromise and tissue deformity. Fibe
assessment of the pathology and subsequent passage of a cuffed tracheal tube to secure the
respiratory obstruction as the fiberscope passes through the opening in the membrane, either
technique of preoxygenation and voluntary hyperventilation followed by breath holding during
The thin caliber and maneuverability of the flexible fiberoptic bronchoscope makes fiberoptic i
technique for airway management in cicatricial membranes of the pharynx.

Treatment of the advanced cicatrix with carbon dioxide laser vaporization yields excellent resu

Obstructive lesions of the larynx and subglottic space are always a challenging problem
anesthetist. At this level of the obstruction, the effectiveness and innocuous nature of c
treatment are related to the degree of endoscopic exposure. Because of the transtrach
ventilator, ensuring a free laryngeal endoscopic operative field is now possible. The tra
introduced percutaneously through the cricothyroid membrane into the trachea under e
connected to a high-frequency jet ventilator.

Among many advantages of this technique, the most convincing include a clear operat
complete relaxation of the patient, good respiratory gas exchange, elimination of the ris
endotracheal tube with the laser, decrease in the risk of aspiration of blood and debris,
oxygen and/or mechanical ventilation in the postoperative period.

Palatal symptoms may be relieved by means of uvulopalatopharyngoplasty.

Consultations:

Consultation with a plastic surgeon may be helpful in patients with cicatricial stenosis or in tho
the nasal cavity, pharynx, larynx, or trachea.

An endoscopist and an anesthetist may be required to perform vaporization with a carbon dio

MEDICATION

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The goals of pharmacotherapy are to eradicate the infection, reduce morbidity, and prevent complications.

Drug Category: Antibiotic agents -- Tetracycline is the drug of choice. Other antibiotics include ciprofloxa

overinfection responds to treatment with clindamycin and third-generation cephalosporins. Sclerotic lesions re
ciprofloxacin. Ciprofloxacin has the following advantages: Its oral administration is convenient, it achieves go
concentrated in macrophages, and it may prove useful in the treatment of patients with rhinoscleroma.

Drug Name

Ciprofloxacin (Cipro) -- Fluoroquinolone with activity against

Pseudomonas species, streptococci, MRSA, Staphylococcus
epidermidis, and most gram-negative organisms but no activity
against anaerobes. Inhibits bacterial DNA synthesis and,
consequently, growth. Continue treatment for at least 2 d (7-14 d
typical) after signs and symptoms have disappeared.

Adult Dose

250-500 mg PO bid for 7-14 d

Pediatric Dose
Contraindications
Interactions

<18 years: Not recommended

>18 years: Administer as in adults
Documented hypersensitivity
Antacids, iron salts, and zinc salts may reduce serum levels;

administer antacids 2-4 h before or after fluoroquinolone dose;

cimetidine may interfere with metabolism of fluoroquinolones;
reduces therapeutic effects of phenytoin; probenecid may
increase serum concentrations; may increase toxicity of
theophylline, caffeine, cyclosporine, and digoxin (monitor
digoxin levels); may increase effects of anticoagulants (monitor
PT)
Pregnancy

C - Safety for use during pregnancy has not been established.

Precautions

In prolonged therapy, periodically evaluate organ system (eg,

renal, hepatic, hematopoietic) function; adjust dose in renal
function impairment; superinfections may occur with prolonged
or repeated antibiotic therapy

Drug Name

Cefixime (Suprax) -- Third-generation cephalosporin. Arrests

bacterial cell wall synthesis and inhibits bacterial growth by
binding to one or more penicillin-binding proteins.

Adult Dose

200 mg PO q12h or 400 mg/d PO qd or divided q12h

Pediatric Dose

<12 years: 8 mg/kg/d susp PO qd or 4 mg/kg PO bid

>50 kg or >12 years: Administer as in adults

Contraindications

Documented hypersensitivity

Interactions

Coadministration with aminoglycosides increases nephrotoxicity;

probenecid may increase effects

Pregnancy

B - Usually safe but benefits must outweigh the risks.

Precautions

Adjust dose in severe renal insufficiency (high doses may cause

CNS toxicity); prolonged or repeated use may cause
superinfections and promote growth of nonsusceptible
organisms

Drug Name

Rifampin (Rifadin, Rimactane) -- Inhibits DNA-dependent

bacteria by binding to beta subunit of DNA-dependent RNA
polymerase, blocking RNA transcription.

Adult Dose

600 mg/d PO/IV single daily dose

Pediatric Dose
Contraindications
Interactions

10-20 mg/kg PO/IV; not to exceed 600 mg/d

Documented hypersensitivity
Induces microsomal enzymes, which may decrease effects of
acetaminophen, oral anticoagulants, barbiturates,
benzodiazepines, beta-blockers, chloramphenicol, oral
contraceptives, corticosteroids, mexiletine, cyclosporine,
digitoxin, disopyramide, estrogens, hydantoins, methadone,
clofibrate, quinidine, dapsone, tazobactam, sulfonylureas,
theophyllines, tocainide, and digoxin; coadministration with
enalapril may increase BP; coadministration with isoniazid may
increase rate of hepatotoxicity more than with either agent alone

(discontinue 1 or both if LFT results change)

Pregnancy

C - Safety for use during pregnancy has not been established.

Precautions

Obtain CBCs and baseline clinical chemical values prior to and

throughout therapy; in liver disease, weigh benefits against risk
of further liver damage; interruption of therapy and high-dose
intermittent therapy associated with thrombocytopenia
(reversible if therapy discontinued as soon as purpura appears);
if treatment continued or resumed after purpura appears,
cerebral hemorrhage or death may occur

Drug Name

Clindamycin (Cleocin) -- Lincosamide for treatment of serious

skin and soft tissue staphylococcal infections. Also effective
against aerobic and anaerobic streptococci (except
enterococci). Inhibits bacterial growth, possibly by blocking
dissociation of peptidyl tRNA from ribosomes and causing arrest
of RNA-dependent protein synthesis.

Adult Dose

150-450 mg/dose PO q6-8h; not to exceed 1.8 g/d

600-1200 mg/d IV/IM divided q6-8h depending on degree of
infection

Pediatric Dose
Contraindications

8-20 mg/kg/d (hydrochloride) PO divided tid/qid

8-25 mg/kg/d (palmitate) PO divided tid/qid
20-40 mg/kg/d (phosphate) IV/IM divided tid/qid
Documented hypersensitivity; regional enteritis; ulcerative
colitis; hepatic impairment; antibiotic-associated colitis

Interactions

Increases duration of neuromuscular blockade induced by

tubocurarine and pancuronium; erythromycin may antagonize
effects; antidiarrheals may delay absorption

Pregnancy

B - Usually safe but benefits must outweigh the risks.

Precautions

Adjust dose in severe hepatic dysfunction; no adjustment

necessary in renal insufficiency; associated with severe and
possibly fatal colitis by allowing overgrowth of Clostridium
difficile

Drug Category: Corticosteroid agents -- These agents have anti-inflammatory properties and cause profou
effects. Corticosteroids modify the body's immune response to diverse stimuli.

Drug Name

Prednisone (Deltasone, Meticorten, Orasone) -- May decrease

inflammation by reversing increased capillary permeability and
suppressing PMN activity.

Adult Dose

5-60 mg/d PO qd or divided bid/qid; taper over 2 wk as

symptoms resolve

Pediatric Dose

4-5 mg/m2/d PO; alternatively, 0.05-2 mg/kg PO divided bid/qid;

taper over 2 wk as symptoms resolve

Contraindications

Documented hypersensitivity; viral, fungal, connective tissue, or

tubercular skin infections; peptic ulcer disease; hepatic
dysfunction; GI tract disease

Interactions

Coadministration with estrogens may decrease clearance;

concurrent digoxin may cause digitalis toxicity secondary to
hypokalemia; phenobarbital, phenytoin, and rifampin may
increase metabolism of glucocorticoids (consider increasing
maintenance dose); monitor for hypokalemia with
coadministration of diuretics

Pregnancy

B - Usually safe but benefits must outweigh the risks.

Precautions

Abrupt discontinuation of glucocorticoids may cause adrenal

crisis; hyperglycemia, edema, osteonecrosis, myopathy, peptic
ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis,
myasthenia gravis, growth suppression, and infections may
occur with glucocorticoid use

FOLLOW-UP

Sectio

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Further Inpatient Care:

Bronchoscopy plays a role in the follow-up care of patients.

Further Outpatient Care:

Owing to the high rate of recurrence, prolonged antibiotic therapy (months to years) is necess

Nasal cytology is an easy and noninvasive investigation.

This method can be performed on an outpatient basis as an adjuvant to clinical and his
along with nasal endoscopy.

Nasal cytology is a simple, reliable, and timesaving procedure that can be used with fu

Relapses occur, and close observation is the key to the long-term follow-up care of the patien

In/Out Patient Meds:

The choice of long-term antibiotic therapy should be guided by the patient's age and sex.

Repeat biopsy can be performed to help determine the appropriate duration of the antibiotic th

Complications:

Rhinoscleroma is a rare cause of upper airway obstruction. Only isolated studies in the literatu
tracheal obstruction.

Scleroma is known to cause slowly progressive asphyxia.

Prognosis:

The course is usually chronic.

Relapses can occur.

Lethal midline granuloma in Okinawa with special emphasis on polymorphic

reticulosis.
Jpn J Cancer Res. 1994 Apr;85(4):384-8. Unique Identifier : AIDSLINE MED/94259652

Kojya S; Itokazu T; Maeshiro N; Esu H; Noda Y; Mishima K;

Ohsawa M; Aozasa K; Department of Otorhinolaryngology,
University of the Ryukyus; Faculty of Medicine, Okinawa.
Abstract: Lethal midline granuloma (LMG) is a clinical term used to describe a condition which may be
manifested histologically as Wegener's granulomatosis (WG), polymorphic reticulosis (PR), and malignant
lymphoma (ML). WG is an inflammatory disease, and PR and ML are considered to represent a
neoplastic proliferation of lymphoreticular cells. In this report, twenty-two cases of LMG in Okinawa were
examined. The frequency of LMG per 100,000 outpatients of the ear, nose and throat clinic in Okinawa was
67, and the higher frequency of PR (27) and ML (34) in Okinawa than in other districts of Japan was
characteristic. Polymerase chain reaction, in situ hybridization, and immunohistochemical studies showed
that the proliferating cells in PR were CD43+ and simultaneously contained Epstein-Barr viral genome in
their nuclei. The higher frequency of PR and ML in Okinawa is discussed in conjunction with a review of
pertinent literature: multiple factors including genetic, viral environmental, and socioeconomic factors seem
to affect the frequencies of these diseases.

Lethal midline granuloma

progressively destructive condition of uncertain aetiology, involving the nose and
paranasal sinuses. It leads to erosion of the sinonasal and adjacent structures, when left
untreated eventually causing death by extension to the central nervous system, infection
or haemorrhage.
Radiologically, midfacial bone destruction with relatively little associated soft tissue
thickening is seen. This condition resembles the findings in Wegeners granulomatosis
head and neck manifestation, although in the latter the changes are less pronounced

Wegener's granulomatosis, head and neck

manifestation

(Friedrich Wegener, 20th century, German pathologist), systemic disease primarily

affecting the upper respiratory tract, lungs and kidneys. It is characterized by necrotizing
granuloma, vasculitis and glomerulonephritis. Patients usually present with constitutional
symptoms such as fever and weight loss. They may also have nasal discharge and
sinusitis; clinical examination reveals a crusted, granular mucosa, with ulceration and
bone destruction. CT shows bone destruction in the nose and paranasal sinuses, without
a significant soft tissue mass (Fig. 1). Similar, but more pronounced, abnormalities are
seen in lethal midline granuloma .
In about 20% of cases, Wegener's granulomatosis also involves the orbit. Wegener's
granulomatosis limited to the orbits is very rare. The orbital symptoms are the same as
those of orbital pseudotumour but patients with Wegener's granulomatosis usually have
constitutional symptoms. Wegener's granulomatosis may affect the larynx; soft tissue
thickening causing subglottic or glottic stenosis is seen in such cases (Fig. 2). Soft tissue
masses mimicking a malignant tumour of the nasopharynx or skull base have also been
described.
A positive titre for c-ANCA is a diagnostic criterion for Wegener's granulomatosis. This
cytoplasmic antibody directed at neutrophil cytoplasmic antigen is elevated during
periods of active disease. In the absence of respiratory tract or renal lesions, the
diagnosis cannot be confirmed until the elevated c-ANCA titers are identified. For a
general description of the disease, see Wegener's granulomatosis .
RH

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Fig. 1a
Axial CT image of nose. Septal perforations and defect in left inferior turbinate
(arrowheads), without associated soft tissue thickening.

Wegener's
granulomatosis, head
and neck manifestation,
Fig. 1a

Wegener's
granulomatosis, head
and neck manifestation,
Fig. 2a

Lethal Midline Granuloma: Report of Three Cases

Shin-Yu Lu, DDS; Wei-Jen Chen1, MD; Hock-Liew Eng1, MD

Lethal midline granuloma (LMG) is a rare clinical entity characterized by progressive

relentless ulcerations and necrosis of midfacial structures. It occurs more frequently in
Oriental than in Western populations with no demonstrable etiology. Treatment and
outcome for cases differ, but their pathological distinction may not always be possible
from routine biopsy specimens. The histological features often seen include widespread
coagulative necrosis, heavy inflammatory infiltrates, and atypical pleomorphic cells.
However, the paucity of these atypical cells in biopsy specimens and the degree of
necrosis can make the diagnosis of a neoplastic lesion very difficult. Because of the
progress in pathology methodology including immunohistochemistry, most cases have
been proven to be malignant lymphomas of T-cell lineage.
We present 3 patients for whom an initial clinical diagnosis of LMG was made. From
their several oral biopsies and nasal specimens, difficulties were encountered in
differentiating "midline granuloma" from other possible diseases using
histomorphological criteria alone. After extensive evaluations, malignant T-cell
lymphoma was the specific disease entity identified in only one case by cell membrane
immunostaining technique. A literature review was carried out, and recent concepts of the
etiology and pathogenesis of this disease are presented.
(Chang Gung Med J 2000;23:99-106)

Key words: lethal midline granuloma, T-cell lymphoma.