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Year : 2018  |  Volume : 9  |  Issue : 4  |  Page : 191-196

Mucormycosis – Can the diagnosis be challenging at times??

Department of Oral Pathology, Narayana Dental College and Hospital, Nellore, Andhra Pradesh, India

Date of Web Publication18-Dec-2018

Correspondence Address:
Vandana Raghunath
Department of Oral Pathology, Narayana Dental College and Hospital, Chinthareddypalem, Nellore - 524 003, Andhra Pradesh
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/srmjrds.srmjrds_53_18

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Mucormycosis is an aggressive and often rapidly progressing fatal form of fungal infection mainly affecting the immunocompromised patients and characterized by destruction and necrosis. The paranasal sinuses get affected commonly in the rhinocerebral type with or without oral cavity involvement. At times, even in the setting of immunosuppression, it presents as a subtle clinical infection posing both as a diagnostic and therapeutic challenge to the clinicians. Further, in such immunocompromised cases, early diagnosis and prompt treatment become utmost demanding to prevent the ensuing morbidity and mortality. We present one such indolent case which presented as a sinus infection in a 50-year-old diabetic woman. Further, the granulomatous presentation on hematoxylin and eosin-stained sections led to an erroneous initial diagnosis, which later upon Grocott's methenamine silver staining was diagnosed as mucormycosis-rhinocerebral type. Thus, both clinical and histopathological presentations were defying.

Keywords: Diabetes mellitus, immunocompromised, mucormycosis, paranasal sinus, rhinocerebral

How to cite this article:
Raghunath V, Priyanka K H, Kiran C G, Deepthi R M. Mucormycosis – Can the diagnosis be challenging at times??. SRM J Res Dent Sci 2018;9:191-6

How to cite this URL:
Raghunath V, Priyanka K H, Kiran C G, Deepthi R M. Mucormycosis – Can the diagnosis be challenging at times??. SRM J Res Dent Sci [serial online] 2018 [cited 2023 May 28];9:191-6. Available from:

  Introduction Top

Mucormycosis is a rare, opportunistic, aggressive, fulminant, and frequently fatal infection, contributing to 8.3%–13.0% of all fungal infections. It is caused by a common inhabitant of the human upper airway, the Rhizopus, and other members of the order Mucorales, with the most important species being Rhizopus arrhizus (oryzae).[1],[2] Clinically, five major forms have been recognized which include the rhinocerebral (RCM) (44%–49%), which is the most common form, followed by cutaneous (10%–16%), pulmonary (10%–11%), disseminated (6%–11.6%), and gastrointestinal (2%–11%) forms.[3] The RCM form usually presents as a paranasal infection with or without an extension into the oral cavity, especially in the immunocompromised individuals and is rarely seen in the healthy or immunocompetent individuals.[4] Clinical infection usually progresses rapidly, causing death within few days of presentation. Microscopically, the tissue shows acute inflammatory changes and areas of necrosis.[5] However, on occasions, indolent presentations, even in the setting of immunosuppression, prove to cause considerable dilemma to the clinicians and also prove challenging to the histopathologists. Early diagnosis becomes mandatory as it can become life threatening owing to the invasive ability of the fungi into blood vessels, embolizing to distant organs, including the brain. This article reports a clinical case of an indolent form of paranasal mucormycosis infection in an elderly diabetic woman, which presented histologically as a granulomatous infection of the maxillary sinus, leading to an erroneous initial diagnosis.

  Case Report Top

A 50-year-old female patient reported to the outpatient department with a chief complaint of a diffuse, painless swelling on the left side of the face for 1 year. Detailed history revealed that the swelling was initially unnoticeable and had gradually developed. The patient was diabetic and was under medication for 12 years. She was also suffering with bouts of allergic rhinitis and cough for 20 years and was being treated if necessary si opus sit. Family history revealed that her demised father was a tuberculosis patient and was being treated for the same.

On extraoral examination, a diffuse, nontender, and firm swelling, measuring approximately 5 cm × 4 cm, was seen on the left side of the face, extending mediolaterally from ala of the nose to tragus of the ear and superoinferiorly from the infraorbital margin to 1 cm above the angle of the mouth. On palpation, the swelling was nontender and firm, and the surface was smooth with the overlying skin stretched. No discharge was noted from the left nostril [Figure 1]. Both the submandibular lymphnodes were slightly enlarged and thus palpable. Intraoral examination exhibited partial obliteration of the upper left buccal vestibular sulcus from 23 to 27 region, chronic generalized periodontitis, and heavy deposits of calculus and stains [Figure 2].
Figure 1: Diffuse swelling on the left side of the face

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Figure 2: Partial obliteration of the upper left buccal vestibular sulcus from 23 to 27 region, chronic generalized periodontitis, and heavy deposits of calculus and stains

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Routine paranasal sinus (PNS) or Water's view radiograph showed haziness of the left sinus with erosion of the antral wall on the lateral aspect [Figure 3]. Further, a computed tomography (CT) scan was advised which showed a homogeneously enhancing soft-tissue density (mass) in the anterior wall of the left maxilla, extending into the maxillary sinus and minimally into the orbital area. The lesion was also seen extending inferiorly till the maxillary alveolus with involvement of the buccinator muscle. The anterior wall of maxilla and orbital floor exhibited signs of destruction [Figure 4]. Chest X-ray findings did not show any abnormality.
Figure 3: Routine paranasal sinus or Water's view radiograph showing haziness of the left sinus with erosion of the antral wall on the lateral aspect

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Figure 4: Computed tomography scan showing a homogeneously enhancing soft-tissue density in the anterior wall of the left maxilla, extending into maxillary sinus and minimally into orbital area with signs of destruction of the anterior wall and orbital floor

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A routine blood test showed a normal erythrocyte sedimentation rate level of 28 mm/hr, a raised random blood sugar level of 224 mg/dl of blood, and a slightly elevated white blood cell count of 11,800/mm3.

With these findings, a provisional diagnosis of a long-standing antral polyp with chronic sinusitis with a differential diagnosis of a granulomatous condition or a low-grade sinonasal malignancy was thought of. An incisional biopsy was planned under local anesthesia. Fragments of soft-tissue specimen, cream to brown, firm, measuring approximately 1 cm × 1.5 cm, were received for histopathological examination. Hematoxylin and eosin (H and E)-stained sections showed well-formed granulomas composed of central eosinophilic caseation necrosis, surrounded by macrophages (few epithelioid cells), lymphocytes, neutrophils, and plasma cells, with focal areas of vasculitis separated by fibrous connective tissue septae [Figure 5]. Occasional multinucleated giant cells of Langhans type and some forming giant cells were seen [Figure 6]. These granulomas were seen infiltrating between the surrounding skeletal muscle bundles and adipose tissue. Focal areas of hemorrhage and muscle degeneration were also observed.
Figure 5: Hematoxylin and eosin-stained sections showing well-formed granulomas composed of central caseation necrosis (single arrow) and some forming giant cells (double arrows), separated by fibrous connective tissue septae and surrounded by chronic inflammatory cells (×5)

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Figure 6: Hematoxylin and eosin-stained sections showing granulomas with macrophages (epithelioid cells), lymphocytes, focal areas of vasculitis, and occasional multinucleated giant cells of Langhans type (single arrow) (×20)

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The pathologic findings were consistent with a granulomatous disease, probably a tuberculous granuloma. Thus, further sections were stained for acid-fast bacilli, and the stain failed to reveal any tuberculous bacilli, but, on the contrary, broad ribbon-shaped pauciseptate hyphal structures, some with right angle branching, were noted [Figure 7]. Further, Grocott methenamine silver (GMS) stain confirmed these hyphal elements to be mucor organisms [Figure 8]. A confirmatory diagnosis of mucormycosis-rhinocerebral (RCM) type was given. The patient was advised amphotericin-B 1 mg/kg body weight/day for 6 weeks. Further, the patient did not report back and hence was lost to further clinical follow-up and treatment.
Figure 7: Acid-fast bacilli stain showing broad ribbon-shaped pauciseptate hyphal structures (single arrow), some with right angle branching (×40)

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Figure 8: Grocott methenamine silver-stained section showing the ribbon-shaped, pauciseptate dark brown hyphal structure with acute angle branching (single arrow) (×40)

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  Discussion Top

Mucormycosis are infections caused by the fungi of the class Zygomycetes, comprised of the orders Mucorales and Entomophthorales.[6] These fungi are ubiquitous, being found commonly in decaying vegetation, soil, and moldy bread.[7] They are characterized by broad hyphae and nearly septations. Paultauf first described this disease in his article entitled “Mycosis mucorina” in 1885, though their ability to cause disease in humans dates back to 1800.[8] The pathophysiology of zygomycosis is not completely understood, but certain mechanisms are proposed which involve both innate and adaptive immune responses [Figure 9].[1]
Figure 9: Pathophysiology of mucormycosis (Adopted from Odessey et al. 2008)

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Conditions that predispose to mucormycosis include diabetes with ketoacidosis, immunosuppressive therapy with cytotoxins or the use of long-term corticosteroid therapy, use of deferoxamine for the treatment of iron overload, hematological malignancies such as leukemia and lymphoma, recipients of hematopoietic cell and solid organ transplantation, acquired immunodeficiency syndrome, traumatic implantation of soil, maceration of skin by a moist surface, burns, direct access through intravenous catheters or subcutaneous injections (intravenous drug abuse), and malnutrition.[9],[10]

Clinical manifestations differ depending on the site of invasion. Reported sites of infection include the nose, lungs, gastrointestinal tract, skin, kidneys, and central nervous system. Five major clinical forms thus exist, i.e. the (i) RCM, (ii) pulmonary, (iii) cutaneous, (iv) gastrointestinal, and (v) disseminated [Table 1].[11]
Table 1: Relationship between predisposing condition and site of infection

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RCM is the most recognized form of this disease because of its severity and occurs with or without oral manifestations. The process originates in the PNS as a result of inhalation of airborne spores which spread to involve the nose, eye, and brain, invading blood vessels and destroying cranial nerves. Progression is very rapid, and dissemination to the brain may be fatal.[12] Infections that extend from sinuses into the mouth produce painful, black necrotic ulcerations (eschars) of the hard palate (the most common). Ulcers on gingiva, lip, and alveolar ridge have also been reported.[13]

Our patient manifested with a sinus problem with destruction of the anterior portion of the antral wall to some extent, but no sequestration was observed, and she remained free from the usually reported complications such as osteomyelitis, widespread sinus and adjacent bone involvement, blindness, cavernous sinus thrombosis, carotid artery thrombosis, jugular vein thrombosis, and cranial nerve paralysis. Hence, the case was provisionally diagnosed as an antral polyp with sinusitis/sinonasal malignancy/granulomatous condition.

On plain film radiography, mucormycosis was characterized by focal destruction of the bony walls of the nasal cavity, with hazy radiopaque shadow suggesting the soft-tissue densities in the sinuses. CT scan is contemplated as 100% sensitive with 78% specific modality, which is useful in the diagnosis of sinonasal mycosis. On CT scan, foci of hyperdensity in the affected sinus were highly suggestive of the fungal disease. On magnetic resonance imaging (MRI) scan, fungal infections often appear as hypointense areas, both on T1- and T2-weighted images. Our patient though showed sinus involvement (homodensity) along with destruction of adjacent bone on CT scan, there were no areas of hyperdensity in the affected sinus and also, she remained free from complications.

Upon visual inspection, infected tissues may appear normal during the early stages, but then, they progress through an erythematous phase with or without edema before the onset of violaceous appearance and finally after the development of a black, necrotic eschar, as the blood vessels become thrombosed and tissue infarction occurs.[14] Since it was a sinus infection and presented without any discharge, visual inspection of the infected tissue was not possible.

Definitive diagnosis rests on histopathologic examination of biopsied tissues. The hallmarks of this disease are angioinvasion, thrombosis, ischemia, and necrosis of the involved tissues. The organisms seldom stand out in the routine H and E-stained sections and usually appear as basophilic, wide, ribbon-like, aseptate or pauci-septate, hyaline hyphal elements with right angle branching, in the setting of extensive necrotic debris. Usually, these organisms are observed in the necrotic marrow tissue adjacent to the dead bony spicules of lamellated bone, exhibiting ischemic necrosis with a peripheral rim of neutrophils and hemorrhage.[12] However, in our case, an interesting finding was the well-formed granulomas with central necrosis resembling caseation necrosis and multinucleated giant cells mimicking Langhans giant cells. All these features in the absence of fungal organisms and with a history of chronic cough and family history of tuberculosis misled to the diagnosis of a granulomatous infection?? Tuberculosis. The paucity of fungi in the given specimens probably accounted for its nonappearance in H and E sections.

Owing to granulomatous presentation simulating tuberculosis, the tissue sections were further stained with acid-fast stain. Surprisingly, the broad pauciseptate fungal elements were revealed which were confirmed with GMS staining. Thus, the use of special stains such as GMS, periodic acid–Schiff, and Papanicolaou stains is recommended. Scrapings, sputum, and exudates are usually examined using 10%–20% potassium hydroxide, Parker Ink, or calcofluor mounts.[2]

Once diagnosed, immunosuppressive therapies are discontinued if possible, and amphotericin-B is initiated. Prognosis depends on the nature of the underlying disease. Absence of immunosuppression and ketoacidosis with a history of chronic sinusitis probably led to the development of a chronic granulomatous form instead of a life-threatening invasive infection in our case. This makes our case of mucormycosis unique. Despite repeated recalls, our patient did not report for subsequent follow-up sessions and further treatment.

  Conclusion Top

Paranasal mucormycosis at times can assume an indolent/chronic clinical presentation with a misleading family history and granulomatous appearance histologically as seen in our case. It is in such cases that our diagnostic versatility is put to test, and it becomes very vital to prevent complications or fatality. Apart from a CT or MRI scan aiding in diagnosis, the microscopic examination of the diseased tissue remains the gold standard for arriving at a final diagnosis, taken the help of special stains. Hence, every clinician must be aware of such a benign course and include it in the differential diagnosis of PNS diseases, especially in the setting of diabetes, as prognosis depends on early diagnosis.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/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.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Odessey E, Cohn A, Beaman K, Schechter L. Invasive mucormycosis of the maxillary sinus: Extensive destruction with an indolent presentation. Surg Infect (Larchmt) 2008;9:91-8.  Back to cited text no. 1
Soni A. Paranasal mucormycosis in an immunocompetent individual: Importance of early diagnosis. Int J Oral Health Med Res 2017;4:52-6.  Back to cited text no. 2
Angali RK, Jeshtadi A, Namala VA, Gannepalli A. Fatal rhino-orbito-cerebral mucormycosis in a healthy individual. J Oral Maxillofac Pathol 2014;18:460-3.  Back to cited text no. 3
[PUBMED]  [Full text]  
Ferguson BJ. Mucormycosis of the nose and paranasal sinuses. Otolaryngol Clin North Am 2000;33:349-65.  Back to cited text no. 4
Navya BN, Vivek TG, Sudhir KT, Shwetha VP, Ahalya R. Role of histopathology in the diagnosis of paranasal fungal sinusitis. J Dent Med Sci 2015;14:97-101.  Back to cited text no. 5
Chakravarti A, Mishra M. A rare case of rhinofacial zygomycosis due to conidiobolus infection. Otorhinolaryngol Clin Int J 2014;6:65-7.  Back to cited text no. 6
Palejwala SK, Zangeneh TT, Goldstein SA, Lemole GM. An aggressive multidisciplinary approach reduces mortality in rhinocerebral mucormycosis. Surg Neurol Int 2016;7:61.  Back to cited text no. 7
[PUBMED]  [Full text]  
Viterbo S, Fasolis M, Garzino-Demo P, Griffa A, Boffano P, Iaquinta C, et al. Management and outcomes of three cases of rhinocerebral mucormycosis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2011;112:e69-74.  Back to cited text no. 8
Rai S, Misra D, Misra A, Jain A, Jain P, Dhawan A, et al. Palatal mucormycosis masquerading as bacterial and fungal osteomyelitis: A rare case report. Contemp Clin Dent 2018;9:309-13.  Back to cited text no. 9
[PUBMED]  [Full text]  
Herbrecht R, Letscher-Bru V, Bowden RA, Kusne S, Anaissie EJ, Graybill JR, et al. Treatment of 21 cases of invasive mucormycosis with amphotericin B colloidal dispersion. Eur J Clin Microbiol Infect Dis 2001;20:460-6.  Back to cited text no. 10
Spellberg B, Edwards J Jr., Ibrahim A. Novel perspectives on mucormycosis: Pathophysiology, presentation, and management. Clin Microbiol Rev 2005;18:556-69.  Back to cited text no. 11
Shetty SR, Punnya VA. Palatal mucormycosis: a rare clinical dilemma. Oral Surg 2008;1:145-8.  Back to cited text no. 12
Jayachandran S, Krithika C. Mucormycosis presenting as palatal perforation. Indian J Dent Res 2006;17:139.  Back to cited text no. 13
[PUBMED]  [Full text]  
Sahota R, Gambhir R, Anand S, Dixit A. Rhinocerebral mucormycosis: Report of a rare case. Ethiop J Health Sci 2017;27:85-90.  Back to cited text no. 14


  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8], [Figure 9]

  [Table 1]


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