Clinicopathological and immunohistochemical analysis of plasma cell gingivitis- A retrospective study

Abstract

Background:

This study aims to describe the demographics and clinicopathological characteristics of the cases of plasma cell gingivitis (PCG) reported in our institute, supported by a review of pertinent literature. Further, we investigated the role of the cluster of differentiation CD138, Ki67, CD56, and CD117 immunoexpression in the differential diagnosis of PCG from plasma cell dyscrasias.

Materials and Methods:

All histopathologically confirmed cases of PCG, whose relevant details could be obtained, were included in this study. They were subjected to panel of immunohistochemical markers to exclude plasma cell malignancies. Further, published English literature for PCG since 1970–2020 was reviewed.

Results:

Nine histopathologically confirmed cases of PCG, were retrieved from the archives of our department. The cases comprised 3 males and 6 females with their ages ranging between 14 and 82 years. The plasma cells exhibited equivocal reactivity for kappa and lambda; and immunonegativity for CD56, CD117 with low Ki67 proliferation index. Published literature in English showed 43 cases of PCG were predominantly female; the diffuse involvement of maxilla and mandible was a common finding.

Conclusion:

In addition to kappa lambda reactivity, an immunoprofile of CD138, Ki67, CD56, and CD117 may be used as a diagnostic adjunct to exclude malignant plasma cell lesions in confusing cases.

INTRODUCTION

Plasma cell gingivitis (PCG) is a rare benign lesion of the gingiva with various appellations such as plasma cell gingivostomatitis, idiopathic gingivostomatitis, etc.[1,2] The latest 2017 World Workshop classification has included this entity under nonplaque induced gingival lesions though the previous editions have expanded its classification under conditioned gingival enlargement.[3] The predisposing factors responsible are allergic reactions to some known allergens though in the majority of the cases the cause remains unidentified.[4] Thus, PCG is classified into 3 categories; caused by allergens, neoplasms, or unknown cause.[5,6]

There is no particular age or sex distribution for PCG except female predominance in few.[7] Clinically it usually presents as diffuse, red, edematous enlargement of the marginal gingiva extending into attached gingiva with sharp demarcation along the mucogingival border.[8] Many a times, PCGs are associated with other mucosal lesions such as cheilitis and glossitis.[9] Microscopy shows diffuse intense infiltration of mature plasma cells in the stroma with marked epithelial changes.[4,10,11] PCG mimics other immune-mediated mucous lesions and sometimes plasma cell dyscrasias (PCDs). Thus, in complex cases, a multidisciplinary diagnostic approach involving clinical and microscopic features along with diagnostic adjuncts such as hematology and immunohistochemistry (wherever required) is often necessary. However, the role of immunohistochemistry is not extensively studied in the diagnosis of PCG so far.

CD138 (syndecan) is a marker of plasma cells irrespective of reactive or neoplastic nature. Kappa and lambda light chain reactivity is commonly used to study the clonality of plasma cells.[9] CD56 is neural cell adhesion molecule which is expressed in 70%–80% of malignant plasma cells.[12] CD117 is hematopoietic growth factor which is observed in 33% of plasma cell myeloma (PCM) patients. However, the lack of expression of these markers in malignant plasma cell neoplasms indicates more aggressive behavior. Nevertheless, normal plasma cells are typically negative for both CD56 and CD117.[13] Ki67 is well-known cell proliferation marker related to aggressive biological behavior.[14] Mukherjee et al. studied the expression of CD44, CD34, CD43, Ki67, and CD117 in addition to kappa lambda profile in discrimination of PCG from malignancies.[15] However CD56 expression is not yet studied in PCG.

Thus, the aim of the present study was to retrospectively analyze clinico-pathological characteristics of PCG reported at a tertiary care dental hospital. We emphasize the conventional multidisciplinary approach integrating microscopic features with history, clinical and imaging details for reaching the accurate diagnosis. Further, the role of hematological investigations and immunohistochemical evaluation of CD138, CD56, CD117, Ki67, and kappa lambda in differentiating PCG from malignant neoplasms is also highlighted and the relevant literature is examined.

MATERIALS AND METHODS

After receiving institutional ethical approval and following Helsinki Declaration and their guidelines, we retrospectively reviewed 2044 biopsies received in the department of oral pathology and microbiology, from January 2018 to July 2020. The paraffin-embedded blocks of confirmed PCG cases were retrieved from the archives. All hematoxylin- and eosin-stained sections of PCG cases were analyzed. The pertinent details were retrieved from case files of patients. Periodic acid Schiff (PAS) stain was used to exclude candidiasis. To rule out overt malignancies and to confirm the polyclonal nature of plasma cells, immunohistochemistry with Ki67, CD56, CD117, CD138, Kappa, and lambda were performed for each case. These cases were re-evaluated by the pathologists and the final diagnosis of PCG was confirmed.

For the literature review, we conducted an extensive search of published English literature from 1971 to 2020 using PubMed and Google Scholar as the primary databases. The MeSH terms used were PCG, gingiva, idiopathic enlargement, maxilla, and mandible. The cases previously reported were compared with our series of PCG.

RESULTS

The study included 9 histopathological confirmed cases of PCG comprising 6 females and 3 males (M:F ratio-1:2). The age range was 14–82 years with a mean age of presentation being 45.3 years [Table 1; Figure 1].

Table 1.

Clinical features of plasma cell gingivitis in our study

Clinical details	Case 1	Case 2	Case 3	Case 4	Case 5	Case 6	Case 7	Case 8	Case 9
Gender, age (years)	Female, 26	Male, 34	Female, 82	Female, 14	Female, 26	Female, 63	Female, 24	Male, 67	Male, 46
Location	Maxilla and mandible	Maxilla and mandible	Mandible	Maxilla and mandible	Maxilla and mandible	Maxilla	Maxilla	Mandible	Maxilla and mandible
Clinical presentation	Generalized gingival enlargement	Swollen erythematous mass	Erythematous proliferative lesion	Generalized gingival enlargement	Generalized gingival enlargement	Localized gingival erythematous swelling	Diffuse gingival ulceration	Localized buccal erythematous swelling	Generalized gingival enlargement
Radiographic findings	-	-	-	-	Generalized horizontal bone loss	-	-	-	-
Etiological factor	UI	UI	Implant supported prosthesis	UI	UI	UI	UI	UI	UI
Treatment	Gingivectomy	Gingivectomy	Surgical excision	Gingivectomy	Gingivectomy	Surgical excision	Surgical excision	Surgical excision	Gingivectomy

UI - Unidentified

Figure 1.

Clinical presentation of plasma cell gingivitis. (a) Extra-oral picture showing facial asymmetry. (b) Preoperative generalized gingival enlargement (frontal view). (c) Preoperative gingival enlargement (occlusal view). (d) Postoperative view after 6 months of surgical excision of enlarged gingiva (e) Orthopantomogram showing generalized bone loss

Predisposing factors remain unidentified in all except one case where there was associated implant-supported prosthesis adjacent to the lesion. Clinical differential diagnosis included idiopathic gingival enlargement, PCG, granulomatous diseases, mucocutaneous lesions, pyogenic granuloma, and rarely malignancies, namely leukemia, extramedullary plasmacytoma (EMP), and PCM. Normal hematological profile ruled out leukemia and lupus erythematosus.

Microscopy of the cases characteristically exhibited intense plasma cell infiltrates (>50%–70%) within vascular stroma with no cellular atypia and variable epithelial changes [Figure 2].

Figure 2.

Histopathological presentation of plasma cell gingivitis. (a) Spongiotic hyperplastic epithelium overlying inflamed stroma (inset showing psoriasiform hyperplasia). (b) Epithelium showing marked acanthosis and leucocytic exocytosis (red arrow). (c) Epithelium exhibiting hyperplasia with entrapped fibrovascular cores and spongiosis. (d) Acanthosis and plasma pooling within epithelium. (e) Stroma exhibiting intense inflammatory infiltrate with interspersed engorged blood vessels. (f) High power showing predominantly plasma cells exhibiting eccentric nuclei

Epithelial characteristics

All cases were circumscribed showing epithelial covering focally with predominant areas of ulceration. All cases displayed hyperplasia, acanthosis, spongiosis while some cases showed arcading pattern (Case 2, 5, and 9) and plasma pooling (Case 6). All cases showed parakeratinization, while 4 (Case 4, 5, 7, and 8) cases showed loss of keratinization in few areas. Only 4 cases showed leukocyte exocytosis (Case 1, 2, 5, 7).

Connective tissue characteristics

There was an intense infiltration of plasma cells predominantly arranged in sheets and lobules while few cases (1, 2, and 8) showed diffuse arrangement. All the cases showed mild-to-moderate vascularity with engorged blood vessels. In addition, Case 8 showed histiocytes and multinucleated giant cells.

Histopathological differentials considered were PCG, IgG4 related disease (RD), and PCDs such as plasmacytoma and its multicentric form-PCM [Table 2]. Immunohistochemically, plasma cells in all the cases showed mixed reactivity for both Kappa and lambda (kappa lambda ratio of 1:01) confirming a polyclonal nature. These cells were negative for CD117, CD56, PAS; immunopositive for CD138 and exhibited low to negative Ki67 proliferation index (1%–4%) [Figure 3]. The published literature showed 43 reported cases of PCG from 1971 to 2020 [Supplementary Table 1].[1,4,5,6,7,9,11,15,16,17,18,19,20,21,22,23,24,25,27,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48]

Table 2.

Differential diagnosis of Plasma cell gingivitis

	Clinical differentials		Histological differentials
	Cicatricial pemphigoid (CP) discoid lupus erythematosus	Pyogenic granuloma	Oral lichen planus	Plasma cell dyscrasias		IgG4^ related disease
				Extramedullary plasmacytoma	Plasma cell Myeloma with extramedullary involvement
Clinical entity presenting granulomatous overgrowth	Mucocutaneous lesions, vesicles, Nikolsky's sign	Pedunculated lesion involving gingiva most frequently	Bilaterally symmetrical lesion involving skin, buccal mucosa most frequently	Head and Neck most common, Soft tissue mass	Local growth of soft tissue in vicinity to skeleton or hematogenous spread to any other organ or tissue	Heterogeneous clinical and radiological presentation which mimics malignancy.
Histology	Subepithelial split with variable inflammation in CP* Hyperkeratosis, follicular plugging, degeneration of basal cells	Abundant engorged blood vessels in the background of mixed inflammatory infiltrate	Saw toothed rete ridges, liquefactive degeneration of basal layer with intense lymphocytic infiltrate subepithelially	monoclonal plasmacytoid cells with light chain restriction	Similar to plasmacytoma, acquire blastoid morphology in plasmablastic plasma cell myeloma	Storiform fibrosis, obliterative phlebitis and more than10/high power field IgG4 positive plasma cells (more specifically ratio of IgG4 to IgG positive plasma cells as >0.4)
Treatment	Systemic corticosteroid, immunomodulator therapy	Conservative surgical excision	Symptomatic cases require variable treatment ranging from topic corticosteroids to antifungal or systemic steroids or immunomodulators	Radiation therapy	Chemotherapy	Corticosteroids
Prognosis	Generally good, spontaneous remission in 2-5 years	Excellent, occasional recurrence	Malignant potential controversial	Better prognosis than solitary plasmacytoma, 30% patient progress to PCM#	Usually incurable progressive disease, median survival rate 5.5 years	Irreversible injury to some organs if therapy is not initiated in time, once fibrosis is established treatment options are limited

CP - Cicatricial pemphigoid, PCM - Plasma cell myeloma, IgG - Immunoglobulin G

Figure 3.

Special staining and immunoprofile of plasma cell gingivitis. (a) Periodic acid–Schiff staining showing no fungal organisms. (b) Plasma cells exhibiting membranous and cytoplasmic cluster of differentiation 138 immunopositivity. (c) Ki67 proliferation index less approximately 1%. (d and e) Plasma cells displaying immunonegativity for CD117, CD56. (f and g) plasma cells displaying equivocal immunoreactivity for kappa and lambda light chains

Supplementary Table 1.

Literature review of histopathologically confirmed cases of plasma cell gingivitis from 1971 to 2020

Author, year	Gender, age	Location	Predisposing factor	Clinical presentation	Clinical and laboratory investigations	Special stains and immunohistochemistry	Treatment	Follow up
Kerr DA et al., 1977##	-	-	-	-	-	-	-	-
Palmer RM et al., 1981	Female, 29	Maxilla	UI	Swollen upper anterior gingiva	NHP^^	Cytology negative for candidal hyphae	Topical triamcinolone in orabase	2 years, NR
Palmer RM et al., 1981	Male, 52	Maxilla	UI	Swollen upper anterior gingiva	NHP	Special stains negative for fungal hyphae	Topical triamcinolone in orabase	2 years, NR
Serio FG et al., 1981	Female, 36	Maxilla and mandible	Red pepper	Severe gingival inflammation	NHP, negative Nikolsky's sign	Nonsurgical periodontal therapy	1 month
Newcomb GM et al., 1982*	Female, 12	Maxilla and mandible	UI	Erythema, gingival enlargement	-	-	Gingivectomy	2 year
D'Angelo M et al., 1983##	-	-	-	-	-	-	-	-
Maioli S et al., 1984##	-	-	-	-	-	-	-	-
Lubow RM et al., 1984	M,36	Maxilla	Dynamints	Ulcerated marginal gingiva	History of psoriasis, NHP except increased eosinophils	NA	Gingivectomy	8 months, NR
Macleod RI et al., 1989**	-	-	Herbal toothpaste	-	-	-	-	-
Timms MS et al., 1991	Female, 70	Maxilla and mandible	UI	Gingival erythema and laryngeal lesions	Supraglottic laryngeal involvement	Positive reactivity for kappa and lambda light chains and various heavy chains	Systemic steroids	Long term
Timms MS et al., 1991	Female, 32	Maxilla and mandible	UI	Gingival erythema and laryngeal lesions	Supraglottic laryngeal involvement	Positive reactivity for kappa and lambda light chains and various heavy chains	Systemic steroids	Long term
Timms MS et al., 1991	Female, 57	Maxilla and mandible	UI	Gingival erythema and laryngeal lesions	Supraglottic laryngeal involvement	Positive reactivity for kappa and lambda light chains and various heavy chains	Systemic steroids	Long term
Nitta H et al., 1991*	-	-	UI	Gingival enlargement	-	-	Conventional periodontal therapy	-
Sollecito TP et al., 1992	Female, 61	Maxilla	UI	Erythematous gingiva	NHP, negative lupus band test and ANA antibodies	Non-specific immunofluorescence, cell marker analysis suggestive of reactive infiltrate	Topical steroids	3 weeks, remission
Sollecito TP et al., 1992	Female, 62	Maxilla	UI	Erythematous gingiva	NHP	NA	Topical steroids	3 weeks, remission
Reed BE et al., 1993	Female, 37	Maxilla and mandible	UI	Generalized swelling	NHP	Direct and indirect immunofluorescence revealed reactive plasma cells	Conventional periodontal treatment	-
Gargiulo AV et al., 1995*	-	-	-	-	-	-	-	-
Mahler V et al., 1996	Female, 53	Maxilla	UI	Erythematous maxillary gingiva	NA	90% IgG producing plasma cells, Special stains negative for fungal hyphae, positive reactivity for kappa and lambda	Topical 2% fusidic acid	10 weeks, resolution
Marker P et al., 2002	Male, 30	Mandible	Khat	Erythematous gingiva	Marked bone destruction on imaging	PAS negative for fungal hyphae	Nonsurgical periodontal therapy	2 weeks, remission
Roman CC et al., 2002	F,13	Maxilla	UI#	Erythematous gingiva	Low serum and secretory IgA, other hematological and biochemical tests normal	PAS negative, positive reactivity for kappa and lambda	electrocoagulation	2 years, NR
Velez et al., 2005*	-	-	Kitchen cleaning solution	Erythema, enlargement	-	-	-	-
Anil S et al., 2007*	Male, 26	-	-	Inflamed gingiva	NHP	-	Nonsurgical periodontal treatment	1 to 2 weeks, remission
Anil S et al., 2007*	Male, 27	--	-	Inflamed gingiva	NHP	-	Nonsurgical periodontal treatment	1 to 2 weeks, remission
Anil S et al., 2007*	Male, 36	-	-	Inflamed gingiva	NHP	-	Nonsurgical periodontal treatment	1 to 2 weeks, remission
Bhatavadekar N et al., 2008	Female, 17	Maxilla	UI	Erythematous gingiva	Periapical imaging normal	-	Surgical excision	-
JadwatY et al., 2008*	Female, 19	-	-	-	-	-	-	-
Bali D et al., 2012	Female, 48	Maxilla	Colocasia leaves	Generalized diffuse gingivitis	NHP	NA	Surgical excision	2 weeks, NR
Lamdari N et al., 2012*	Female, 29	-	Herbal dentifrice	Erythematous gingiva	-	-	Nonsurgical periodontal therapy and discontinuation of herbal dentifrice	1 month, remission
Wood NH et al., 2012§	Female, 70	Maxilla and mandible	UI	Generalized gingival enlargement		-	Gingivectomy	-
Janam P et al., 2012	Female, 15	Maxilla and mandible	UI	Generalized gingival enlargement	NHP, NBP	NA	Gingivectomy	8 months, Mild recurrence
Makkar A et al., 2013	Female, 17	Maxilla and mandible	Acacia Arabia (herbal extract)	Gingival enlargement with bone loss	NHP, progressive bone loss on imaging	NA	Gingivectomy	Recurrence after 1 year
Abhishek K et al., 2013	Male, 16	Maxilla and mandible	UI	Gingival enlargement	NHP, NBP	NA	Gingivectomy	1 year, NR
Kumar V et al., 2014	Male, 42	Maxilla	UI	Localized swelling in the upper anterior jaw	NHP and severe alveolar bone loss in radiographs	Positive reactivity for kappa and lambda	Surgical excision	6 months, NR
Joshi C et al., 2014	Male, 27	Mandible	Herbal toothpowder	Bleeding swollen mass	Negative Nikolsky's sign, NHP	NA	Gingivectomy	3 months, NR
Ranganathan AT et al., 2015	Male, 20	Maxilla	UI	Enlarged maxillary anterior gingiva	Nikolsky's sign negative, NHP	NA	Topical chlorpheniramine maleate	10 months, NR
Mishra MB et al., 2015*	Female, 15	-	Herbal agents in dentifrices	-	-	-	-	-
Mukherjee M et al., 2015	M,26	Maxilla and mandible	Possibly herbal toothpaste	Gingival enlargement	NHP, negative Nikolsky's sign	CD34, CD117, Ki67, CD43 negative, CD44 positive, positive reactivity for kappa and lambda (10:1)	Gingivectomy	2 years, NR
Prasanna JS et al., 2016	Female, 19	Maxilla and mandible	Fixed partial denture	Gingival enlargement	NHP	NA	Gingivectomy	6 months, NR
Prasanna JS et al., 2016	Male, 15	Maxilla and mandible	UI	Gingival enlargement	NHP	NA	Gingivectomy	6 months, NR
Negi BS et al., 2019	Male, 12	Maxilla and mandible	UI	Gingival enlargement and erythema	NHP	Positive reactivity for kappa and lambda	Laser assisted gingivectomy	3 years
Chauhan Y et al., 2019	Male, 18	Maxilla and mandible	UI	Gingival enlargement with cheilitis	Negative Nikolsky's sign, NHP	Positive reactivity for kappa and lambda	Gingivectomy	8 months, NR
Barbe AG et al., 2020	Male, 33	Maxilla and mandible	UI	Gingival enlargement	Microcytic erythrocytosis, no anemia, deficiency of Vitamin D and folic acid, electrophoresis showed sickle cell anemia	Positive reactivity for kappa and lambda, IgG4/IgG: 0.279	Gingivectomy	6 months, NR
Vishnu V et al., 2020	Female, 13	Maxilla		Diffuse gingival enlargement	NHP and crestal bone loss in radiographs, AFB; negative, calcium, ACE enzyme levels, cANCA, chest radiograph normal**	NA	Gingivectomy	1 year

*Only abstract available full article not accessible; **This case showed foreign body giant cells and granuloma formation histologically along with intense plasma cell infiltrate. Thus, granulomatous diseases such as tuberculosis, sarcoidosis, Wegener granulomatosis were considered as differentials and were ruled out by AFB negativity, normal ACE and calcium levels; normal chest radiograph and cANCA levels respectively; ^#Thought to be chewing gum associated but on discontinuation of its usage lesion did not disappear and after surgical treatment usage of chewing did not cause recurrence of lesion; ^##No abstract available; ^§This was the case of concomitant PCG with diffuse peripheral odontogenic fibroma. UI - Unidentified; NHP - Normalhematological profile; NR - No recurrence; NA - Not accessed; AFB - Acid-fast bacilli; ACE - Angiotensinconvertase enzyme; cANCA - Antineutrophilic cytoplasmic antibodies; NBP - Normal biochemical profile; ANA - Antinuclear antibody; Ig - Immunoglobulin; PAS - Periodic acid-Schiff; CD - Cluster of differentiation; M - Male; F - Female

DISCUSSION

In the present study, 9 cases of PCG were diagnosed in the last 3 years as compared to only 43 cases reported in the literature in the last 50 years. It can be explained by two reasons. First, it can be suggested that the low number of PCG cases is a result of under-reporting since the entity is not novel, also since only literature in English were searched and included in the manuscript, case reports in other languages were most likely overlooked. Another reason for increased frequency of PCG in our institute can be attributed to the fact that our center is an apex referral center. PCG does not always respond well to the treatment prescribed due to unidentifiable etiological factors in most situations. Hence, the patients are generally referred to higher centers for the relief of symptoms.

The analysis of the published literature revealed female predominance with male-to-female ratio of 1:1.42. The age ranged from 12 to 70 years (mean 31.6) and presentation in the pediatric age group was rare. The maxillary lesions were more common, involving the anterior gingiva in the majority of cases. The herbal toothpaste and their ingredients were recognized as risk factors in most of the cases. Clinical appearance varied from gingival enlargement (18 cases), followed by the erythematous lesion (13 cases), ulcerated swollen mass (6 cases), and gingival inflammation (6 cases).

Upon comparing the characteristic features of PCG in the published literature with our cases, similarities were observed in sex predilection where a female predominance was demonstrable, with involvement of maxillary and mandibular arch more frequently than tongue, lip, and palate.[4,17,18] The predisposing risk factors remained unidentified in the majority of the cases in literature which is concurrent with our observations. Some reports have found herbal agents in dentifrices,[19,20] Khat leaves,[21] colocasia (arbi) leaves,[1] mint,[22] fixed prosthesis, and dietary components as contributing factors. The lesions get eventually resolved by identifying the risk factor and eliminating it from the patient diet.[3] Unfortunately, in our series, the predisposing factor remains unidentified except for one case where the prosthetic component proved to be risk factor for PCG. This was consistent with the case reported by Prasanna et al.[23]

PCG clinically mimics other reactive lesions such as pyogenic granuloma, peripheral giant cell granuloma, immune-mediated mucous lesions such as cicatricial pemphigoid and discoid lupus erythematosus and histologically mimic PCDs and IgG4 RD.

Clinically the current cases showed generalized gingival enlargement involving marginal and attached gingiva with altered contour and rolled out margins that is identical to the case reported by Vishnu et al.[7] Diffuse swollen erythematous mass and gingival ulceration were observed which are consistent with previous reports.[24,25] Radiographic finding of generalized horizontal bone loss was seen in a single case as mentioned in the literature.[15] Silverman has described syndromic association with the triad of PCG, glossitis, and cheilitis but no case in our series showed this association.[26] Three cases in the literature were associated with supraglottic lesions but none of our present cases showed laryngeal lesions.[27] Similarly, Tandon et al. reported a case of oral tuberculosis that mimicked PCG on incisional biopsy, however, chest radiograph and excisional biopsy confirmed it to be tubercular gingivitis.[28]

Few isolated case reports have mentioned plasma cell granuloma as a manifestation of underlying IgG4- RD (IgG4-RD).[29] IgG4-RD is a rare fibro-inflammatory systemic disease with comprehensive diagnostic criteria which is a combination of clinical, imaging, laboratory, and histopathological findings.[30,31] None of our present cases could fulfill the diagnostic criteria for IgG4-RD and thus this differential was excluded.

Barbe et al. have reported a case of sickle cell anemia mimicking PCG the diagnosis of which was confirmed by altered hematological profile and electrophoresis.[16] Histopathological examination showed diffuse intense infiltrate of plasma cells in the subepithelial connective tissue with no evidence of cytological atypia. Vishnu et al. reported a case of PCG mimicking granulomatous disease.[7] Polyclonal nature of plasma cells was confirmed by kappa lambda light chain co-expression is most of the cases.

Further PCDs should be excluded before labeling a lesion as reactive PCG.[3] PCDs, are malignant neoplasms of monoclonal plasma cells exhibiting metastatic potential. Solitary plasmacytoma of bone is unicentric malignancy with origin within bone whereas EMP is predominantly seen in the head–and-neck region. PCM is systemic malignancy with multicentric origin within the bone with the same histopathology as plasmacytoma but poorer prognosis.[3,32,33] As both reactive and neoplastic plasma cells exhibit CD138 immunopositivity, the restriction in production of one of the two (kappa and lambda) light chains is a promising way to confirm monoclonality.[3] Immunonegativity to CD117, CD56, low to negative Ki67proliferation index, and equivocal reactivity for kappa and lambda in all the present cases of PCG was in accordance with Mukherjee et al.[15] However, CD56 was evaluated for the first time in PCG. The results were in agreement with the published data which showed CD56 immunonegativity in normal plasma cells.[14]

The treatment in all cases of our study constituted gingivectomy followed by Phase I therapy and surgical excision of the lesion. Recurrence was observed in only 1 case till 2 years of follow-up (Case no. 4). However, in literature, different treatment modalities of PCG exist including nonsurgical and surgical approaches [Supplementary Table 1]. Nonsurgical treatments comprise oral and topical steroids, topical 2% fusidic acid, topical chlorpheniramine maleate, and strict elimination of recognized risk factors; surgical approach advocates gingivectomy and surgical excision.

CONCLUSION

Our study explained in detail the clinicopathological features of PCG in comparison with literature findings. Further, it can be concluded that histopathology remains the gold standard to diagnose PCG. Immunonegativity for CD56, CD117, and low Ki67 proliferation index may be used as adjunctive diagnostic characteristic (in addition to already established kappa and lambda reactivity) for differentiating it from malignant PCDs. However, instead of the small number of cases of PCG in our study, these markers should be performed on a large sample size to confirm our findings.