Diagnosis Of Polymorphous Low-grade Adenocarcinoma Research Articles

POLYMORPHOUS LOW-GRADE ADENOCARCINOMA OF THE UPPER LIP: A CASE REPORT

A 49-year-old female patient presented with a nodule in the upper lip lasting 1 year. The patient had diabetes and had a 37-year smoking history (had quit 14 months before). On clinical examination, a firm, well-circumscribed submucosal nodule measuring 0.8 cm in diameter was observed in the upper lip, left side. Because it had mobility, an excisional biopsy was performed, under the clinical hypothesis of a benign neoplasm of salivary gland. Hematoxylin and eosin staining of the specimen was compatible with a malignant neoplasm of salivary gland. Immunohistochemical analysis showed positive staining for p63, S-100, CEA, CK and Ki-67, and a diagnosis of polymorphous low-grade adenocarcinoma was established. An investigation of the anatomical region with magnetic resonance imaging did not evidence remaining lesion. The patient has been under clinical and imaging follow-up for 5 years without any sign of recurrence of the neoplasm. A 49-year-old female patient presented with a nodule in the upper lip lasting 1 year. The patient had diabetes and had a 37-year smoking history (had quit 14 months before). On clinical examination, a firm, well-circumscribed submucosal nodule measuring 0.8 cm in diameter was observed in the upper lip, left side. Because it had mobility, an excisional biopsy was performed, under the clinical hypothesis of a benign neoplasm of salivary gland. Hematoxylin and eosin staining of the specimen was compatible with a malignant neoplasm of salivary gland. Immunohistochemical analysis showed positive staining for p63, S-100, CEA, CK and Ki-67, and a diagnosis of polymorphous low-grade adenocarcinoma was established. An investigation of the anatomical region with magnetic resonance imaging did not evidence remaining lesion. The patient has been under clinical and imaging follow-up for 5 years without any sign of recurrence of the neoplasm.

Plasmacytoid-Type Cellular Differentiation in Polymorphous Low-Grade Adenocarcinoma.

Polymorphous low-grade adenocarcinoma (PLGA) occurs more frequently in minor salivary glands. The diagnosis of PLGA, in general, is not difficult but in occasional tumors showing limited invasion or in small biopsy specimens, PLGA may be confused with cellular pleomorphic adenoma (PA). Plasmacytoid cells, a usual component of PAs, have been considered helpful for correct tumor identification. The aim of this study was to verify the frequency (if any) of plasmacytoid-type cellular differentiation (PD) in PLGA. Thirty-two cases of PLGA were reviewed. PD was recognized in 2 cases (6.25%), in which immunohistochemical expression of AE1/AE3, CK7, CK14, vimentin, α-SMA, p63, S-100, calponin, GFAP, and Ki-67 was evaluated. The 2 cases presented conventional areas of PLGA and variable quantities of cells with PD forming aggregates in the stroma and lining ductal structures. Cells with PD showed positivity for AE1/AE3, CK7, S-100, and vimentin and were negative for CK14, calponin, and GFAP in both cases. In case 1, cells with PD did not present α-SMA and p63 positivity whereas in case 2 they were positive, but for α-SMA such reactivity was restricted to cells forming solid aggregates. Although PD in PLGA is rare, it is necessary to be aware of this possibility, particularly in small incisional biopsies and in PLGA with limited invasion, to avoid confusion with cellular PA.

Doing more with less: the challenging diagnosis of polymorphous low-grade adenocarcinoma in incisional biopsy samples.

The diagnosis of polymorphous low-grade adenocarcinoma (PLGA) remains difficult for general pathologists, particularly in cases of small biopsy samples. We aimed to characterize the histopathological spectrum and immunohistochemical aspects by using an accessible immunohistochemical panel of cytoskeletal proteins in limited samples of PLGA. Forty-six patients diagnosed with PLGA in incisional biopsies were identified retrospectively. Seventy-two per cent of patients were women and 28% were men, with a mean age of 55 years. The palate was the most affected site. Grossly, the mean size of the samples was 0.8 cm and 74% of specimens were fragmented. All tumours characteristically displayed the microscopic features of architecturally diverse patterns, infiltrative areas and low-grade cytology. Neoplastic cells were diffusely positive to cytokeratin (CK) 7, vimentin and S100 protein, but only focally positive to CK14 and negative to α-smooth muscle actin (α-SMA), thus lacking myoepithelial differentiation. Microscopic recognition of PLGA is facilitated by a characteristic combination of multiple architectural patterns of growth, infiltration of adjacent tissues and cytological aspects. These features are present even in small biopsy samples. The association of histopathological aspects with CK7, CK14, vimentin, S100 and α-SMA immunoexpression is helpful in reaching the diagnosis of doubtful cases.

Polymorphous Low-Grade Adenocarcinoma

A 60-year-old woman with a 3-year history of a gingivoalveopalatal mass underwent an incision biopsy.
 Microscopically, the lesion centered in the stroma is infiltrative (Fig. 1) and architecturally diverse, having cystic (Fig. 2), linear or “Indian file” (Fig. 3), solid, and tubular (Fig. 4) patterns. The cells are uniform in size, round to oval, and have bland cytologic features, with vesicular nuclei and inconspicuous nucleoli (Figure 4). The clinical data and histomorphologic features characterized by architectural diversity yet cytologic blandness lead us to the diagnosis of polymorphous low-grade adenocarcinoma. 
 Polymorphous low-grade adenocarcinoma (PLGA) is a malignant epithelial tumor characterized by cytologic uniformity, morphologic diversity, an infiltrative growth pattern, and low metastatic potential.1 It is the second most common intraoral malignant salivary gland tumor 1 following mucoepidermoid carcinoma. The tumor is found almost exclusively in minor salivary glands and is rare in extraoral locations, including major salivary glands.2 The tumor affects a wide age range (16 – 95 years; mean 60 years), with only 2 pediatric cases reported,1 and has a female predilection.3,4 It usually presents as a painless mass located within the oral cavity,3 60% of which are located in the palate.1 They are characteristically unencapsulated, although well-circumscribed.3 
 
 This entity is architecturally diverse (“polymorphous”) even within a single tumor, with solid, tubular, trabecular, cribriform, papillary and linear patterns being described. Perineural invasion is common although it was not seen in this case. The tumor cells are small to medium sized, and uniformly round to polygonal. The nuclei are bland and vesicular, with occasional small inconspicuous nucleoli. Mitotic figures can be found occasionally but are never numerous.3, 8
 
 The morphologic heterogeneity in small biopsies and frozen section samples can be confused with pleomorphic adenoma and adenoid cystic carcinoma.6,7 Glial fibrillary acid protein may help as PLGA is typically non-reactive in contrast to pleomorphic adenoma.2 De Araujo and others site that uniformly positive vimentin, CK7, and S100 staining favors PLGA over adenoid cystic carcinoma.6 Tumor cytology and histology are quite characteristic - recognizing the constant cytological appearance despite the diversity of architectural tumor patterns should aid one in diagnosing PLGA.
 PLGA, despite its infiltrative growth pattern and propensity for perineural invasion, usually runs an indolent course. Nodal metastasis and distant spread are rare, occurring in less than 1% of cases.4 Seethala and others report that extrapalatal location is associated with a more aggressive clinical course.5 Complete surgical excision is the primary treatment with neck dissection reserved for nodal metastasis.1 One-third of patients may have a local recurrence and lifelong monitoring is suggested. Re-excision is amenable in these cases.5,6

口腔底ｐｏｌｙｍｏｒｐｈｏｕｓ ｌｏｗ ｇｒａｄｅ ａｄｅｎｏｃａｒｃｉｎｏｍａ例

Polymorphous low grade adenocarcinoma (PLGA) is a low grade malignant neoplasm mostly arising in the palate. We report a case of PLGA in the oral floor of a 60-year old man. He had an indolent tumor in the oral floor on the right side for about 30 years. Oral examination revealed a 4cm hard mass without mucosal ulceration. Since the tumor was thought to be benign, it was enucleated in the first surgery. Histological diagnosis was PLGA, as the tumor showed an infiltrative growth pattern without a capsule and a broad spectrum of architectural morphology including solid, tubular and cystic patterns. After the diagnosis of PLGA, an additional removal of the oral floor tissue and a dissection of the submandibular region on the right side were performed as the second surgery. The tumor has not recurred or metastasized in 6 months of follow-up, but close observation will continue.

Polymorphous low-grade adenocarcinoma of minor salivary glands: a study of 17 cases with emphasis on cell differentiation.

The diagnosis of polymorphous low-grade adenocarcinoma (PLGA) of salivary glands remains difficult for general surgical pathologists. In an effort to understand the morphological heterogeneity of these neoplasms and facilitate their recognition we reviewed the architectural patterns, cell differentiation and immunohistochemical features of 17 case of PLGA. There were 11 females and six males with a mean age of 58 years. Twelve tumours were located in the palate, two in the posterior third of the tongue, and one each in the upper lip, buccal mucosa and retromolar triangle. Two patients presented with neck metastases. The mean tumour size was 20 mm (range 6-50 mm). The tumour cells were arranged in five architectural patterns: tubules and small duct-like structures; cords and trabeculae; solid nests; cribriform areas and papillae. Twelve (71%) cases were composed of a combination of tubules and small duct-like structures, cords and trabeculae, and solid nests. Cribriform areas with pseudoluminal spaces were seen in six (35%) cases. A focal papillary pattern was evident in three cases and constituted 40% of the tumour in one. Perineural invasion was seen in 13 cases (76%). All cases studied were positive for CAM5.2, 34BE12, vimentin and S100 protein and showed overexpression of bcl-2 protein. Rb protein was present in 13 cases whereas p53 expression was absent in all cases. The average proliferation index (PI) was 7% (range 1-17%). Three patients developed local recurrences with cervical lymph node metastases but no patient died as result of tumour. No morphological features were found to be prognostic for the development of local recurrences or lymph nodes metastases. PLGA is a distinctive neoplasm of salivary glands formed by luminal and nonluminal tumour cells with limited patterns of architectural differentiation. The relative proportion of these cells seems to play a significant role in the morphogenesis of these tumours. The overexpression of the bcl-2 protein and the low PI suggest that inhibition of programmed cell death may be involved in the oncogenesis of PLGA.

Polymorphous low-grade adenocarcinoma: Glial fibrillary acidic protein staining in the differential diagnosis with cellular mixed tumors

Polymorphous low-grade adenocarcinoma is a recently recognized salivary gland carcinoma arising primarily within the oral cavity. Most of these tumors are readily diagnosed; occasionally, however, they may be confused histologically with cellular mixed tumors. The difficulty stems from the bland cytologic nature of cellular mixed tumors and their organizational diversity, together with the irregular pushing growth at their interface with adjacent soft tissues, on histologic examination. Because of this diagnostic problem, we evaluated the use of glial fibrillary acidic protein localization in the differential diagnosis of polymorphous low-grade adenocarcinoma and cellular mixed tumor. Twelve oral polymorphous low-grade adenocarcinomas (polymorphous low-grade adenocarcinoma) and twelve cellular mixed tumors were selected and stained for glial fibrillary acidic protein (glial fibrillary acidic protein) using a strept-avidin-biotin system and examined independently by each investigator. In addition, five tumors with limited material (three cellular mixed tumors and two polymorphous low-grade adenocarcinoma) from the consultation service of one author were evaluated using the same techniques. Two polymorphous low-grade adenocarcinoma stained positive in very focal areas and only in the epithelial component; staining did not occur in the stroma. Fourteen of fifteen mixed tumors focally to diffusely expressed glial fibrillary acidic protein. Only one tumor did not express glial fibrillary acidic protein. In mixed tumors with only focal staining, the most helpful differential diagnostic feature was positive staining of the mesenchyme-like cells adjacent to epithelial nests. We did not find this latter staining pattern in any of the polymorphous low-grade adenocarcinoma.