|Ahead of print publication
Histopathological and immunohistochemical features of 14 peritoneal mesotheliomas with clinical outcomes and recent updates
Srushti Karmarkar, Bharat Rekhi, Kedar K Deodhar, Santosh Menon
Department of Surgical Pathology, Tata Memorial Hospital, Homi Bhabha National Institute (HBNI), Mumbai, Maharashtra, India
|Date of Submission||02-Sep-2020|
|Date of Decision||17-Jun-2021|
|Date of Acceptance||08-Jul-2021|
|Date of Web Publication||16-Nov-2021|
Room Number: AB-818, Department of Surgical Pathology, 8th Floor, Annex Building, Tata Memorial Hospital, Dr E.B. Road, Parel, Mumbai 400 012, Maharashtra
Source of Support: None, Conflict of Interest: None
Background: Malignant peritoneal mesotheliomas (MPMs) are rare tumors with overlapping clinical and histopathological features, especially with epithelial ovarian carcinomas (EOCs). There is no substantial documentation on these rare tumors from our country.
Objective: To study the clinicopathological features including immunohistochemical (IHC) profile and clinical outcomes of 14 MPMs, diagnosed at our institution.
Materials and Methods: This was a retrospective study, wherein 14 cases of MPM, occurring in female patients, diagnosed at our institution, between January 2008 and May 2019 were included, after a critical review.
Results: Median age was 54.5 years. Most patients presented with ascites, omental nodularity, and fat stranding. Microscopically, most cases (11, 78.6%) displayed epithelioid morphology, followed by biphasic pattern (2, 14.3%) and a single case of well-differentiated MPM. IHC, diagnostic sensitivity and specificity of calretinin were 100% (13/13) and 85.7%; of HBME1 were 100% (5/5) and 100%; and of podoplanin (D2–40) were 60% (2/5) and 100%. Other positively expressed immunomarkers were epithelial membrane antigen (n = 2/5, 40%), cytokeratin 5/6 (n = 4/4, 100%), and WT1 (n = 9/10, 90%). Most patients (5/12, 41.7%) were treated with chemotherapy. The 3-year disease-free and overall survival rates were 25.7% and 54%, respectively, including improved survival trend in patients with epithelioid type of MPMs.
Conclusion: MPMs are diagnosed with a combination of clinicopathological features and optimal IHC markers. Their differentiation from EOCs and other metastatic carcinomas is imperative in view of significant treatment implications.
Keywords: Calretinin, D2–40, peritoneal malignancy, peritoneal mesothelioma, rare gynecologic malignancies
|How to cite this URL:|
Karmarkar S, Rekhi B, Deodhar KK, Menon S. Histopathological and immunohistochemical features of 14 peritoneal mesotheliomas with clinical outcomes and recent updates. J Can Res Ther [Epub ahead of print] [cited 2022 Jul 3]. Available from: https://www.cancerjournal.net/preprintarticle.asp?id=330542
| > Introduction|| |
Malignant peritoneal mesotheliomas (MPMs) are rare and at times diagnostically challenging neoplasms, arising from the serosal membranes of the peritoneum. These tumors are lethal and mostly associated with poor prognosis and a survival rate of less than 1 year, postdiagnosis. One of the significant reasons for a poor survival rate is delayed diagnosis, leading to delayed treatment. The reasons for a delayed diagnosis in such cases include the rarity of these tumors; a lower index of suspicion; atypical clinical presentations; as well as their overlapping clinicopathological features; especially with epithelial ovarian carcinomas (EOCs) and primary peritoneal carcinomas (PPCs).
Diagnosis of MPMs and their differentiation from their mimics can be challenging, and a definitive diagnosis is possible by meticulous histopathological examination, supported by immunohistochemical (IHC) results, in an appropriate clinicoradiological context.
More recently, with the advent of hyperthermic intraperitoneal chemotherapy (HIPEC) to treat the residual disease, in adjunct to aggressive debulking surgery, the survival trend in these patients has considerably improved. Therefore, a timely and specific diagnosis of these tumors is crucial, in view of its significant therapeutic implications.
Till date, there has been no reported series with a sizable number of MPMs, confirmed by histopathological and IHC results, from our country, to the best of our knowledge.
The present study was undertaken with an aim to analyze clinicopathological features, including the IHC profile of MPMs, diagnosed at our institute.
| > Materials And Methods|| |
This was a descriptive study that included retrospectively diagnosed cases of MPMs at our institution, between January 2008 and May 2019 (11 years). Seventeen diagnosed cases of MPM were identified from the departmental archives. Fourteen cases were included as slides and paraffin blocks of three cases could not be retrieved. All the cases were reviewed by B.R. with S.K.
The diagnostic criteria included clinical features, including a mass lesion, significantly involving the peritoneum, and histopathologically prominent mesothelial proliferation, displaying invasion. The diagnosis was reinforced with immunohistochemical markers of mesothelial differentiation (calretinin, D2–40, HBME1, and CK5/6), with varying combinations, in all the cases. There was a single case of well-differentiated mesothelioma, lacking stromal invasion.
Various clinical parameters, such as age of the patient; symptomatology, tumor marker levels; differential diagnoses at presentation; cytological features; histopathological, IHC features; and treatment details, along with clinical outcomes, were recorded from the case files and electronic medical records of our Institution.
IHC was performed on formalin-fixed/paraffin-embedded tissue sections by immunoperoxidase method using a MACH2 Universal HRP-Polymer detection kit. IHC antibody markers tested and found to be positive in various cases are enlisted in [Table 1].
|Table 1: List of antibody immunohistochemical markers found to be positive in cases of the present study|
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Histopathological sections in all cases along with cytological smears (wherever available) were critically reviewed by two authors. In addition, details pertaining to pretreatment (chemotherapy) along with radiological features were also noted.
Events were recorded in the form of recurrences, metastasis, and death. Chi-square or Fisher's exact test was used for categorical variables. Kaplan–Meier analysis was used to estimate survival, and the log-rank test was used to assess differences by groups. Various clinicopathological parameters were correlated with disease-free survival (DFS) and overall survival (OS). Statistical significance was considered for P ≤ 0.05.
| > Results|| |
Fourteen tumors occurring in female patients were included. Average age of the patients was 50 years, ranging from 23 to 65 years. Most patients (10/14; 71.4%) were postmenopausal. History of an active exposure to asbestos could not be elicited in any of these patients.
Clinical details including symptomatology (in certain cases) were available in 14 cases. Most commonly observed symptoms were abdominal distension in seven (77.8%) cases and abdominal pain in four (28.6%) cases, as a result of ascites, along with loss of appetite in three (21.4%) cases. A single patient presented with an abdominal mass, accompanied with ascitis. Pretreatment CA-125 levels were available in five cases and ranged from 41.6 to 127 U/ml.
Detailed radiologic findings were available in nine cases (64.3%), all of which revealed ascitis and omental nodularity with fat stranding. Clinicoradiological context of a peritoneal tumor was known in all the cases. Ovarian enlargement was observed in three cases (unilateral in two cases and bilateral in a single case), out of which microscopic involvement by the tumor was seen in a single case with bilateral ovarian involvement.
Cytopathological diagnosis was available in 4/14 (28.5%) cases, including three cases, which were available for review. All three cases, including two cases, which were initially misdiagnosed as adenocarcinomas, on review, showed features indicative of mesothelioma. These were “mulberry-like” clusters of enlarged mesothelial cells with enlarged nuclei, prominent nucleoli, and abundant cytoplasm; “blebbing” of cell membranes; “cell-within-cell” arrangement; and intracytoplasmic vacuolation [Figure 1]a. A single case (case 13) on a cell block preparation was diagnosed as atypical mesothelial proliferation with support of immunostains.
|Figure 1: (a) Ascitic fluid smears showing singly scattered and “mulberry-like” clusters of mesothelial cells with enlarged nuclei (Giemsa, ×400). (b) Malignant peritoneal mesothelioma, epithelioid type, comprising infiltrating epithelioid-type atypical mesothelial cells (H and E, ×200)|
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Gross findings were available in three (21.4%) cases, all of which showed multiple peritoneal nodules. There was a large pelvic mass measuring 6 cm, in a single case.
Based on their morphologic features, 14 MPMs were further classified as epithelioid (11; 78.6%), biphasic (2 cases; 14.3%), and well-differentiated (single case) subtypes. We did not identify any case of sarcomatoid MPM.
Among 11 cases of epithelioid MPMs, varied histopathological growth patterns could be elicited in eight cases (72.7%), of which tubulopapillary pattern was the most common pattern (6/8; 72.7%) followed by a solid and a deciduoid pattern, observed in a single case each, respectively. Tissue invasion was seen in all cases, including stromal invasion in six cases and adipose tissue invasion in two cases. Tumors with a tubulopapillary pattern displayed mild-to-moderate nuclear atypia with mitosis ranging from 0 to 2/10 high power fields (hpf). The tumor with solid pattern displayed moderate nuclear atypia and rare mitotic figures (less than 1/10 hpf), while tumor with deciduoid pattern displayed moderate-to-severe nuclear atypia, with mitotic figures ranging from 3 to 4/10 hpf.
Two (14%) tumors displayed biphasic appearance, in the form of tumor cells with epithelioid (relatively bland, low cuboidal type) and sarcomatoid (spindly to polygonal shaped cells) differentiation, the latter amounting to more than 10% of the tumor. These tumors displayed mitotic figures, ranging from 4 to 5/10 hpf, along with interspersed areas of necrosis.
A single (7.1%) case of well-differentiated MPM was noted, which displayed atypical epithelial proliferation with a predominant papillary pattern and focal myxoid stroma, lacking tumor invasion. There was minimal nuclear atypia with no mitotic figures or necrosis.
IHC staining was performed in all 14/14 (100%) cases. Most frequently performed IHC antibody markers and their respective positive expression in various cases were calretinin (13/13; 100%), WT1 (9/10; 90%), cytokeratin (CK) 7 (7/8; 87.5%), PAX8 (1/8; 12.5%), desmin (1/6; 16.7%), p53 (3/6; 50%), mesothelin (HBME1) (5/5; 100%), and podoplanin (D2–40) (2/5; 40%). Other less frequently tested IHC markers were epithelial membrane antigen (EMA) (2/5), CK5/6 (1/1), CK7 (7/8)(87.5%), CK19 (1/1), CK20 (0/4), CDX2 (0/3), BerEP4 (0/3), CA-125 (1/1), estrogen receptor (0/4), progesterone receptor (0/1), TTF1 (0/1), Hepar1 (0/1), MIC2 (0/1), synaptophysin (0/1), CD15 (0/1), CD20 (0/1), beta-catenin (0/1), CD117/C-kit (0/1), inhibin (0/1), and Ki-67/MIB (5%–15%, in 6 tumors).
Among two cases of biphasic MPMs, tumor cells were diffusely and strongly positive for calretinin however were focally and weakly positive for WT1, compared to epithelioid MPMs.
A single case of well-differentiated mesothelioma displayed diffuse and strong positivity for mesothelin (HBME1) and focal positivity for EMA and p53 while negativity for PAX8 and desmin [Figure 1]b and [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7].
|Figure 2: (a) Ascitic fluid cell block preparation showing atypical mesothelial cells with enlarged nuclei, prominent nucleoli, intracytoplasmic vacuolation, “cell-within-cell” arrangement along with “blebbing” of cell membranes (H and E, ×400). (b) Tumor cells showing diffuse and strong membranous positivity for mesothelin (HBME1) (DAB, ×400). (c) Staining for desmin highlighting an occasional reactive mesothelial cell. Tumor cells show complete negative staining (DAB, ×400). (d) Tumor cells showing distinct, focal nuclear positivity for p53 (DAB, ×400)|
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|Figure 3: (a) Malignant peritoneal mesothelioma; epithelioid type with a tubulopapillary pattern (H and E, ×400). (b) Stain for mucicarmine highlighting extracellular mucin (Mucicarmine, ×400). (c) Tumor cells showing diffuse and strong, cytoplasmic membranous positivity for CK7 (DAB, ×100). (d) Tumor cells showing diffuse and strong, nuclear, and cytoplasmic positivity for calretinin (DAB, ×400)|
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|Figure 4: (a) Malignant peritoneal mesothelioma, epithelioid type with focal solid pattern (H and E, ×400). (b) Focal glandular pattern of tumor cells (H and E, ×400). (c) Tumor cells showing diffuse and strong nuclear and cytoplasmic positivity for calretinin (DAB, ×400). (d) Tumor cells showing focal, but strong positivity for podoplanin (D2–40) (DAB, ×200). (e) Tumor cells show focal and weak cytoplasmic (dot-like) positivity for desmin (DAB, ×200)|
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|Figure 5: (a) Malignant peritoneal mesothelioma, epithelioid type with a deciduoid pattern, comprising cells in sheets with trabecular patterns (H and E, ×200). (b) Higher magnification showing tumor cells with abundant eosinophilic cytoplasm and marked nuclear pleomorphism. (c) Tumor cells showing diffuse, strong nuclear and cytoplasmic positivity for calretinin (DAB, ×200). (d) Diffuse and strong, membranous positivity for podoplanin (D2–40) (DAB, ×200). (e) Focal and weak nuclear positivity for WT1 (DAB, ×200). (f) Diffuse and strong positivity for p53 (mutation type) (DAB, ×400)|
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|Figure 6: (a) Malignant peritoneal mesothelioma; biphasic type. Areas with spindle cell proliferation (H and E, ×400). (b) Areas with epithelioid differentiation (H and E, ×400). (c) Tumor cells showing diffuse and strong, membranous AE1/AE3 staining in the areas with epithelioid differentiation (DAB, ×400). (d) Diffuse, strong nuclear and cytoplasmic positivity for calretinin (DAB, ×400). (e) Focal and weak nuclear positivity for WT1 (DAB, ×200)|
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|Figure 7: (a) Well-differentiated mesothelioma. Tubulopapillary pattern (H and E, ×100). (b) Higher magnification shows papillae lined by tumor cells showing mild nuclear atypia (H and E, ×200)|
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Overall, calretinin, mesothelin (HBME1) and podoplanin (D2–40) were highly sensitive (100%, 100%, and 60%, respectively) and fairly specific (85.7%, 100%, and 100%, respectively) markers for MPMs.
Treatment details were available in 12/14 (85.7%) cases. Various treatment modalities were offered including chemotherapy (5/12; 41.7%), neoadjuvant chemotherapy, followed by interval debulking surgery and HIPEC (3/12; 25%), and tamoxifen (2/12; 16.7%). Neoadjuvant chemotherapy followed by interval debulking surgery and adjuvant chemotherapy and palliative chemotherapy were also offered in a single patient each, respectively.
Clinical details regarding follow-up were available in 10/14 (71.4%) cases. The follow-up duration ranged from a minimum of 1–78 months (median = 24 months). During follow-up, a single patient developed tumor recurrence (preceding metastasis) and two patients developed metastatic lesions to the liver, following which both were offered palliative chemotherapy.
Finally, out of the 14 patients, five (35.7%) patients were alive-with-disease (duration ranging from 16 to 78 months) and five (35.7%) patients died-of-disease (duration ranging from 1 to 25 months). Remaining 4 (28.6%) patients were lost to follow-up [Table 2].
|Table 2: Clinicopathological features of 14 cases of peritoneal mesotheliomas|
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Considering the number of patients alive (with or without disease) exceeded more than 50% at the longest time point, median OS could not be obtained. The 3-year DFS and OS rates were 25.7% and 54%, respectively.
On correlating various clinicopathological variables, including presence of distant metastasis, histopathological subtypes of the tumor, nuclear grade, depth of invasion, presence of necrosis, presence of mitosis, and status of patients treated with HIPEC, with OS and DFS, no statistically significant association was obtained due to low power estimates, for these rather rare group of tumors.
| > Discussion|| |
MPMs are much less common than their pleural counterparts. There is limited documentation on their clinicopathological features, including less than 10 cases of MPM reported from our country, in four different studies, respectively.,,,, The present study constitutes the first comprehensive study on morphological spectrum and IHC features with clinical outcomes, of 14 MPMs. In terms of etiology, asbestos exposure is considered as one of possible reasons for occurrence of this tumor. In the present study, history of asbestos exposure could not be elicited in any of the cases.
Most patients in the present study were postmenopausal, with an average age of 50 years presenting with abdominal distension, as a result of ascites, diffuse peritoneal nodularity, abdominal pain, and loss of appetite, as similarly reported in previous studies.,,
Ovaries were unremarkable in most of these cases, on radiologic imaging. In three cases, ovarian enlargement (unilateral or bilateral) was observed during preoperative radioimaging, simulating a primary ovarian neoplasm. Among those cases, a single case showed minimal ovarian involvement by the tumor. Similar findings were reported by Clement et al. and Hancock et al., in two different studies, respectively.
Microscopically, the most commonly observed morphological subtype in our study was epithelioid, in 78.6% tumors, followed by biphasic in 14% and a single case of a well-differentiated type of MPM.
Epithelioid MPMs predominantly displayed a tubulopapillary pattern (75%), followed by a solid and deciduoid pattern in a single case each, respectively. Baker et al. studied the clinicopathological spectrum of 75 cases of MPMs in women, emphasizing upon the histomorphological patterns. Among the 70 (93.3%) cases of epithelioid MPMs in their study, most tumors displayed a tubular pattern, frequently accompanied by a papillary or solid pattern or a combination of all three, as observed in our study. Similar to the present study, wherein we identified a single case of an epithelioid MPM with a deciduoid pattern, two tumors with a deciduoid pattern were identified in that study. This rare pattern is characterized by tumor cells arranged in solid sheets, comprising cells with abundant eosinophilic cytoplasm, high-grade nuclei, and more frequent mitotic figures., Histologic mimics of a deciduoid mesothelioma include carcinoma and deciduoid variant of a germ cell tumor, which can be differentiated with certain IHC stains.
We observed two cases of biphasic MPM, comprising epithelioid and sarcomatoid differentiation. Individual tumor cells in the epithelioid areas displayed mild nuclear pleomorphism and papillary arrangement, while those in the sarcomatoid areas displayed mild-to-moderate nuclear pleomorphism, conspicuous intranuclear grooving, infrequent mitotic figures, and interspersed areas of necrosis. Similar microscopic features were reported in previous studies.,,
Well-differentiated mesothelioma constitutes a rare subtype of mesothelial neoplasm with an uncertain malignant potential. There is limited information available regarding its biological behavior and rare cases of these tumors giving rise to malignant mesotheliomas have been reported in the literature. We designated a single tumor in this study as well differentiated on the basis of histopathological features, including an orderly papillary architecture, relatively bland mesothelial cells, lack of mitotic figures, and tumor invasion.,
Several investigators have documented the utility of various IHC markers in the diagnosis of mesotheliomas, including its distinction from an EOC and a PPC, which constitute its differential diagnoses. Among various IHC markers of mesothelial differentiation, calretinin is one of the most widely tested markers. Ordóñez observed strong calretinin positivity in all 35/35 (100%) cases of MPMs. More recently, Kawai et al., Barnetson et al., Comin et al., and Tandon et al. in four different studies observed calretinin positivity in 91%, 85%, 100%, and 100% cases of mesotheliomas, respectively. Likewise, in our study, calretinin was one of the most frequently tested IHC markers, which was diffusely and strongly expressed in all 14/14 (100%) cases of MPM. Calretinin can be expressed in some EOCs. However, in view of its consistently strong immunoexpression in MPMs, negative staining for calretinin may be considered against a diagnosis of MPMs.
Mesothelin (HBME1) has not been extensively tested in mesotheliomas. There are variable results reported in the literature, with respect to its sensitivity and specificity. In one of the largest studies comprising 244 cases of MPMs, Tandon et al. observed mesothelin positivity in 100% of cases. We observed diffuse and strong membranous positivity in 5/5 (100%) cases, wherein it was tested. In two different studies, Ordóñez and Barnetson et al. observed a relatively higher rate of HBME1 immunopositivity in PPCs (100%, 89%), as compared to mesotheliomas (84%, 65%), therefore showing its limited specificity.
In addition, we noted diffuse and strong membranous positivity for podoplanin (D2–40) in 2/5 (40%) cases. The frequency of D2–40 positivity has been variably reported in earlier studies, wherein the authors reported its sensitivity ranging from 60% to 100%, in different studies.,, While calretinin and D2–40 constitute as markers of mesothelial differentiation, PAX8 is a IHC marker of Müllerian differentiation, therefore more frequently expressed in EOCs, including a sensitivity ranging from 92% to 100% and specificity of approximately 95%.,, It is rarely expressed in cases of mesotheliomas and therefore is a widely accepted marker in distinguishing the two tumors. We observed focal and weak PAX8 positivity in a single case of MPM, out of the eight cases, wherein it was tested. That particular tumor was diffusely positive for calretinin, reinforcing a diagnosis of MPM.
WT1 is invariably positive in serous carcinomas of the ovary and peritoneum (93%–100%),, and can also be positively expressed in mesotheliomas. We observed WT1 positivity in 9/10 (90%) cases of MPMs. With a sensitivity of 90% and a specificity of only 13.3% in cases of MPMs, this marker is not very useful in differentiating MPMs from serous carcinomas. However, we also observed that the positivity for WT1 was focal and weak in biphasic MPMs as compared to epithelioid MPMs.
CK5/6 is a considerably sensitive (53%–100%) marker in cases of mesotheliomas. We observed strong cytoplasmic CK5/6 positivity in 100% (4/4) cases of MPMs, where these markers were tested. However, due to lack of specificity, this marker is of limited use in differentiating the two tumors.
In this way, calretinin, D2–40, and PAX8 constitute an optimum panel for differentiating an MPM from EOC and PPC. The current recommendations are to use two mesothelial and two carcinoma markers to resolve this diagnostic scenario.,,
At times, there can be a challenge in the distinction of MPM from reactive mesothelial hyperplasia (RMH). In this study, markers such as desmin (complete negative staining in MPMs as opposed to positive staining in RMH) and EMA (complete and strong membranous staining in MPMs as opposed to weak and focal membranous staining in RMH) were helpful in resolving this diagnostic dilemma, as previously reported.,
More recently, two newer biomarkers, BRCA-associated protein 1 (BAP1) and p16INK4a (CDKN2A), have shown unprecedented specificity (100%) in separating reactive and malignant mesothelial proliferations.,
In a study by Cigognetti et al. in 2015, 79/79 (100%) benign mesothelial tumors were found to be immunopositive for BAP1, whereas 139/212 (66%) mesotheliomas showed BAP1 negativity. Furthermore, BAP1 immunostain has been found to be useful in differentiating MPMs from its potential mimickers, including ovarian carcinomas with a sensitivity and specificity of 100% and 70%, respectively. Following this, Chapel et al. observed similar findings in a recent study. It is noteworthy that irrespective of the choice of immunostains, as per availability in a laboratory, it is imperative to interpret immune results in a clinicoradiological context in all cases.
Lately, homozygous deletion of p16 tested by fluorescence in situ hybridization (FISH) technique is more commonly reported in pleural mesotheliomas as compared to MPMs. Despite its 100% specificity, its limited sensitivity, ranging from 14% to 51%, in cases of MPMs and the requirement to use FISH technique, instead of IHC staining, are some of the deterrent factors for inclusion of this relatively esoteric test in most laboratories, including ours. Nonetheless, the limited sensitivity of p16 test can be improved to some extent by running both, FISH and IHC staining.
Therapeutically, various treatment options are available for MPMs. During recent years, as a result of treatment with HIPEC, to control residual disease, the median survival has increased to nearly 5 years. In the present study, the types of chemotherapy regimens varied and 3/12 (25%) patients were treated with neoadjuvant chemotherapy (NACT), followed by debulking surgery and subsequently HIPEC. While NACT might play a role in a more advanced disease, its efficacy is still being investigated and the present recommendation for treating a MPM is by debulking surgery, followed by HIPEC.
More recently, it has been observed that MPMs associated with germline BAP1 mutations occur more frequently in women, at a younger age (<50 years) and without a history of asbestos exposure. Early identification of such patients may influence subsequent therapeutic choices leading to a better prognosis. Moreover, genetic counseling of their susceptible family members can be lifesaving.
The estimated rate of OS over duration of 5 years, in the present study, was 54%, which was comparable to the results in a study by Faig et al. (52%). Although we could not obtain statistically significant results on co-relating various clinicopathological variables with survival, we observed an improved survival trend in patients with epithelioid type of MPMs; tumors with a low nuclear grade, low mitotic count, and absence of necrosis, as observed in previous studies.,
| > Conclusion|| |
The present study constitutes one of the largest documentation on MPMs in females, from our country. MPMs have a wide histopathological spectrum, including several tumor growth patterns. In view of the rarity of these tumors, there is a considerable challenge and a lower index of suspicion for MPMs, resulting in their underdiagnoses, at times. IHC is essential for resolving these differential diagnoses. It is recommended to utilize more specific and sensitive IHC markers. Distinction of MPMs from EOCs and other metastatic carcinomas is imperative, in view of significant treatment implications.
| > Acknowledgments|| |
We would like to acknowledge Immunohistochemistry Laboratory of our Department.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| > References|| |
Manzini VP, Recchia L, Cafferata M, Porta C, Siena S, Giannetta L, et al
. Malignant peritoneal mesothelioma: A multicenter study on 81 cases. Ann Oncol 2010;21:348-53.
García-Fadrique A, Mehta A, Mohamed F, Dayal S, Cecil T, Moran BJ. Clinical presentation, diagnosis, classification and management of peritoneal mesothelioma: A review. J Gastrointest Oncol 2017;8:915-24.
Taşkın S, Gümüş Y, Kiremitçi S, Kahraman K, Sertçelik A, Ortaç F. Malignant peritoneal mesothelioma presented as peritoneal adenocarcinoma or primary ovarian cancer: Case series and review of the clinical and immunohistochemical features. Int J Clin Exp Pathol 2012;5:472-8.
Deraco M, Nonaka D, Baratti D, Casali P, Rosai J, Younan R, et al
. Prognostic analysis of clinicopathologic factors in 49 patients with diffuse malignant peritoneal mesothelioma treated with cytoreductive surgery and intraperitoneal hyperthermic perfusion. Ann Surg Oncol 2006;13:229-37.
Gilks CB, Oliva E, Solomon DA. Mesothelioma. In: World Health Organization (WHO) Classification of Tumours Editorial Board, editors. World Health Organization Classification of Tumours. 5th
ed. Female Genital Tumours. Lyon, France: IARC Press; 2020. p. 181-3.
Daya D, McCaughey WT. Well-differentiated papillary mesothelioma of the peritoneum. A clinicopathologic study of 22 cases. Cancer 1990;65:292-6.
Baker PM, Clement PB, Young RH. Malignant peritoneal mesothelioma in women: A study of 75 cases with emphasis on their morphologic spectrum and differential diagnosis. Am J Clin Pathol 2005;123:724-37.
Rekhi B, Pathuthara S, Ajit D, Kane SV. “Signet-ring” cells – A caveat in the diagnosis of a diffuse peritoneal mesothelioma occurring in a lady presenting with recurrent ascites: an unusual case report. Diagn Cytopathol 2010;38:435-9.
Arora SK, Srinivasan R, Nijhawan R, Bansal D, Menon P. Malignant biphasic peritoneal mesothelioma in a child: Fine-needle aspiration cytology, histopathology, and immunohistochemical features along with review of literature. Diagn Cytopathol 2012;40:1112-5.
Kapoor R, Kuttikat PG, Vaiphei K, Rai B, Patel FD. A case report of peritoneal malignant mesothelioma presenting as primary ovarian mass. J Cancer Res Ther 2015;11:654.
Hui M, Uppin SG, Bhaskar K, Kumar NN, Paramjyothi GK. Malignant mesothelioma: A histomorphological and immunohistochemical study of 24 cases from a tertiary care hospital in Southern India. Indian J Cancer 2018;55:190-5.
] [Full text]
Eltabbakh GH, Piver MS, Hempling RE, Recio FO, Intengen ME. Clinical picture, response to therapy, and survival of women with diffuse malignant peritoneal mesothelioma. J Surg Oncol 1999;70:6-12.
Clement PB, Young RH, Scully RE. Malignant mesotheliomas presenting as ovarian masses. A report of nine cases, including two primary ovarian mesotheliomas. Am J Surg Pathol 1996;20:1067-80.
Hancock KL, Clinton CM, Dinkelspiel HE, Saab J, Schneider B, Caputo TA. A case of mesothelioma masquerading pre-operatively as ovarian cancer and brief review of the literature. Gynecol Oncol Rep 2016;17:26-8.
Ordóñez NG. Deciduoid mesothelioma: Report of 21 cases with review of the literature. Mod Pathol 2012;25:1481-95.
Komaki T, Urata H, Mori K, Iwashita A, Ikeda K, Haraoka S. A rare case of biphasic malignant peritoneal mesothelioma with refractory ascites. Intern Med 2017;56:861-4.
Kohno M, Maruyama R, Kitagawa D, Sugimachi K, Kinjo M, Higashi H. Localized biphasic type malignant mesothelioma arising in the peritoneum: Report of a case. Thorac Cancer 2014;5:74-7.
Malpica A, Sant'Ambrogio S, Deavers MT, Silva EG. Well-differentiated papillary mesothelioma of the female peritoneum: A clinicopathologic study of 26 cases. Am J Surg Pathol 2012;36:117-27.
Ordóñez NG. Role of immunohistochemistry in distinguishing epithelial peritoneal mesotheliomas from peritoneal and ovarian serous carcinomas. Am J Surg Pathol 1998;22:1203-14.
Kawai T, Tominaga S, Hiroi S, Ogata S, Nakanishi K, Kawahara K, et al
. Peritoneal malignant mesothelioma (PMM), and primary peritoneal serous carcinoma (PPSC) and reactive mesothelial hyperplasia (RMH) of the peritoneum. Immunohistochemical and fluorescence in situ
hybridisation (FISH) analyses. J Clin Pathol 2016;69:706-12.
Barnetson RJ, Burnett RA, Downie I, Harper CM, Roberts F. Immunohistochemical analysis of peritoneal mesothelioma and primary and secondary serous carcinoma of the peritoneum: Antibodies to estrogen and progesterone receptors are useful. Am J Clin Pathol 2006;125:67-76.
Comin CE, Saieva C, Messerini L. h-caldesmon, calretinin, estrogen receptor, and Ber-EP4: A useful combination of immunohistochemical markers for differentiating epithelioid peritoneal mesothelioma from serous papillary carcinoma of the ovary. Am J Surg Pathol 2007;31:1139-48.
Tandon RT, Jimenez-Cortez Y, Taub R, Borczuk AC. Immunohistochemistry in peritoneal mesothelioma: A single-center experience of 244 cases. Arch Pathol Lab Med 2018;142:236-42.
Ordóñez NG. Value of mesothelin immunostaining in the diagnosis of mesothelioma. Mod Pathol 2003;16:192-7.
Chu AY, Litzky LA, Pasha TL, Acs G, Zhang PJ. Utility of D2-40, a novel mesothelial marker, in the diagnosis of malignant mesothelioma. Mod Pathol 2005;18:105-10.
Ordóñez NG. D2-40 and podoplanin are highly specific and sensitive immunohistochemical markers of epithelioid malignant mesothelioma. Hum Pathol 2005;36:372-80.
Chai HJ, Ren Q, Fan Q, Ye L, Du GY, Du HW, et al
. PAX8 is a potential marker for the diagnosis of primary epithelial ovarian cancer. Oncol Lett 2017;14:5871-5.
Laury AR, Perets R, Piao H, Krane JF, Barletta JA, French C, et al
. A comprehensive analysis of PAX8 expression in human epithelial tumors. Int J Gynecol Pathol 2017;36:101-6.
Laury AR, Hornick JL, Perets R, Krane JF, Corson J, Drapkin R, et al
. PAX8 reliably distinguishes ovarian serous tumors from malignant mesothelioma. Am J Surg Pathol 2010;34:627-35.
Ordóñez NG. The immunohistochemical diagnosis of mesothelioma: A comparative study of epithelioid mesothelioma and lung adenocarcinoma. Am J Surg Pathol 2003;27:1031-51.
Oates J, Edwards C. HBME-1, MOC-31, WT1 and calretinin: An assessment of recently described markers for mesothelioma and adenocarcinoma. Histopathology 2000;36:341-7.
Foster MR, Johnson JE, Olson SJ, Allred DC. Immunohistochemical analysis of nuclear versus cytoplasmic staining of WT1 in malignant mesotheliomas and primary pulmonary adenocarcinomas. Arch Pathol Lab Med 2001;125:1316-20.
Husain AN, Colby TV, Ordóñez NG, Allen TC, Attanoos RL, Beasley MB, et al
. Guidelines for pathologic diagnosis of malignant mesothelioma 2017 update of the consensus statement from the international mesothelioma interest group. Arch Pathol Lab Med 2018;142:89-108.
Robinson BW, Lake RA. Advances in malignant mesothelioma. N Engl J Med 2005;353:1591-603.
Lee M, Alexander HR, Burke A. Diffuse mesothelioma of the peritoneum: A pathological study of 64 tumours treated with cytoreductive therapy. Pathology 2013;45:464-73.
Wolanski KD, Whitaker D, Shilkin KB, Henderson DW. The use of epithelial membrane antigen and silver-stained nucleolar organizer regions testing in the differential diagnosis of mesothelioma from benign reactive mesothelioses. Cancer 1998;82:583-90.
King J, Thatcher N, Pickering C, Hasleton P. Sensitivity and specificity of immunohistochemical antibodies used to distinguish between benign and malignant pleural disease: A systematic review of published reports. Histopathology 2006;49:561-8.
Churg A, Sheffield BS, Galateau-Salle F. New markers for separating benign from malignant mesothelial proliferations: Are we there yet? Arch Pathol Lab Med 2016;140:318-21.
Cigognetti M, Lonardi S, Fisogni S, Balzarini P, Pellegrini V, Tironi A, et al
. BAP1 (BRCA1-associated protein 1) is a highly specific marker for differentiating mesothelioma from reactive mesothelial proliferations. Mod Pathol 2015;28:1043-57.
Chapel DB, Schulte JJ, Husain AN, Krausz T. Application of immunohistochemistry in diagnosis and management of malignant mesothelioma. Transl Lung Cancer Res 2020;9:S3-27.
Kittaneh M, Berkelhammer C. Detecting germline BAP1 mutations in patients with peritoneal mesothelioma: Benefits to patient and family members. J Transl Med 2018;16:194.
Faig J, Howard S, Levine EA, Casselman G, Hesdorffer M, Ohar JA. Changing pattern in malignant mesothelioma survival. Transl Oncol 2015;8:35-9.
Liu S, Staats P, Lee M, Alexander HR, Burke AP. Diffuse mesothelioma of the peritoneum: Correlation between histological and clinical parameters and survival in 73 patients. Pathology 2014;46:604-9.
Pillai K, Pourgholami MH, Chua TC, Morris DL. Prognostic significance of Ki67 expression in malignant peritoneal mesothelioma. Am J Clin Oncol 2015;38:388-94.
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7]
[Table 1], [Table 2]