Downloaded from http://jcp.bmj.com/ on December 1, 2014 - Published by group.bmj.com
PostScript
CORRESPONDENCE
Primary extranodal marginal zone B cell lymphoma of the uterus: a case study and review of the literature Extranodal non-Hodgkin’s lymphoma (NHL) within the female genital tract is unusual, accounting for 1.5% of extranodal NHL, mostly in the ovaries. Primary NHLs of the uterus and cervix are rare, comprising only 0.54%–0.64% of all extranodal NHLs, most occurring in the cervix.1 Marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) of the uterus is extremely rare, with only seven cases reported in the literature.2–8 We report a rare case of an extranodal marginal zone B cell lymphoma arising from the MALT tissue of the endometrium. A 77-year-old woman presented with utero-vaginal prolapse, urinary frequency
and nocturia; she had no B symptoms. Examination revealed a cystocoele and a cervical prolapse. There was no palpable lymphadenopathy or hepatosplenomegally and she underwent vaginal hysterectomy and pelvic floor repair. The uterus and cervix measured 8.3×2.6×2.2 cm. The endometrium was 0.2 cm thick and the myometrium 1.6 cm thick; both appeared normal. Microscopically, the endometrium and superficial myometrium contained a nodular infiltrate of monotonous, small to medium-sized, lymphoid cells (figure 1A). The cells had slightly irregular nuclei with inconspicuous nucleoli and pale eosinophilic cytoplasm and a proportion had clear cytoplasm, imparting a monocytoid appearance. Scattered lymphoid blasts and plasma cells were also present (figure 1B). The nodules focally infiltrated and destroyed the endometrial glands, producing lymphoepithelial lesions. The lymphoid cells expressed CD20, CD43, CD79a and BCL2 (representative image shown for CD20 in figure 1C). They were negative for CD5, CD10, CD23, Bcl-6 and cyclin D1. A smaller number of small reactive
T cells were also present. Staining with CD21 and CD23 highlighted follicular dendritic cell networks within the lymphoid nodules, consistent with colonised follicles (figure 1D). A diagnosis of extranodal marginal zone lymphoma of MALT of the endometrium was made, supported by the finding of monoclonal B cell expansion by PCR (figure 2). Full blood count, biochemical profile and lactate dehydrogenase were within normal limits. A staging CT scan showed no evidence of extra-uterine spread (Stage IAE) and the patient was managed conservatively with follow-up only. Extranodal marginal zone B cell lymphomas of the uterus are extremely rare with only seven cases previously reported in the literature (table 1, including the current case).2–8 The mean age of presentation was 65 years (range 43–81). Three presented with abnormal vaginal bleeding, one with pelvic pressure effect causing dysuria and three were incidental findings. None of the seven cases or our case reported B symptoms, consistent with the indolent nature of the disease.
Figure 1 Histology of endometrial tissue showing (A) well demarcated nodular proliferations of lymphoid cells (H&E staining, original magnification ×40), (B) small to medium-sized lymphoid cells with lymphoepithelial lesions (H&E staining, ×400), (C) immunohistochemistry highlighting CD20 positive lymphocytes within the lymphoma nodules, ×100, (D) immunohistochemistry demonstrating CD21 positive follicular dendritic cell networks within the lymphoid nodules. J Clin Pathol April 2014 Vol 67 No 4
375
Downloaded from http://jcp.bmj.com/ on December 1, 2014 - Published by group.bmj.com
PostScript
Figure 2 Polyacrylamide gel (6%) of IgH FR2/JH PCR products. Lane 1, no template control; 2, positive control B cell lymphoma showing a dominant band; 3 and 4, test case in duplicate showing evidence of monoclonal B cell expansion (two reproducible dominant bands). Extranodal marginal zone lymphoma shows somatic hypermutation of the variable regions, in keeping with postgerminal
centre memory B cell derivation. There are three, mutually exclusive, specific chromosomal translocations described in
MALT lymphomas, namely, t(11;18)(q21; q21), t(1;14)( p22;q32) and t(14;18)(q32; q21), with variable frequency at different sites. Trisomies of chromosomes 3, 12 and 18 have also been reported in MALT lymphomas. None were found in four of the previous cases assessed for translocations (table 1); translocations were not assessed in the present case. Histology was reported in six of the previous cases; in three, lymphoma was restricted to the endometrium and three also showed myometrial involvement. The histological differential diagnosis of extranodal marginal zone lymphomas of the uterus includes other haematological malignancies, endometrial stromal sarcoma and florid benign reactive lymphoid proliferations seen in inflammatory conditions such as follicular endometritis. The present case was distinguished from these by its morphological and immunohistochemical characteristics (figure 1) and presence of monoclonal B cell expansion (figure 2). Extra nodal marginal zone lymphomas typically have an indolent course, with a 5-year survival rate of 94%.1 Although six of the seven previously reported cases had short-term follow-up (7 months to 2 years), none had progression or recurrence. Primary lymphoma of the uterus is rare and primary extranodal marginal zone lymphoma of the uterus, extremely rare. We present a case with an incidental finding of extranodal marginal zone lymphoma of
Table 1 Summary of clinical, histological, immunohistochemical and staging data for reported cases of extranodal marginal zone B cell lymphoma of the uterus Case no.
Age (years)
Presentation
Site
Tumour cells Positive IHC
Tumour cells Negative IHC
Translocations
Stage
Reference
1
81
Incidental at CT scan
Polyp and stalk
CD20, CD79a, IRTA1, Bcl-6 (faint) CD79a, CD20, Mib-1
CD10
Not assessed
IE
2
2
61
Endometrium only
3
52
Incidental posthysterectomy for prolapse Menorrhagia
CD5, CD23, Bcl-6, CD10
FISH assessment t(14;18)(q32; q21). None found
IE
3
Endometrium only
CD20
Not given
IVE
4
Endometrium, iliac nodes Endometrium, superficial myometrium Endometrium, deep myometrium, pelvic node Endometrium, superficial myometrium
Not given
Not given
Cytogenetic analysis showed 46XX karyotype Not assessed
4
43
Inter-menstrual bleeding
IIE
5
5
65
6
72
Postmenopausal bleeding Pelvic pressure with dysuria
CD20, Bcl-2
Cyclin D1, CD10, Bcl-6, CD5 Not given
Not assessed
IE
6
Southern blotting bcl-1 and bcl-2 rearrangements. None found
IIE
7
7
80
Incidental posthysterectomy for prolapse
CD20
CD5, CD10, BCL-6, IgD
IIE
8
Endometrium, superficial myometrium
CD79a, CD20, Bcl-2, CD43
CD5, CD23, CD10, Bcl-6 cyclin D1
FISH assessment t(1;14)(p22; q32), t(11;18)(q21;q21), t(14;18 (q32;q21). None found Not assessed
8
77
Incidental posthysterectomy for prolapse
IAE
Current case
Not given
IHC, immunohistochemistry.
376
J Clin Pathol April 2014 Vol 67 No 4
Downloaded from http://jcp.bmj.com/ on December 1, 2014 - Published by group.bmj.com
PostScript the endometrium, and a summary of all seven previously reported cases. Accurate histological interpretation is essential for distinguishing extranodal marginal zone lymphoma from reactive lymphoid aggregates and other B cell lymphomas to ensure optimal management. Anita J Merritt,1 Patrick Shenjere,2 Lia P Menasce,2 Fiona Reid,3 Tim Diss,4 Rhona J McVey,1 Richard J Byers1,5 1
Department of Histopathology, Manchester Royal Infirmary, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK 2 Department of Histopathology, The Christie NHS Foundation Trust, Manchester, UK 3 Department of Gynaecology, St Marys Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK 4 Department of Pathology, UCL-Advanced Diagnostics, University College London, London, UK 5 Institute of Cancer Sciences, The University of Manchester, Manchester, UK Correspondence to Dr Richard Byers, Department of Histopathology, Clinical Sciences Building One, Manchester Royal Infirmary, Oxford Road, Manchester M13 9WL, UK; [email protected] and [email protected] Contributors AJM wrote the manuscript. PS, LPM, RJMcV and RJB made the diagnosis and wrote the manuscript. FR provided clinical liaison and treated the patient. TD undertook scientific analysis detailed in the case report. Competing interests None. Patients Consent Obtained. Provenance and peer review Not commissioned; internally peer reviewed. To cite Merritt AJ, Shenjere P, Menasce L P, et al. J Clin Pathol 2014;67:375–377. Received 20 November 2013 Accepted 24 November 2013 Published Online First 18 December 2013 J Clin Pathol 2014;67:375–377. doi:10.1136/jclinpath-2013-202059
REFERENCES 1
2
3
4
5
6
Chorlton I, Karnei RF Jr, King FM, et al. Primary malignant reticuloendothelial disease involving the vagina, cervix, and corpus uteri. Obstet Gynecol 1974;44:735–48. Annibali O, Romeo AA, Agostinelli C, et al. A case of primary MALT lymphoma of the endometrium presenting as an asymptomatic polyp. Ann Hematol 2009;88:491–3. Heeren JHM, Croonen AM, Pijnenborg JMA. Primary extranodal marginal zone B-cell lymphoma of the female genital tract: a case report and literature review. Int J Gynecol Pathol 2008;27:243–6. Hamadani M, Kharfan-Dabaja M, Kamble R, et al. Marginal zone B-cell lymphoma of the uterus: a case report and review of the literature. J Okla State Med Assoc 2006;99:154–6. Frey NV, Svoboda J, Andreadis C, et al. Primary lymphomas of the cervix and uterus: the University of Pennsylvania’s experience and a review of the literature. Leuk Lymphoma 2006;47:1894–901. Iyengar P, Deodhare S. Primary extranodal marginal zone B-cell lymphoma of MALT type of the endometrium. Gynecol Oncol 2004;93:238–41.
J Clin Pathol April 2014 Vol 67 No 4
7
8
Ballesteros E, Osborne BM, Matsushima AY. CD5+ low-grade marginal zone B-cell lymphomas with localized presentation. Am J Surg Pathol 1998;22:201–7. Wright T, Rule S, Liu H, et al. Extranodal marginal zone lymphoma of the uterine corpus. Leuk Lymphoma 2012;53:1831–4.
Focal nodular hyperplasia-like lesion in a cirrhotic liver mimicking a cholangiocarcinoma INTRODUCTION Focal nodular hyperplasia (FNH) is a common benign liver lesion composed of nodules of proliferating hepatocytes, malformed vessels, and bile ductular proliferation. Classically, FNH has been reported in livers which are normal or near normal. Recently, however, FNH-like lesions have been reported in cirrhotic livers and, as such, FNH should be considered in the clinicopathologic differential diagnosis of hepatocellular carcinoma (HCC) and other nodular liver lesions.1–3 As most of these lesions are detected by imaging studies, it is useful to review the imaging characteristics of FNH. Classical FNH usually has typical imaging characteristics. On unenhanced scans, the lesion is homogenous and well defined and may be either hypo- or iso-dense. It shows bright enhancement on the early arterial phase before becoming iso-dense on the portal phase. The characteristic stellate central scar is hypo-dense on early arterial and portal phases before becoming hyperdense on delayed scans. This, however, is only seen in
PostScript
CORRESPONDENCE
Primary extranodal marginal zone B cell lymphoma of the uterus: a case study and review of the literature Extranodal non-Hodgkin’s lymphoma (NHL) within the female genital tract is unusual, accounting for 1.5% of extranodal NHL, mostly in the ovaries. Primary NHLs of the uterus and cervix are rare, comprising only 0.54%–0.64% of all extranodal NHLs, most occurring in the cervix.1 Marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) of the uterus is extremely rare, with only seven cases reported in the literature.2–8 We report a rare case of an extranodal marginal zone B cell lymphoma arising from the MALT tissue of the endometrium. A 77-year-old woman presented with utero-vaginal prolapse, urinary frequency
and nocturia; she had no B symptoms. Examination revealed a cystocoele and a cervical prolapse. There was no palpable lymphadenopathy or hepatosplenomegally and she underwent vaginal hysterectomy and pelvic floor repair. The uterus and cervix measured 8.3×2.6×2.2 cm. The endometrium was 0.2 cm thick and the myometrium 1.6 cm thick; both appeared normal. Microscopically, the endometrium and superficial myometrium contained a nodular infiltrate of monotonous, small to medium-sized, lymphoid cells (figure 1A). The cells had slightly irregular nuclei with inconspicuous nucleoli and pale eosinophilic cytoplasm and a proportion had clear cytoplasm, imparting a monocytoid appearance. Scattered lymphoid blasts and plasma cells were also present (figure 1B). The nodules focally infiltrated and destroyed the endometrial glands, producing lymphoepithelial lesions. The lymphoid cells expressed CD20, CD43, CD79a and BCL2 (representative image shown for CD20 in figure 1C). They were negative for CD5, CD10, CD23, Bcl-6 and cyclin D1. A smaller number of small reactive
T cells were also present. Staining with CD21 and CD23 highlighted follicular dendritic cell networks within the lymphoid nodules, consistent with colonised follicles (figure 1D). A diagnosis of extranodal marginal zone lymphoma of MALT of the endometrium was made, supported by the finding of monoclonal B cell expansion by PCR (figure 2). Full blood count, biochemical profile and lactate dehydrogenase were within normal limits. A staging CT scan showed no evidence of extra-uterine spread (Stage IAE) and the patient was managed conservatively with follow-up only. Extranodal marginal zone B cell lymphomas of the uterus are extremely rare with only seven cases previously reported in the literature (table 1, including the current case).2–8 The mean age of presentation was 65 years (range 43–81). Three presented with abnormal vaginal bleeding, one with pelvic pressure effect causing dysuria and three were incidental findings. None of the seven cases or our case reported B symptoms, consistent with the indolent nature of the disease.
Figure 1 Histology of endometrial tissue showing (A) well demarcated nodular proliferations of lymphoid cells (H&E staining, original magnification ×40), (B) small to medium-sized lymphoid cells with lymphoepithelial lesions (H&E staining, ×400), (C) immunohistochemistry highlighting CD20 positive lymphocytes within the lymphoma nodules, ×100, (D) immunohistochemistry demonstrating CD21 positive follicular dendritic cell networks within the lymphoid nodules. J Clin Pathol April 2014 Vol 67 No 4
375
Downloaded from http://jcp.bmj.com/ on December 1, 2014 - Published by group.bmj.com
PostScript
Figure 2 Polyacrylamide gel (6%) of IgH FR2/JH PCR products. Lane 1, no template control; 2, positive control B cell lymphoma showing a dominant band; 3 and 4, test case in duplicate showing evidence of monoclonal B cell expansion (two reproducible dominant bands). Extranodal marginal zone lymphoma shows somatic hypermutation of the variable regions, in keeping with postgerminal
centre memory B cell derivation. There are three, mutually exclusive, specific chromosomal translocations described in
MALT lymphomas, namely, t(11;18)(q21; q21), t(1;14)( p22;q32) and t(14;18)(q32; q21), with variable frequency at different sites. Trisomies of chromosomes 3, 12 and 18 have also been reported in MALT lymphomas. None were found in four of the previous cases assessed for translocations (table 1); translocations were not assessed in the present case. Histology was reported in six of the previous cases; in three, lymphoma was restricted to the endometrium and three also showed myometrial involvement. The histological differential diagnosis of extranodal marginal zone lymphomas of the uterus includes other haematological malignancies, endometrial stromal sarcoma and florid benign reactive lymphoid proliferations seen in inflammatory conditions such as follicular endometritis. The present case was distinguished from these by its morphological and immunohistochemical characteristics (figure 1) and presence of monoclonal B cell expansion (figure 2). Extra nodal marginal zone lymphomas typically have an indolent course, with a 5-year survival rate of 94%.1 Although six of the seven previously reported cases had short-term follow-up (7 months to 2 years), none had progression or recurrence. Primary lymphoma of the uterus is rare and primary extranodal marginal zone lymphoma of the uterus, extremely rare. We present a case with an incidental finding of extranodal marginal zone lymphoma of
Table 1 Summary of clinical, histological, immunohistochemical and staging data for reported cases of extranodal marginal zone B cell lymphoma of the uterus Case no.
Age (years)
Presentation
Site
Tumour cells Positive IHC
Tumour cells Negative IHC
Translocations
Stage
Reference
1
81
Incidental at CT scan
Polyp and stalk
CD20, CD79a, IRTA1, Bcl-6 (faint) CD79a, CD20, Mib-1
CD10
Not assessed
IE
2
2
61
Endometrium only
3
52
Incidental posthysterectomy for prolapse Menorrhagia
CD5, CD23, Bcl-6, CD10
FISH assessment t(14;18)(q32; q21). None found
IE
3
Endometrium only
CD20
Not given
IVE
4
Endometrium, iliac nodes Endometrium, superficial myometrium Endometrium, deep myometrium, pelvic node Endometrium, superficial myometrium
Not given
Not given
Cytogenetic analysis showed 46XX karyotype Not assessed
4
43
Inter-menstrual bleeding
IIE
5
5
65
6
72
Postmenopausal bleeding Pelvic pressure with dysuria
CD20, Bcl-2
Cyclin D1, CD10, Bcl-6, CD5 Not given
Not assessed
IE
6
Southern blotting bcl-1 and bcl-2 rearrangements. None found
IIE
7
7
80
Incidental posthysterectomy for prolapse
CD20
CD5, CD10, BCL-6, IgD
IIE
8
Endometrium, superficial myometrium
CD79a, CD20, Bcl-2, CD43
CD5, CD23, CD10, Bcl-6 cyclin D1
FISH assessment t(1;14)(p22; q32), t(11;18)(q21;q21), t(14;18 (q32;q21). None found Not assessed
8
77
Incidental posthysterectomy for prolapse
IAE
Current case
Not given
IHC, immunohistochemistry.
376
J Clin Pathol April 2014 Vol 67 No 4
Downloaded from http://jcp.bmj.com/ on December 1, 2014 - Published by group.bmj.com
PostScript the endometrium, and a summary of all seven previously reported cases. Accurate histological interpretation is essential for distinguishing extranodal marginal zone lymphoma from reactive lymphoid aggregates and other B cell lymphomas to ensure optimal management. Anita J Merritt,1 Patrick Shenjere,2 Lia P Menasce,2 Fiona Reid,3 Tim Diss,4 Rhona J McVey,1 Richard J Byers1,5 1
Department of Histopathology, Manchester Royal Infirmary, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK 2 Department of Histopathology, The Christie NHS Foundation Trust, Manchester, UK 3 Department of Gynaecology, St Marys Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK 4 Department of Pathology, UCL-Advanced Diagnostics, University College London, London, UK 5 Institute of Cancer Sciences, The University of Manchester, Manchester, UK Correspondence to Dr Richard Byers, Department of Histopathology, Clinical Sciences Building One, Manchester Royal Infirmary, Oxford Road, Manchester M13 9WL, UK; [email protected] and [email protected] Contributors AJM wrote the manuscript. PS, LPM, RJMcV and RJB made the diagnosis and wrote the manuscript. FR provided clinical liaison and treated the patient. TD undertook scientific analysis detailed in the case report. Competing interests None. Patients Consent Obtained. Provenance and peer review Not commissioned; internally peer reviewed. To cite Merritt AJ, Shenjere P, Menasce L P, et al. J Clin Pathol 2014;67:375–377. Received 20 November 2013 Accepted 24 November 2013 Published Online First 18 December 2013 J Clin Pathol 2014;67:375–377. doi:10.1136/jclinpath-2013-202059
REFERENCES 1
2
3
4
5
6
Chorlton I, Karnei RF Jr, King FM, et al. Primary malignant reticuloendothelial disease involving the vagina, cervix, and corpus uteri. Obstet Gynecol 1974;44:735–48. Annibali O, Romeo AA, Agostinelli C, et al. A case of primary MALT lymphoma of the endometrium presenting as an asymptomatic polyp. Ann Hematol 2009;88:491–3. Heeren JHM, Croonen AM, Pijnenborg JMA. Primary extranodal marginal zone B-cell lymphoma of the female genital tract: a case report and literature review. Int J Gynecol Pathol 2008;27:243–6. Hamadani M, Kharfan-Dabaja M, Kamble R, et al. Marginal zone B-cell lymphoma of the uterus: a case report and review of the literature. J Okla State Med Assoc 2006;99:154–6. Frey NV, Svoboda J, Andreadis C, et al. Primary lymphomas of the cervix and uterus: the University of Pennsylvania’s experience and a review of the literature. Leuk Lymphoma 2006;47:1894–901. Iyengar P, Deodhare S. Primary extranodal marginal zone B-cell lymphoma of MALT type of the endometrium. Gynecol Oncol 2004;93:238–41.
J Clin Pathol April 2014 Vol 67 No 4
7
8
Ballesteros E, Osborne BM, Matsushima AY. CD5+ low-grade marginal zone B-cell lymphomas with localized presentation. Am J Surg Pathol 1998;22:201–7. Wright T, Rule S, Liu H, et al. Extranodal marginal zone lymphoma of the uterine corpus. Leuk Lymphoma 2012;53:1831–4.
Focal nodular hyperplasia-like lesion in a cirrhotic liver mimicking a cholangiocarcinoma INTRODUCTION Focal nodular hyperplasia (FNH) is a common benign liver lesion composed of nodules of proliferating hepatocytes, malformed vessels, and bile ductular proliferation. Classically, FNH has been reported in livers which are normal or near normal. Recently, however, FNH-like lesions have been reported in cirrhotic livers and, as such, FNH should be considered in the clinicopathologic differential diagnosis of hepatocellular carcinoma (HCC) and other nodular liver lesions.1–3 As most of these lesions are detected by imaging studies, it is useful to review the imaging characteristics of FNH. Classical FNH usually has typical imaging characteristics. On unenhanced scans, the lesion is homogenous and well defined and may be either hypo- or iso-dense. It shows bright enhancement on the early arterial phase before becoming iso-dense on the portal phase. The characteristic stellate central scar is hypo-dense on early arterial and portal phases before becoming hyperdense on delayed scans. This, however, is only seen in
