Carcinoma and multiple lymphomas in one patient: establishing the diagnoses and analyzing risk factors

Abstract

Multiple malignancies may occur in the same patient, and a few reports describe cases with multiple hematologic and non-hematologic neoplasms. We report the case of a patient who showed the sequential occurrence of four different lymphoid neoplasms together with a squamous cell carcinoma of the lung. A 62-year-old man with adenopathy was admitted to the hospital, and lymph node biopsy was positive for low-grade follicular lymphoma. He achieved a partial remission with chemotherapy. Two years later, a PET-CT scan showed a left hilar mass in the lung; biopsy showed a squamous cell carcinoma. Simultaneously, he was diagnosed with diffuse large B cell lymphoma in a neck lymph node; after chemo- and radiotherapy, he achieved a complete response. A restaging PET-CT scan 2 years later revealed a retroperitoneal nodule, and biopsy again showed a low-grade follicular lymphoma, while a biopsy of a cutaneous scalp lesion showed a CD30-positive peripheral T cell lymphoma. After some months, a liver biopsy and a right cervical lymph node biopsy showed a CD30-positive peripheral T cell lymphoma consistent with anaplastic lymphoma kinase-negative anaplastic large cell lymphoma. Flow cytometry and cytogenetic and molecular genetic analysis performed at diagnosis and during the patient's follow-up confirmed the presence of two clonally distinct B cell lymphomas, while the two T cell neoplasms were confirmed to be clonally related. We discuss the relationship between multiple neoplasms occurring in the same patient and the various possible risk factors involved in their development.

Keywords: Anaplastic large cell lymphoma; Cytogenetics; Diffuse large B cell lymphoma; Follicular lymphoma; Multiple malignancies; Risk factors.

Fig. 1

Cytogenetic analysis of the patient's B cell lymphomas. Cytogenetic analysis of the 2003 lymph node showing grade 1 follicular lymphoma (a) revealed a complex karyotype (arrows), with a translocation between chromosomes 14 and 18 indicating a rearrangement involving IGH and BCL2. Analysis of the 2006 lymph node with DLBCL also showed a complex karyotype (arrows), which was distinct from that of the prior follicular lymphoma (b). In particular, t(14;18) was absent. Metaphase FISH analysis revealed a BCL6 rearrangement involving chromosome 3 (not shown). For complete karyotypes, see Table 2

Fig. 2

Histologic and immunohistochemical findings of the patient's B cell lymphomas. Biopsy of enlarged left neck lymph node from 2006 revealed an infiltrate of large atypical lymphoid cells with oval, irregular, and multilobated nuclei and prominent nucleoli (a). The cells effaced the nodal architecture in a diffuse pattern (b) and were positive for Pax5 (c), consistent with DLBCL. In 2008, a retroperitoneal lymph node core biopsy showed a proliferation of small lymphocytes with irregular nuclei, consistent with centrocytes (d), forming vague follicle structures (e) and staining positively for Pax5 (f). The findings were consistent with relapsed follicular lymphoma, grade 1 of 3

Fig. 3

Histologic and immunohistochemical findings of the patient’s T cell lymphomas. In 2008, biopsy of an enlarged right neck lymph node showed a diffuse proliferation of large atypical lymphoid cells with round to irregular nuclei, sometimes reniform nuclei; mitotic figures were readily apparent (a). The tumor cells were positive for CD3 (b), strongly positive for CD30 (c), and negative for ALK-1 (not shown). A diagnosis of ALCL, ALK negative was made. Eight months earlier, biopsy of the patient’s 2008 scalp lesion revealed a dense dermal infiltrate of large atypical lymphoid cells with irregular nuclei (d). The infiltrate extended to involve subcutaneous tissue and was positive for CD3 (e) and CD30 (f) and negative for ALK-1 (not shown). Subsequent TCR gene rearrangement studies supported that the prior skin biopsy represented secondary cutaneous involvement by a systemic ALK-negative ALCL

Fig. 4

Molecular genetic studies of the patient’s B cell lymphomas. IgH gene rearrangement studies on both the 2008 lymph node showing grade 1 follicular lymphoma (a and c) and the 2006 lymph node showing DLBCL (b and d) revealed clonal B cell populations. In the 2008 case, the clonal IgH gene rearrangement was detected with PCR primers to framework region I only (a, 319 bp), whereas primers to framework region II (c) showed a polyclonal B cell population. In contrast, in the 2006 case, the clonal rearrangement was detected with primers to both framework regions I (a, 323 bp) and II (d, 267 bp), indicating that the two lymphomas arose from different primaries. Framework region III primers were polyclonal in both samples (not shown)