Blue Blob-Like Bodies Mimicking Malignancy

Background: Incidental morphologic findings in lymph node tissue may represent a diagnostic challenge in surgical pathology. We have characterized, for the first time to our knowledge, dense globular structures that most likely represent degenerated lymphoid cells found in a Mascagni-Lund’s lymph node, and resemble Blue Blobs (Bbs) described in vaginal Papanicolaou-stained smears, or Hematoxylin Bodies (Hbs) commonly seen in patients diagnosed with Systemic Lupus Erythematosus (SLE), respectively. These Blue Blob-Like Bodies (Bbbs) are not associated with SLE, and immunohistochemistry may be necessary to rule out malignancy or viral infection. Objective: To characterize Blue Blob-Like Bodies (Bbbs) in a Mascagni-Lund’s lymph node from a cholecystectomy specimen performed for acute cholecystitis. Materials and Method: A paraffin-embedded cholecystectomy specimen that included a Mascagni-Lund’s lymph node was evaluated by routine microscopy in a busy surgical pathology service. Special stains, immunohistochemistry, and electron microscopy were performed to characterize the unusual structures observed. Results: Many scattered, round-to-oval, dense globular basophilic novel structures with smooth borders were identified and named Blue Blob-Like Bodies (Bbbs). Conclusion: Bbbs mimic malignant (primary or metastatic) or virally infected cells in lymph node tissue. However, they most likely represent degenerated lymphoid cells resulting from reactive lymphadenopathy secondary to acute cholecystitis.Pathologists need to recognize Bbbs and properly distinguish them from other pathological structures, in order to avoid misdiagnosis.


Introduction
Incidental morphologic findings in lymph node tissue may represent a diagnostic challenge in either benign or malignant surgical pathology. While malignancy could be primary or metastatic, the etiology of benign pathology ranges widely and includes infectious, inflammatory, and autoimmune disease. For instance, virally infected cells may be found serendipitously, especially in immunosuppressed patients. Similarly, various pathologic bodies have been described in different tissues, including lymph nodes. In 1932, Gross [1] described for the first time, amorphous extracellular deposits of basophilic material that could be stained with hematoxylin in patients with endocarditis due to Systemic Lupus Erythematosus (SLE). These structures, known as Hematoxylin Bodies (Hbs), are considered highly specific for SLE. In 1959, Pollack [2] recognized Hbs in lupus lymphadenitis.
Soon after, Candreviotis [3] described Hbs-like material in nodal tissue from a patient with Classical Hodgkin Lymphoma, a finding which has not been reproduced yet. In addition, Handra-Luca et al. [4] noted the presence of lipogranulomata in a sentinel gall bladder lymph node (Mascagni's or Lund's node), which may morphologically suggest metastatic signet ring adenocarcinoma.
Therefore, characterization of unique structures that could be confused with atypical cells (malignant or virally infected) or known pathologic bodies remains significant. For example, the so-called blue blobs (Bbs) described by Milligan et al. [5] may be a source of misdiagnosis in postmenopausal vaginal smears, since they simulate malignancy. Likewise, a few structures such as crystals or Liesegang rings have been confused with parasitic organisms and may be associated with malignancy [6,7]. Herein, we describe previously unrecognized atypical material in a Mascagni-Lund's lymph node from a specimen obtained after cholecystectomy for acute cholecystitis.

Results
Hematoxylin and Eosin (H&E) stained sections from paraffinembedded tissue revealed a small lymph node with preserved architecture and follicle lysis, containing naked germinal centers.
Scattered round-to-oval dense globular basophilic structures with smooth borders, resembling cells with large atypical nuclei and high Nuclear/Cytoplasmic (N/C) ratio, were identified in the interfollicular areas and sinuses (Figure 1). These non-polarizable structures were suspicious for malignancy or viral infection.
Morphologically they best resemble blue blobs (Bbs), as delineated by Abdulla et al. [8] and are henceforth referred to as blue bloblike bodies (Bbbs). Bbbs varied in size from 5-30 μ, and showed homogenous dark blue color and somewhat coarse texture     respectively.Also, Bbbs could be mistaken for Hematoxylin Bodies (Hbs) since both contain degenerated nuclear material, as proven by positive Feulgen staining. However, significant differences between these two structures exist. For example, Hbs are typically found in patients with SLE, [3,9] although a single report described them in association with Hodgkin Disease [3]. Nevertheless, the illustrations of Hbs in this historic publication have been considered unconvincing, [9] and therefore, the strong association of Hbs and SLE remains valid. Interestingly, our patient does not have current or past medical history of SLE, other autoimmune disease, or malignancy. Moreover, Hbs are commonly present in necrotic tissue including necrotizing lymphadenitis, [10] but necrosis was absent in the gallbladder neck lymph node analyzed here. Furthermore, on H&E stains, Hbs display larger size, more angulated shape, and rougher edges than Bbbs, which are smaller, smoother, and rounder.
Finally, Hbs are amphophilic (magenta color) on Romanowsky-type stains, while Bbbs are basophilic. Consequently, although Hbs and Bbbs may both represent cellular degeneration, they are dissimilar.
In summary, Bbbs are novel DNA-rich globular structures, which seem to represent degenerated lymphoid cells resulting from reactive lymphadenopathy secondary to acute cholecystitis. Bbbs