DISCUSSION

The proposed route for RSHM is the spread of malignant cells via the hepatic veins to caval venous system through the pulmonary circulation and then into arterial vessels.⁸ Once the malignant cells reach the arterial circulation, HCC metastasis may theoretically be found everywhere. To the best of our knowledge, this is the first report of the nail-bed as a HCC metastatic site. Kim et al¹⁷ described a case of a finger HCC metastasis, but it was another cutaneous HCC metastasis report. In their article, Kim et al reviewed six other finger location cases, but they were the more common cutaneous and bone HCC metastasis. Metastasis in the nail-bed are extremely rare. Only three cases can be found in the literature: from a rectal cancer,¹⁸ from renal carcinoma¹⁹ and from prostate cancer.²⁰

After analyzing the RSHM cases including ours (Table 1), we intended to answer the previous questions.

RSHM are observed mostly in HCCs at advanced stage at presentation (9 out of 14). One possible explanation for the RSHM observed in an early stage (I and II) HCC at presentation might be the presence of histological vascular invasion by the primary tumor. Of the four cases recorded, only Takahashi et al¹⁶ reported this finding, whereas it was unknown in the other three.

Elevation of PIVKA II is significantly more frequent in advanced stage HCCs.²¹ In keeping with that, PIVKA II was elevated in all the RSHM where its value was reported (Table 1).

Less than half of the RSHM reviewed received systemic therapy. Our case suggests that persistence in systemic treatments, even with little expected efficacy (such as capecitabine), may be important for longer survival.

Most of RSHM became clinically apparent within 1 year after the primary tumor diagnosis. In fact, 40% of RSHM were “true” synchronous (present at diagnosis). These facts may suggest that the spread of HCC through this unusual route for the appearance of RSHM seems to be an early event.

Besides, RSHM appear frequently (9 out of 15 cases) in the context of more common site metastasis, especially pulmonary metastasis.

Taken together these facts regarding RSHM presentation (in advanced stage cases, with elevated PIVKA-II, early and when other more usual location metastases are present) suggest a mechanism of early and diffuse systemic metastatic spread. At the same time, these data are contrary to the common notions that RSHM originate from more usual location metastasis in a stepwise fashion. Or that they are the consequence of a longer patient survival.^16,22

The Lee nomogram for prediction of extrahepatic metastasis in HCC² is reliable for RSHM high-risk patients at 1 year (all patients with RSHM). Nevertheless, is less reliable in RSHM low-risk patients (half of them had metastasis at 1 year). At 5 years, its reliability increases, as less RSHM low-risk patients have metastasis and more high-risk patients are affected.

Therefore, we propose that RSHM may be prevented with the earlier use of systemic treatments, especially in patients classified as “high risk” by the Lee nomogram.²

The median overall survival after RSHM diagnosis is only 5 months. RSHM are, as in our case, a final event with an ominous prognosis.

One of the strengths of our report is the awareness created after this new clinical description. All physicians in charge of HCC patients will be much more suspicious for RSHM. Especially for this new possibility, the nail-bed. Another strength is the collection of these rare cases in order to enunciate the main facts of RSHM. The main weakness of our article is the retrospective description and collection, with data lacking for a proper analysis. Obviously, rare cases always prevent from large series that could also power this analysis.

In conclusion, this new site case has allowed us to analyze the characteristics of the RSHM. This type of metastasis seems to be an early event, in the context of advanced stage HCC with elevated PIVKA II. The Lee nomogram is useful in classifying patients at high risk of developing RSHM. We may suggest insisting in systemic treatment in these metastatic patients although overall survival after RSHC diagnosis is poor.

Disclosure

The authors report no conflicts of interest in this work.

Enrique Boldo,¹ Ana Santafe,¹ Araceli Mayol,¹ Rafael Lozoya,¹ Alba Coret,¹ Diana Escribano,¹ Carlos Fortea-Sanchis,¹ Andres Muñoz,¹ Juan Carlos Pastor,¹ Guillermo Perez de Lucia,¹ Nuria Bosch²
¹Department of Surgery, Consorcio Hospitalario Provincial de Castellon, Castellon, Spain; ²Pathology Department, Consorcio Hospitalario Provincial de Castellon, Castellon, Spain
Correspondence: Enrique Boldo
Servicio de Cirugia, Consorcio Hospitalario Provincial de Castellon, Avenida Dr Clara 19, Castellon 12002 Tel +34-964359700
Fax +34-964354301
Email [email protected]

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Source: Journal of hepatocellular Carcinoma.
Originally published February 25, 2020.

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